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Background and Objective: Lung cancer stands as the main cause of cancer-related deaths worldwide. With the advent of immunotherapy and the discovery of targetable oncogenic driver genes, although prognosis has changed in the last few years, survival rates remain dismal for most patients. This emphasizes the urgent need for new strategies that could enhance treatment in precision medicine. The role of the microbiota in carcinogenesis constitutes an evolving landscape of which little is known. It has been suggested these microorganisms may influence in responses, resistance, and adverse effects to cancer treatments, particularly to immune checkpoint blockers. However, evidence on the impact of microbiota composition in oncogene-addicted tumors is lacking. This review aims to provide an overview of the relationship between microbiota, daily habits, the immune system, and oncogene-addicted tumors, focusing on lung cancer. Methods: A PubMed and Google Scholar search from 2013 to 2024 was conducted. Relevant articles were reviewed in order to guide our research and generate hypothesis of clinical applicability. Key Content and Findings: Microbiota is recognized to participate in immune reprogramming, fostering inflammatory, immunosuppressive, or anti-tumor responses. Therefore, identifying the microbiota that impact response to treatment and modulating its composition by interventions such as dietary modifications, probiotics or antibiotics, could potentially yield better outcomes for cancer patients. Additionally, targeted therapies that modulate molecular signaling pathways may impact both immunity and microbiota. Understanding this intricate interplay could unveil new therapeutic strategies. Conclusions: By comprehending how microbiota may influence efficacy of targeted therapies, even though current evidence is scarce, we may generate interesting hypotheses that could improve clinical practice.

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The training of hospital pharmacists in the coming years must adapt and respond to constant current and future social and technological challenges, without neglecting the basic areas of the profession. It is necessary to acquire knowledge in what is known as digital comprehensive health: Artificial intelligence, technology and automation, digital skills, and new forms of communication with patients, such as telemedicine and telepharmacy that are already a reality in many hospitals. We must provide knowledge in automated systems for the distribution and dispensing of medicines, robots for preparing sterile preparations, traceability systems, the use of drones in clinical care, etc., as well as including training in the application of technology in pharmaceutical care, through devices and applications that help identify patients who require specific care early and effectively. In this digital scenario, new risks and challenges must be faced, such as cybersecurity and cyber-resilience, which makes the training and education of healthcare professionals in general, and hospital pharmacists in particular, essential. On the other hand, the appearance of increasingly complex and innovative therapies has a great impact not only on health population but also on economic and environmental issues, which makes new competencies and skills essential to develop and implement disruptive and competent financing, equity, and sustainability strategies. In this demanding and hyper-connected environment, it is understandable that the well-known "burned out worker syndrome" appears, which prevents the correct personal and professional development of the team and highlights the importance of quality training for its prevention and management. In short, in the next decade, the training of hospital pharmacists must be aimed at providing knowledge in innovation and in basic skills needed to adapt and succeed to current demands and changes.

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The training of hospital pharmacists in the coming years must adapt and respond to constant current and future social and technological challenges, without neglecting the basic areas of the profession. It is necessary to acquire knowledge in what is known as digital comprehensive health: artificial intelligence, technology and automation, digital skills, and new forms of communication with patients, such as telemedicine and telepharmacy that are already a reality in many hospitals. We must provide knowledge in automated systems for the distribution and dispensing of medicines, robots for preparing sterile preparations, traceability systems, the use of drones in clinical care, etc. as well as training in the application of technology in pharmaceutical care, through devices and applications that help identify patients who require specific care early and effectively. In this digital scenario, new risks and challenges must be faced, such as cybersecurity and cyber resilience, which makes the training and education of healthcare professionals in general, and hospital pharmacists in particular, inexcusable. On the other hand, the appearance of increasingly complex and innovative therapies has a great impact not only on health population but also on economic and environmental issues, which makes new competencies and skills essential to develop and implement disruptive and competent financing, equity, and sustainability strategies. In this demanding and hyper-connected environment, it is understandable that the well-known "burned out worker syndrome" appears, which prevents the correct personal and professional development of the team and highlights the importance of quality training for its prevention and management. In short, in the next decade, the training of hospital pharmacists must be aimed at providing knowledge in innovation and in basic skills needed to adapt and succeed to current demands and changes.

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Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite's remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease.

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The level of airway constriction in thin slices of lung tissue is highly variable. Owing to the labor-intensive nature of these experiments, determining the number of airways to be analyzed in order to allocate a reliable value of constriction in one mouse is challenging. Herein, a new automated device for physiology and image analysis was used to facilitate high throughput screening of airway constriction in lung slices. Airway constriction was first quantified in slices of lungs from male BALB/c mice with and without experimental asthma that were inflated with agarose through the trachea or trans-parenchymal injections. Random sampling simulations were then conducted to determine the number of airways required per mouse to quantify maximal constriction. The constriction of 45 ± 12 airways per mouse in 32 mice were analyzed. Mean maximal constriction was 37.4 ± 32.0%. The agarose inflating technique did not affect the methacholine response. However, the methacholine constriction was affected by experimental asthma (p = 0.003), shifting the methacholine concentration-response curve to the right, indicating a decreased sensitivity. Simulations then predicted that approximately 35, 16 and 29 airways per mouse are needed to quantify the maximal constriction mean, standard deviation and coefficient of variation, respectively; these numbers varying between mice and with experimental asthma.

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Human gut microbial metabolites are currently undergoing much research due to their involvement in multiple biological processes that are important for health, including immunity, metabolism, nutrition, and the nervous system. Metabolites exert their effect through interaction with host and bacterial proteins, suggesting the use of "metabolite-mimetic" molecules as drugs and nutraceutics. In the present work, we retrieve and analyze the full set of published interactions of these compounds with human and microbiome-relevant proteins and find patterns in their structure, chemical class, target class, and biological origins. In addition, we use virtual screening to expand (more than 4-fold) the interactions, validate them with retrospective analyses, and use bioinformatic tools to prioritize them based on biological relevance. In this way, we fill many of the chemobiological gaps observed in the published data. By providing these interactions, we expect to speed up the full clarification of the chemobiological space of these compounds by suggesting many reliable predictions for fast, focused experimental testing.

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In the present work, we study different physicochemical properties related to LADME processes of volasertib, a Polo-like kinase 1 inhibitor in advanced clinical trials. Firstly, the protonation equilibria, the extent of ionization at the physiological pH and pKa values of this drug are studied combining spectroscopic techniques and computational calculations. Secondly, the binding process of volasertib to the human serum albumin (HSA) protein is analyzed by fluorescence spectroscopy. We report a high binding constant to HSA (Ka = 4.10 × 106 M-1) and their pharmacokinetic implications are discussed accordingly. The negative enthalpy and entropy (ΔH0 = -54.49 kJ/mol; ΔS0 = -58.90 J K-1 mol-1) determined for the binding process suggests the implication of hydrogen bonds and van der Waals interactions in the formation of the HSA-volasertib complex. Additionally, volasertib is encapsulated in an alginate/montmorillonite bionanocomposite as a proof of concept for an oral delivery nanocarrier. The physical properties of that nanocomposite as well as volasertib delivery kinetics are analyzed.

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The development of new fluorescent probes as molecular sensors is a critical step for the understanding of molecular mechanisms. BODIPY-based probes offer versatility due to their high fluorescence quantum yields, photostability, and tunable absorption/emission wavelengths. Here, we report the synthesis and evaluation of a novel 7-azaindole-BODIPY derivative to probe hydrophobic proteins as well as protein misfolding and aggregation. In organic solvents, this compound shows two efficiently interconverting emissive excited states. In aqueous environments, it forms molecular aggregates with unique photophysical properties. The complex photophysics of the 7-azaindole-BODIPY derivative was explored for sensing applications. In the presence of albumin, the compound is stabilized in hydrophobic protein regions, significantly increasing its fluorescence emission intensity and lifetime. Similar effects occur in the presence of protein aggregates but not with other macromolecules like pepsin, DNA, Ficoll 40, and coconut oil. Fluorescence lifetime imaging microscopy (FLIM) and two-photon fluorescence microscopy on breast (MCF-7) and lung (A549) cancer cells incubated with this compound display longer fluorescence lifetimes and higher emission intensity under oxidative stress. Synchrotron FTIR micro spectroscopy confirmed that the photophysical changes observed were due to protein misfolding and aggregation caused by the oxidative stress. These findings demonstrate that this compound can serve as a fluorescent probe to monitor protein misfolding and aggregation triggered by oxidative stress.

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BACKGROUND: Disparities secondary to underinsurance present throughout the surgical care continuum. Community free clinics are uniquely capable to provide health care services to the medically underserved, but surgery often falls outside their scope of care. METHODS: Retrospective chart review was conducted on consecutive community free clinic patients receiving free surgical services via referral to a partnering ambulatory surgery center between March 2016 and September 2021. Those with documented contact information were recruited 1-3 years post-procedure for long-term quality-of-life (LTQOL) outcomes assessment via modified Veterans RAND 12-item health survey. RESULTS: Of 142 included patients, 95.7% identified as Hispanic/Latino and 75.6% were uninsured. Twelve patients had cancerous or precancerous lesions detected and/or removed through diagnostic or definitive procedures. 3.5% experienced postoperative complication including bacterial (n = 2) or fungal (n = 1) surgical site infection and wound dehiscence (n = 2). With a 48.9% response rate, no significant differences in sociodemographic or clinical characteristics were found between surveyed vs non-surveyed patients. Of surveyed patients, 59.7% and 52.2% reported pre-/post-operative improvement in physical health and emotional health, respectively. DISCUSSION: Free diagnostic screening procedures provided timely diagnoses while free definitive surgeries safely and positively impacted long-term patient-reported physical health. Longitudinal, multidisciplinary follow-up and social support may be warranted to concurrently improve emotional and mental health in similarly underinsured populations.

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PURPOSE: Air trapping, often attested in humans by elevated residual volume (RV) and ratio of RV on total lung capacity (RV/TLC), is frequently observed in asthma. Confirming these alterations in experimental asthma would be important for translational purposes. Herein, lung volumes were investigated in a mouse model of pulmonary allergic inflammation. METHODS: Eight- to 10-week-old male C57BL/6 and BALB/c mice were exposed once daily to intranasal house dust mite (HDM) for 10 consecutive days. All readouts were measured 24 h after the last exposure. Lung volumes were assessed with the flexiVent using a new automated method consisting of degassing the lungs followed by a full-range pressure-volume maneuver. The weight and the volume of the lungs were also measured ex vivo and a lobe was further processed for histological analyses. RESULTS: HDM exposure led to tissue infiltration with inflammatory cells, goblet cell hyperplasia, thickening of the airway epithelium, and elevated ex vivo lung weight and volume. It also decreased TLC and vital capacity but without affecting RV and RV/TLC. These observations were similar between the two mouse strains. CONCLUSION: Alterations of lung volumes in a murine model of pulmonary allergic inflammation are inconsistent with observations made in human asthma. These discrepancies reflect the different means whereby lung volumes are measured between species. The invasive method used herein enables RV to be measured more precisely and without the confounding effect of air trapping, suggesting that changes in RV and RV/TLC using this method in mice should be interpreted differently than in humans.

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OBJECTIVE: This article describes a study protocol for evaluating adherence to oral chemotherapy (OCT) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in Spain. METHODS: This multicenter, observational, prospective study will be conducted by 6 hospital pharmacists from 6 Spanish hospitals. The study will include men and women aged 18 years or older with a diagnosis of locally advanced or metastatic NSCLC who are being treated or have been prescribed OCT. Once included, the patient will be active and prospectively followed up for 3 months, including 4 study visits to record information on sociodemographic variables, antineoplastic treatment and adherence, pharmaceutical care, clinical variables, and patient-reported outcomes (PRO) (the 3-level version of EQ-5D, the EORTC Core Quality of Life Questionnaire, the Brief Illness Perception Questionnaire, the Treatment Satisfaction with Medicines Questionnaire, and the PRO version of Common Terminology Criteria for Adverse Events). Twelve months after patient inclusion, we will record information on the disease progression status and dispensed prescriptions. The primary outcome is the percentage of treatment adherence that will be calculated based on the pill count as follows: the difference between the number of pills dispensed minus the number of unused pills will be divided by the number of days of treatment multiplied by the number of pills/day prescribed by the oncologist; this quotient will be multiplied by 100 to obtain the percentage of adherence. Based on the that pill count reconciliation, those with a percentage adherence >80% will be primarily categorized as adherent. Secondarily, treatment adherence will be also calculated based on the proportion of days covered and the 4-items Morisky Green Levine Medication Adherence Scale. To analyze the impact of patients' and treatment characteristics on adherence, bivariate analyses will be performed using different adherence cut-off points. To evaluate the impact of adherence on treatment efficacy as evaluated by progression-free survival, we will be using the Kaplan-Meier method and compare it with the log-rank test and univariate Cox regression analysis. CONCLUSIONS: We expect that our study will provide initial information on key aspects of adherence to OCT (i.e., measurement, facilitators, and barriers) and its relationship with patients' and clinically relevant outcomes in the setting of NSCLC, and that this information will help in designing pharmaceutical interventions to improve adherence.

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The effective measurement of temperature in living systems at the nano and microscopic scales continues to be a challenge to this day. Here, we study the use of 2-(anthracen-2-yl)-1,3-diisopropylguanidine, 1, as a nanothermometer based on fluorescence lifetime measurements and its bioimaging applications. In aqueous solution, 1 is shown in aggregated form and the equilibrium between the two main aggregate types (T-shaped and π-π) is highly sensitive to the temperature. The heating of the medium shifts the equilibrium toward the formation of highly emissive T-shaped aggregates. This species shows a high fluorescence emission and a long lifetime in comparison with the π-π aggregates and the freé monomer. A linear relationship between the fluorescence lifetime and the temperature both in aqueous solution and in a synthetic intracellular buffer was found. Fluorescence lifetime imaging microscopy (FLIM) also showed a linear relationship between lifetime and temperature with an excellent sensitivity in MCF7 breast cancer cells, which opens the door for its potential use as FLIM nanothermometer in the biomedical field.

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Objetivo: aportar evidencia de la efectividad de certolizumab pegol (CZP) en la práctica clínica real en pacientes adultos afectados por psoriasis (PsO) en placas moderada-grave, dentro del contexto de un acuerdo de riesgo compartido (ARC). Métodos: estudio observacional retrospectivo a partir de las variables recogidas en un ARC en los pacientes adultos con PsO en placas moderada-grave tratados con CZP. Participaron 10 hospitales españoles donde se estableció el ARC. Se evaluó el porcentaje de pacientes que alcanzaron la respuesta clínica objetivo del ARC en la visita de seguimiento (semana 16): valor de Psoriasis Area and Severity Index (PASI) absoluto ≤3 para la población naive a biológicos, y ≤5 ante el fracaso previo a un único fármaco biológico. Además, se analizó la mejora en la puntuación de otras escalas: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician’s Global Assesment (PGA) y Nail Psoriasis Severity Index (NAPSI). Se realizó un análisis descriptivo del total de la población y por subgrupos de pacientes (naive vs. no naive a biológico, hombre vs. mujer, y con vs. sin interrupción). Resultados: se incluyeron 66 pacientes, 12 hombres y 54 mujeres. El 90,9% alcanzaron la respuesta clínica objetivo, con una reducción media de 8 (−78,4%) puntos de PASI absoluto. Se observó una mejora en BSA, PGA, NAPSI y DLQI, con una reducción de 11,3 (−80,6%), 1,9 (−65,5%), 3,3 (−30,7%) y 9,0 (−66,4%) puntos del valor absoluto, respectivamente. Pese a no alcanzar el objetivo terapéutico establecido en el ARC en 6 pacientes (9%) (el coste del fármaco fue asumido por el laboratorio), solo 2 (3%) interrumpieron el tratamiento. Conclusión: nuestro estudio muestra que CZP resulta efectivo en la práctica clínica real en los pacientes con PsO en placas moderada-grave con una mejora de PASI absoluto y DLQI, así como de otras escalas, tanto para el total de la población como en los subgrupos analizados...(AU)

Objective: To provide evidence of the effectiveness of certolizumab pegol (CZP) in real clinical practice in adult patients with moderate-to-severe plaque psoriasis (PsO) in the context of a risk-sharing agreement (RSA). Methods: Retrospective observational study based on variables collected in the RSA for treatment with CZP of adult patients with moderate-severe plaque PsO. Ten Spanish hospitals where the RSA was implemented participated. The percentage of patients who achieved the target clinical response of the RSA at the follow-up visit (week 16) was evaluated: absolute Psoriasis Area and Severity Index (PASI) value ≤3 for biologic naïve population, and ≤5 in case of previous failure to a single biologic drug. In addition, the improvement in the scores of other scales included in the study was analyzed: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and Nail Psoriasis Severity Index (NAPSI). A descriptive analysis was performed for the total population and by patient subgroups (naive vs. non-naive to biologic, male vs. female, and with vs. without discontinuation). Results: Sixty-six patients were included, 12 men and 54 women. 90.9% achieved the target clinical response, with a mean reduction of 8 (−78.4%) absolute PASI points. Improvement was observed in BSA, PGA, NAPSI and DLQI, with a reduction of 11.3 (−80.6%), 1.9 (−65.5%), 3.3 (−30.7%) and 9.0 (−66.4%) absolute value points, respectively. Despite not achieving the therapeutic target set in the RSA in six patients (9%) (the cost of the drug was assumed by the laboratory), only two (3%) discontinued treatment. Conclusion: Our study shows that CZP is effective in real clinical practice in patients with moderate-severe plaque PsO, with an improvement in absolute PASI and DLQI, as well as other scales, both for the total population and in the subgroups analyzed. Nearly 91% of patients reached the therapeutic target fixed in the RSA...(AU)

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Objetivo: aportar evidencia de la efectividad de certolizumab pegol (CZP) en la práctica clínica real en pacientes adultos afectados por psoriasis (PsO) en placas moderada-grave, dentro del contexto de un acuerdo de riesgo compartido (ARC). Métodos: estudio observacional retrospectivo a partir de las variables recogidas en un ARC en los pacientes adultos con PsO en placas moderada-grave tratados con CZP. Participaron 10 hospitales españoles donde se estableció el ARC. Se evaluó el porcentaje de pacientes que alcanzaron la respuesta clínica objetivo del ARC en la visita de seguimiento (semana 16): valor de Psoriasis Area and Severity Index (PASI) absoluto ≤3 para la población naive a biológicos, y ≤5 ante el fracaso previo a un único fármaco biológico. Además, se analizó la mejora en la puntuación de otras escalas: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician’s Global Assesment (PGA) y Nail Psoriasis Severity Index (NAPSI). Se realizó un análisis descriptivo del total de la población y por subgrupos de pacientes (naive vs. no naive a biológico, hombre vs. mujer, y con vs. sin interrupción). Resultados: se incluyeron 66 pacientes, 12 hombres y 54 mujeres. El 90,9% alcanzaron la respuesta clínica objetivo, con una reducción media de 8 (−78,4%) puntos de PASI absoluto. Se observó una mejora en BSA, PGA, NAPSI y DLQI, con una reducción de 11,3 (−80,6%), 1,9 (−65,5%), 3,3 (−30,7%) y 9,0 (−66,4%) puntos del valor absoluto, respectivamente. Pese a no alcanzar el objetivo terapéutico establecido en el ARC en 6 pacientes (9%) (el coste del fármaco fue asumido por el laboratorio), solo 2 (3%) interrumpieron el tratamiento. Conclusión: nuestro estudio muestra que CZP resulta efectivo en la práctica clínica real en los pacientes con PsO en placas moderada-grave con una mejora de PASI absoluto y DLQI, así como de otras escalas, tanto para el total de la población como en los subgrupos analizados...(AU)

Objective: To provide evidence of the effectiveness of certolizumab pegol (CZP) in real clinical practice in adult patients with moderate-to-severe plaque psoriasis (PsO) in the context of a risk-sharing agreement (RSA). Methods: Retrospective observational study based on variables collected in the RSA for treatment with CZP of adult patients with moderate-severe plaque PsO. Ten Spanish hospitals where the RSA was implemented participated. The percentage of patients who achieved the target clinical response of the RSA at the follow-up visit (week 16) was evaluated: absolute Psoriasis Area and Severity Index (PASI) value ≤3 for biologic naïve population, and ≤5 in case of previous failure to a single biologic drug. In addition, the improvement in the scores of other scales included in the study was analyzed: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and Nail Psoriasis Severity Index (NAPSI). A descriptive analysis was performed for the total population and by patient subgroups (naive vs. non-naive to biologic, male vs. female, and with vs. without discontinuation). Results: Sixty-six patients were included, 12 men and 54 women. 90.9% achieved the target clinical response, with a mean reduction of 8 (−78.4%) absolute PASI points. Improvement was observed in BSA, PGA, NAPSI and DLQI, with a reduction of 11.3 (−80.6%), 1.9 (−65.5%), 3.3 (−30.7%) and 9.0 (−66.4%) absolute value points, respectively. Despite not achieving the therapeutic target set in the RSA in six patients (9%) (the cost of the drug was assumed by the laboratory), only two (3%) discontinued treatment. Conclusion: Our study shows that CZP is effective in real clinical practice in patients with moderate-severe plaque PsO, with an improvement in absolute PASI and DLQI, as well as other scales, both for the total population and in the subgroups analyzed. Nearly 91% of patients reached the therapeutic target fixed in the RSA...(AU)

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Background: Intravenous (IV) contrast improves the sensitivity and specificity of injury detection in computerized tomography (CT). Its use is recommended in the workup of trauma patients by the American College of Surgeons and American College of Radiology. On May 9, 2022, the Food and Drug Administration declared a shortage of iodinated contrast due to the COVID-19 pandemic. Although the shortage has ended, the temporary lack of IV contrast forced physicians to be prudent in ordering CT scans with IV contrast. We sought to determine if there was a change in the percentage of CT contrast studies performed during the contrast shortage and if this change affected patient outcomes.Methods: Retrospective chart review was performed on all adult tier 2 trauma patients at a 619-bed community-based level II trauma center who received CT chest, abdomen, and pelvis imaging as initial workup for blunt trauma from 5/9/2021-6/30/2021 (pre-shortage) and 5/9/2022-6/30/2022 (during shortage).Results: Patients were predominantly male with median age of 31-52 and of White or Hispanic ethnicity. Before the contrast shortage, all 110 trauma patients were scanned with contrast. During the shortage, 29 of 114 patients were scanned with contrast (P < 0.001). Injuries were identified in 59% of patients scanned with contrast (P < 0.001). There were no significant differences in blood transfusion needs, repeat CT, disposition, or mortality when comparing pre-shortage to during shortage or when comparing between non-contrast and contrast studies during the shortage.Discussion: There was a decrease in the percentage of CT contrast studies performed during the shortage. A higher percentage of injuries were identified in the patients scanned with contrast. However, there were no significant differences in patient outcomes. Certain trauma patients may be safely scanned without contrast.

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Eight pig tracheal strips were stimulated to contract with log increments of methacholine from 10-8 to 10-5 M. For each strip, the concentration-response was repeated four times in a randomized order to measure isometric force, isotonic shortening against a load corresponding to either 5 or 10 % of a reference force, and average force, stiffness, elastance and resistance over one cycle while the strip length was oscillating sinusoidally by 5 % at 0.2 Hz. For each readout, the logEC50 was calculated and compared. Isotonic shortening with a 5 % load had the lowest logEC50 (-7.13), yielding a greater sensitivity than any other contractile readout (p<0.05). It was followed by isotonic shortening with a 10 % load (-6.66), elastance (-6.46), stiffness (-6.46), resistance (-6.38), isometric force (-6.32), and average force (-6.30). Some of these differences were significant. For example, the EC50 with the average force was 44 % greater than with the elastance (p=0.001). The methacholine sensitivity is thus affected by the contractile readout being measured.

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5P medicine is defined as Personalized, Predictive, Preventive, Participatory, and Population-based. 5P medicine may be improved by including a factor that could provide information about the therapeutic value of a particular drug treatment and measure its effectiveness in clinical practice. We propose that this factor may be treatment persistence, and that its addition to 5P medicine would allow to define a new improved 6P medicine. Persistence is the length of time between initiation and the last dose, which immediately precedes discontinuation, that is, a definitive suspension of the treatment. By including this sixth P, the persistence, we would be able to present the value of a treatment for each individual patient with its own characteristics, state of the disease, with more than one age-related diseases and patient journey. Persistence is a concept of the value of a treatment that includes the three main stakeholders of the pharmacotherapeutic process: Patient, Physician, and Pharmacist. Persistence is becoming a useful measure to evaluate the long-term effectiveness of therapies in real-world setting in chronic diseases. Drug treatments with longer persistence are more likely to provide better disease control and to be amenable to dose adjustment in order to optimize treatment cost in age-related chronic diseases. Long-term persistence could be a measure of a drug´s real-world performance and has been shown to aid in clinical decision-making.

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BACKGROUND: Implementing mammogram screening means that clinicians are seeing many breast cancers that will never develop metastases. The purpose of this study was to identify subgroups of breast cancer patients who did not present events related to long-term breast cancer mortality, taking into account diagnosis at breast screening, absence of palpability and axillary involvement, and genomic analysis with PAM50. PATIENTS AND METHODS: To identify them, a retrospective observational study was carried out selecting patients without any palpable tumor and without axillary involvement, and a genomic analysis was performed with PAM50. RESULTS: The probability of distant metastasis-free interval (DMFI) of 337 patients was 0.92 (95% CI, 0.90-0.93) at 20 years and 0.96 (95% CI, 0.92-1.00) in 95 patients (28%) with available PAM50 tests. In 22 (23.15%) luminal A tumors and in 9 (9.47%) luminal B tumors smaller than 1 cm, and in HER2 and basal type tumors, there were no metastatic events (20-year DMFI of 1.00). CONCLUSION: Patients with nonpalpable breast cancer found at screening with negative nodes are at very low risk. It is possible to identify subgroups without metastatic events by determining the intrinsic subtype and tumor size less than 1 cm. Therefore, de-escalation of treatment should be considered.