Acetazolamide encapsulation in elastin like recombinamers using a supercritical antisolvent (SAS) process for glaucoma treatment.

Glaucoma, the second most common cause of blindness worldwide, requires the development of new and effective treatments. This study introduces a novel controlled-release system utilizing elastin-like recombinamers (ELR) and the Supercritical Antisolvent (SAS) technique with supercritical CO2. Acetazolamide (AZM), a class IV drug with limited solubility and permeability, is successfully encapsulated in an amphiphilic ELR at three different ELR:AZM ratios, yielding up to 62 %. Scanning electron microscopy (SEM) reveals spherical microparticles that disintegrate into monodisperse nanoparticles measuring approximately 42 nm under physiological conditions. The nanoparticles, as observed via Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), do not exhibit aggregates, a fact confirmed by the zeta potential displaying a value of -33 mV over a period of 30 days. Transcorneal permeation tests demonstrate a 10 % higher permeation level compared to the control solution, which increases to 30 % after 2 h. Ocular irritation tests demonstrate no adverse effects or damage. Intraocular pressure (IOP) tests conducted on hypertensive rabbits indicate greater effectiveness for all three analyzed formulations, suggesting enhanced drug bioavailability during treatment. Consequently, the combination of recombinant biopolymers and high-pressure techniques represents a promising approach for advancing glaucoma therapy, emphasizing its potential clinical significance.

Autophagy sustains mitochondrial respiration and determines resistance to BRAFV600E inhibition in thyroid carcinoma cells.

BRAFV600E is the most prevalent mutation in thyroid cancer and correlates with poor prognosis and therapy resistance. Although selective inhibitors of BRAFV600E have been developed, more advanced tumors such as anaplastic thyroid carcinomas show a poor response in clinical trials. Therefore, the study of alternative survival mechanisms is needed. Since metabolic changes have been related to malignant progression, in this work we explore metabolic dependencies of thyroid tumor cells to exploit them therapeutically. Our results show that respiration of thyroid carcinoma cells is highly dependent on fatty acid oxidation and, in turn, fatty acid mitochondrial availability is regulated through macroautophagy/autophagy. Furthermore, we show that both lysosomal inhibition and the knockout of the essential autophagy gene, ATG7, lead to enhanced lipolysis; although this effect is not essential for survival of thyroid carcinoma cells. We also demonstrate that following inhibition of either autophagy or fatty acid oxidation, thyroid tumor cells compensate oxidative phosphorylation deficiency with an increase in glycolysis. In contrast to lipolysis induction, upon autophagy inhibition, glycolytic boost in autophagy-deficient cells is essential for survival and, importantly, correlates with a higher sensitivity to the BRAFV600E selective inhibitor, vemurafenib. In agreement, downregulation of the glycolytic pathway results in enhanced mitochondrial respiration and vemurafenib resistance. Our work provides new insights into the role of autophagy in thyroid cancer metabolism and supports mitochondrial targeting in combination with vemurafenib to eliminate BRAFV600E-positive thyroid carcinoma cells.Abbreviations: AMP: adenosine monophosphate; ATC: anaplastic thyroid carcinoma; ATG: autophagy related; ATP: adenosine triphosphate; BRAF: B-Raf proto-oncogene, serine/threonine kinase; Cas9: CRISPR-associated protein; CREB: cAMP responsive element binding protein; CRISPR: clustered regularly interspaced short palindromic repeats; 2DG: 2-deoxyglucose; FA: fatty acid; FAO: fatty acid oxidation; FASN: fatty acid synthase; FCCP: trifluoromethoxy carbonyl cyanide phenylhydrazone; LAMP1: lysosomal associated membrane protein 1; LIPE/HSL: lipase E, hormone sensitive type; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OCR: oxygen consumption rate; OXPHOS: oxidative phosphorylation; PRKA/PKA: protein kinase cAMP-activated; PTC: papillary thyroid carcinoma; SREBF1/SREBP1: sterol regulatory element binding transcription factor 1.

Observation of naturally canalized phonon polaritons in LiV2O5 thin layers.

Polariton canalization is characterized by intrinsic collimation of energy flow along a single crystalline axis. This optical phenomenon has been experimentally demonstrated at the nanoscale by stacking and twisting van der Waals (vdW) layers of α-MoO3, by combining α-MoO3 and graphene, or by fabricating an h-BN metasurface. However, these material platforms have significant drawbacks, such as complex fabrication and high optical losses in the case of metasurfaces. Ideally, it would be possible to canalize polaritons "naturally" in a single pristine layer. Here, we theoretically predict and experimentally demonstrate naturally canalized phonon polaritons (PhPs) in a single thin layer of the vdW crystal LiV2O5. In addition to canalization, PhPs in LiV2O5 exhibit strong field confinement ( λ p ~ λ 0 27 ), slow group velocity (0.0015c), and ultra-low losses (lifetimes of 2 ps). Our findings are promising for the implementation of low-loss optical nanodevices where strongly directional light propagation is needed, such as waveguides or optical routers.

Patterns of genetic divergence in the Rio Grande cooter (Pseudemys gorzugi), a riverine turtle inhabiting an arid and anthropogenically modified system.

The lower Rio Grande and Pecos River of the southwest United States of America have been heavily modified by human activities, profoundly impacting the integrity of their aquatic wildlife. In this context, we focused our study on the population genomics of the Rio Grande Cooter (Pseudemys gorzugi), a freshwater turtle of increasing conservation concern, residing in these two rivers and their tributaries. The genetic data revealed two distinct populations: one in the Pecos and Black rivers of New Mexico, and another in the Rio Grande and Devils River of Texas, with admixed individuals identified at the confluence of the Rio Grande and Pecos River. In addition to having a smaller geographic range, we found lower observed heterozygosity, reduced nucleotide diversity, and a smaller effective population size (Ne) in New Mexico population. Our results depict a significant isolation-by-distance pattern across their distribution, with migration being notably infrequent at river confluences. These findings are pivotal for future conservation and restoration strategies, emphasizing the need to recognize the unique needs of each population.

Lateral-type posterior fossa ependymomas in pediatric patients: a national collaborative study.

PURPOSE: To review a multicentric series of lateral-type posterior fossa ependymomas operated in the last ten years and to analyze the factors related to clinical evolution and tumor survival. METHODS: Descriptive, retrospective study. Active members of the Spanish Society of Pediatric Neurosurgery were invited to participate in this multicentric study. Clinical and radiological data were incorporated to an open database. The role of histologic grade, grade of resection, postoperative morbidities, and clinical follow-up was evaluated through bivariate associations (chi-square), Kaplan-Meier's curves (log-rank test), and multivariate analysis (binary logistic regression). RESULTS: Fourteen centers entered the study, and 25 cases with a minimum follow-up of 6 months were included. There were 13 boys and 12 girls with a mean age close to 3 years. Mean tumor volume at diagnosis was over 60 cc. A complete resection was achieved in 8 patients and a near-total resection in 5 cases. Fifteen tumors were diagnosed as ependymoma grade 2 and ten as ependymoma grade 3. Major morbidity occurred postoperatively in 14 patients but was resolved in twelve within 6 months. There were six cases of death and 11 cases of tumor progression along the observation period. Mean follow-up was 44.8 months. Major morbidity was significantly associated with histologic grade but not with the degree of resection. Overall and progression-free survival were significantly associated with complete surgical resection. At the last follow-up, 16 patients carried a normal life, and three displayed a mild restriction according to Lansky's scale. CONCLUSIONS: Lateral-type posterior fossa ependymomas constitute a specific pathologic and clinical tumor subtype with bad prognosis. Gross total resection is the goal of surgical treatment, for it significantly improves prognosis with no additional morbidity. Neurological deficits associated to lower cranial nerve dysfunction are common, but most are transient. Deeper genetic characterization of these tumors may identify risk factors that guide new treatments and stratification of adjuvant therapies.

Epidemiology of human papillomavirus-associated anogenital cancers in Granada: a three-decade population-based study.

Introduction: HPV infection is a common risk factor for all anogenital cancers. However, there are important differences in the epidemiology of anogenital cancers and these have not been compared considering diverse epidemiological indicators over a long period of time. To fill this gap, we investigated incidence, mortality, and survival trends of anogenital cancers over a period of three decades. Methods: We conducted an observational registry-based study using data from the population-based cancer registry of Granada in southern Spain. We collected data on all incident cases of anogenital cancer (cervical, anal, penile, vulvar, and vaginal cancer) diagnosed between 1985 and 2017. We calculated crude and age-standardized incidence and mortality rates, and 1, 3, and 5-year overall and net survival. We further conducted time-trend analysis calculating annual percent changes (APC) for each cancer site. Results: The incidence of anogenital cancers decreased slightly during the past 30 years, with the exception of vulvar cancer, where a slight increase was observed. Mortality decreased significantly for cervical cancer over the study period but increased non-significantly for the remaining cancer sites. Survival rates were similar to those reported in comparable countries and increased for cervical and vulvar cancer. Discussion: Cervical cancer was the greatest contributor to the burden of anogenital cancers and showed a marked improvement in all indicators in comparison to the remaining cancer sites.

Terahertz Twistoptics-Engineering Canalized Phonon Polaritons.

The terahertz (THz) frequency range is key to studying collective excitations in many crystals and organic molecules. However, due to the large wavelength of THz radiation, the local probing of these excitations in smaller crystalline structures or few-molecule arrangements requires sophisticated methods to confine THz light down to the nanometer length scale, as well as to manipulate such a confined radiation. For this purpose, in recent years, taking advantage of hyperbolic phonon polaritons (HPhPs) in highly anisotropic van der Waals (vdW) materials has emerged as a promising approach, offering a multitude of manipulation options, such as control over the wavefront shape and propagation direction. Here, we demonstrate the THz application of twist-angle-induced HPhP manipulation, designing the propagation of confined THz radiation between 8.39 and 8.98 THz in the vdW material α-molybdenum trioxide (α-MoO3), hence extending twistoptics to this intriguing frequency range. Our images, recorded by near-field optical microscopy, show the frequency- and twist-angle-dependent changes between hyperbolic and elliptic polariton propagation, revealing a polaritonic transition at THz frequencies. As a result, we are able to allocate canalization (highly collimated propagation) of confined THz radiation by carefully adjusting these two parameters, i.e. frequency and twist angle. Specifically, we report polariton canalization in α-MoO3 at 8.67 THz for a twist angle of 50°. Our results demonstrate the precise control and manipulation of confined collective excitations at THz frequencies, particularly offering possibilities for nanophotonic applications.

Fetal heart rate changes and labor neuraxial analgesia: a machine learning approach.

BACKGROUND: Neuraxial labor analgesia has been associated with fetal heart rate changes. Fetal bradycardia is multifactorial, and predicting it poses a significant challenge to clinicians. Machine learning algorithms may assist the clinician to predict fetal bradycardia and identify predictors associated with its presentation. METHODS: A retrospective analysis of 1077 healthy laboring parturients receiving neuraxial analgesia was conducted. We compared a principal components regression model with tree-based random forest, ridge regression, multiple regression, a general additive model, and elastic net in terms of prediction accuracy and interpretability for inference purposes. RESULTS: Multiple regression identified combined spinal-epidural (CSE) (p = 0.02), interaction between CSE and dose of phenylephrine (p < 0.0001), decelerations (p < 0.001), and the total dose of bupivacaine (p = 0.03) as associated with decrease in fetal heart rate. Random forest exhibited good predictive accuracy (mean standard error of 0.92). CONCLUSION: Use of CSE, presence of decelerations, total dose of bupivacaine, and total dose of vasopressors after CSE are associated with decreases in fetal heart rate in healthy parturients during labor. Prediction of changes in fetal heart rate can be approached with a tree-based random forest model with good accuracy with important variables that are key for the prediction, such as CSE, BMI, duration of stage 1 of labor, and dose of bupivacaine.

Prognostic value of metabolic parameters measured by first responders attending patients with severe trauma: associations with the New Injury Severity Score and mortality. / Valor pronóstico de los parámetros metabólicos medidos en la asistencia inicial a pacientes con trauma grave: asociación con la puntuación de la escala NISS y la mortalidad.

OBJECTIVES: Patients with severe or potentially severe trauma must be identified early, a challenge in prehospital settings. This study aimed to analyze the possible diagnostic and prognostic usefulness of analytical markers recorded in the early moments of care. MATERIAL AND METHODS: Observational study of information extracted from the prospective multicenter Code Trauma database for 2016-2019, excluding data for isolated head injuries. Using the New Injury Severity Score (NISS), we classified cases into 4 levels of severity. NISS and mortality were considered the dependent variables in inferential analyses. We calculated the areas under receiver operating characteristic curves, identified optimal cutoff points (Youden index), and calculated positive (PPV) and negative predictive values.. RESULTS: Of the 1039 trauma patients in the registry, 709 were included in the study. Their mean (SD) age was 40.4 (17.3) years, and 77.3% were men. Motorcycle accidents were the most common causes of trauma (in 21%), and mortality was 12.1%. Lactate concentration, pH, PCO2, hemoglobin concentration, hematocrit, and blood sugar were significantly associated with severity and mortality. The PPVs corresponding to pH for the 4 NISS score groups (34-41, 42-49, 50-59, and $ 60) and mortality, respectively, were 61.2, 64.1, 70.7, 62.2, and 66.6. The PPVs of traditionally used clinical variables were lower. CONCLUSION: Patients with more severe trauma had lower pH values and higher PCO2, lactate, and base excess values. PCO2, pH, and blood sugar findings were the best predictors of severity. Metabolic variables are better predictors than traditionally recorded hemodynamic variables.

OBJETIVO: En entornos de emergencia prehospitalarios, la detección temprana de un paciente con trauma grave o potencialmente crítico es un desafío. El objetivo es analizar las posibilidades diagnósticas y pronóstico de los parámetros analíticos obtenidos en los primeros momentos de la asistencia inicial. METODO: Estudio observacional multicéntrico de la base de datos prospectiva "Código Trauma" de 2016-2019 excluyendo el trauma craneoencefálico aislado. La evaluación de las lesiones se realizó utilizando el New Injury Severity Score (NISS). Los pacientes fueron clasificados en 4 grupos según nivel de gravedad. Para el análisis inferencial, las puntuaciones NISS y el resultado de mortalidad se consideraron variables dependientes. Se realizó el análisis de la curva ROC, puntos de corte óptimos mediante el índice de Youden y se calcularon los valores predictivos positivo (VPP) y negativo. RESULTADOS: De los 1.039 pacientes traumatizados del registro, 709 fueron incluidos en el estudio, con una edad media de 40,4 años (DE 17,3), 77,3% eran varones, el mecanismo lesional principal accidentes de moto (21%) y la mortalidad del 12,1%. El pH, lactato, pCO2, hemoglobina, hematocrito y glucemia influyeron significativamente en gravedad y mortalidad. El VPP de mortalidad para pH fue 61,2, 64,1, 70,7, 62,2 y 66,6 para los grupos de NISS 34- 41, 42-49, 50-59 y $ 60 puntos la mortalidad, respectivamente. Las variables clínicas clásicas obtuvieron valores más bajos. CONCLUSIONES: Los pacientes con mayor gravedad presentaron menor pH y concentraciones más altas de pCO2, lactato y exceso de bases. El pH, la pCO2 y la glucemia tuvieron la mayor capacidad predictiva de gravedad. La capacidad predictiva de los valores metabólicos es superior a la de los valores hemodinámicos clásicos.

Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway.

The propagation and diversification of signals downstream of the T cell receptor (TCR) involve several adaptor proteins that control the assembly of multimolecular signaling complexes (signalosomes). The global characterization of changes in protein-protein interactions (PPI) following genetic perturbations is critical to understand the resulting phenotypes. Here, by combining genome editing techniques in T cells and interactomics studies based on affinity purification coupled to mass spectrometry (AP-MS) analysis, we determined and quantified the molecular reorganization of the SLP76 interactome resulting from the ablation of each of the three GRB2-family adaptors. Our data showed that the absence of GADS or GRB2 induces a major remodeling of the PPI network associated with SLP76 following TCR engagement. Unexpectedly, this PPI network rewiring minimally affects proximal molecular events of the TCR signaling pathway. Nevertheless, during prolonged TCR stimulation, GRB2- and GADS-deficient cells displayed a reduced level of activation and cytokine secretion capacity. Using the canonical SLP76 signalosome, this analysis highlights the plasticity of PPI networks and their reorganization following specific genetic perturbations.

Valor pronóstico de los parámetros metabólicos medidos en la asistencia inicial a pacientes con trauma grave: asociación con la puntuación de la escala NISS y la mortalidad / Prognostic value of metabolic parameters measured by first responders attending patients with severe trauma: associations with the New Injury Severity Score and mortality

Objetivos. En entornos de emergencia prehospitalarios, la detección temprana de un paciente con trauma grave o potencialmente crítico es un desafío. El objetivo es analizar las posibilidades diagnósticas y pronóstico de los parámetros analíticos obtenidos en los primeros momentos de la asistencia inicial. Métodos. Estudio observacional multicéntrico de la base de datos prospectiva “Código Trauma” de 2016-2019 excluyendo el trauma craneoencefálico aislado. La evaluación de las lesiones se realizó utilizando el New Injury Severity Score (NISS). Los pacientes fueron clasificados en 4 grupos según nivel de gravedad. Para el análisis inferencial, las puntuaciones NISS y el resultado de mortalidad se consideraron variables dependientes. Se realizó el análisis de la curva ROC, puntos de corte óptimos mediante el índice de Youden y se calcularon los valores predictivos positivo (VPP) y negativo. Resultados. De los 1.039 pacientes traumatizados del registro, 709 fueron incluidos en el estudio, con una edad media de 40,4 años (DE 17,3), 77,3% eran varones, el mecanismo lesional principal accidentes de moto (21%) y la mortalidad del 12,1%. El pH, lactato, pCO2, hemoglobina, hematocrito y glucemia influyeron significativamente en gravedad y mortalidad. El VPP de mortalidad para pH fue 61,2, 64,1, 70,7, 62,2 y 66,6 para los grupos de NISS 34-41, 42-49, 50-59 y $ 60 puntos la mortalidad, respectivamente. Las variables clínicas clásicas obtuvieron valores más bajos. Conclusiones. Los pacientes con mayor gravedad presentaron menor pH y concentraciones más altas de pCO2, lactato y exceso de bases. El pH, la pCO2 y la glucemia tuvieron la mayor capacidad predictiva de gravedad. La capacidad predictiva de los valores metabólicos es superior a la de los valores hemodinámicos clásicos. (AU)

Background and objective: Patients with severe or potentially severe trauma must be identified early, a challenge in prehospital settings. This study aimed to analyze the possible diagnostic and prognostic usefulness of analytical markers recorded in the early moments of care. Methods: Observational study of information extracted from the prospective multicenter Code Trauma database for 2016-2019, excluding data for isolated head injuries. Using the New Injury Severity Score (NISS), we classified cases into 4 levels of severity. NISS and mortality were considered the dependent variables in inferential analyses. We calculated the areas under receiver operating characteristic curves, identified optimal cutoff points (Youden index), and calculated positive (PPV) and negative predictive values. Results: Of the 1039 trauma patients in the registry, 709 were included in the study. Their mean (SD) age was 40.4 (17.3) years, and 77.3% were men. Motorcycle accidents were the most common causes of trauma (in 21%), and mortality was 12.1%. Lactate concentration, pH, PCO2, hemoglobin concentration, hematocrit, and blood sugar were significantly associated with severity and mortality. The PPVs corresponding to pH for the 4 NISS score groups (34-41, 42-49, 50-59, and $ 60) and mortality, respectively, were 61.2, 64.1, 70.7, 62.2, and 66.6. The PPVs of traditionally used clinical variables were lower. Conclusions: Patients with more severe trauma had lower pH values and higher PCO2, lactate, and base excess values. PCO2, pH, and blood sugar findings were the best predictors of severity. Metabolic variables are better predictors than traditionally recorded hemodynamic variables. (AU)

Development and psychometric properties of a measurement to ascertain the impact of genitourinary symptoms on health-related quality of life in menopausal women: the Cervantes-GSM questionnaire.

OBJECTIVE: The Cervantes-GSM questionnaire is a novel tool currently being developed to examine the impact of genitourinary symptoms on health-related quality of life in adult women with genitourinary syndrome of menopause (GSM). METHODS: A literature review and cognitive debriefing were conducted in women with GSM, which provided the basis for creating a draft questionnaire. This draft version was pilot-tested to check participant comprehension and ease of completion. The initial draft was then refined to obtain a 15-item version with five domains whose initial psychometric properties were analyzed in 130 adult women with GSM. The psychometric properties tested in this study were factorial structure, feasibility, reliability, and construct validity. RESULTS: The Cervantes-GSM 15-item questionnaire consists of five domains: vulvovaginal symptoms, urinary symptoms, psychological (emotions), interference with daily activities, and sexuality. The instrument was shown to be feasible and easy to complete, regardless of age or educational level. Internal consistency was high (Cronbach α = 0.88). Construct validity was supported by convergent-divergent validity showing higher correlation coefficients between items in their own domain (>0.70) than with the other items and domains in the questionnaire. Cervantes-GSM also showed known group validity with significant differences in total score and most domains (13-20 points, P < 0.01) regardless of whether women chose local treatment of their genitourinary symptoms. CONCLUSION: This study presents a novel questionnaire capable of assessing health-related quality of life in menopausal women with GSM. The tool has shown acceptable preliminary psychometric properties, including feasibility, factor structure, construct validity, and internal consistency.

Disease burden and costs for patients with hip and knee osteoarthritis and chronic moderate-to-severe refractory pain on treatment with strong opioids in Spain.

INTRODUCTION AND OBJECTIVES: To determine the disease burden and costs in patients with hip or knee OA and chronic moderate-to-severe refractory pain, receiving strong opioids in Spain. MATERIALS AND METHODS: This was a 36-month longitudinal secondary analysis of the real-word OPIOIDS study. Patients aged ≥18 years with hip or knee OA and chronic moderate-to-severe refractory pain receiving strong opioids were considered. The disease burden included analgesia assessments (NRS scale), cognitive functioning (MMSE scale), basic activities of daily living (Barthel index), and comorbidities (severity and frequency). Costs due to the use of healthcare resources and productivity loss were estimated. RESULTS: 2832 patients were analyzed; age was 72.0 years (SD=14.3), 76.8% were women. Patients had mainly been treated with fentanyl (n=979; 37.6%), tapentadol (n=625; 24.0%), oxycodone (n=572; 22.0%), and buprenorphine (n=425; 16.3%). Pain intensity decreased by 1 point (13.7%), with a 2.6-point decline in the cognitive scale (14.3%, with a 5.3%-increase in patients with cognitive deficit) over a mean treatment period of 384.6 days (SD: 378.8). Barthel scores decreased significantly yielding to a slightly increase in proportion of patients with severe-to-total dependency; 1.2%-2.9%. In the first year of treatment, average healthcare costs were €2013/patient, whereas the average productivity loss cost was €12,227/working-active patient. DISCUSSION AND CONCLUSIONS: Strong opioids resulted in high healthcare costs with a limited reduction in pain, an increase in cognitive deficit, and a slight increase of patients with severe to total dependency over 36 months of treatment.

Spinal Cord Stimulation for the Treatment of Refractory Pain From Tarlov Cysts: A Case Report.

Tarlov cysts are extradural meningeal cysts with a collection of cerebrospinal fluid that most often affects sacral nerve roots, causing chronic low back pain and radiculopathy. Still, there is no consensus regarding the best treatment for symptomatic cysts. We describe a patient who developed worsening lower back pain and radiculopathy after interventional drainage and surgical management. Medication and various procedures failed to relieve the pain. Subsequently, the patient received significant pain relief from spinal cord stimulation (SCS). This case provides evidence that SCS could be used to manage refractory pain from Tarlov cysts that have failed to respond to other treatment modalities.

Disease burden and costs for patients with hip and knee osteoarthritis and chronic moderate-to-severe refractory pain on treatment with strong opioids in Spain / Carga de la enfermedad y costes en pacientes con osteoartritis de cadera y rodilla con dolor crónico refractario moderado-severo tratados con opioides mayores en España

Introduction and objectives: To determine the disease burden and costs in patients with hip or knee OA and chronic moderate-to-severe refractory pain, receiving strong opioids in Spain. Materials and methods: This was a 36-month longitudinal secondary analysis of the real-word OPIOIDS study. Patients aged ≥18 years with hip or knee OA and chronic moderate-to-severe refractory pain receiving strong opioids were considered. The disease burden included analgesia assessments (NRS scale), cognitive functioning (MMSE scale), basic activities of daily living (Barthel index), and comorbidities (severity and frequency). Costs due to the use of healthcare resources and productivity loss were estimated. Results: 2832 patients were analyzed; age was 72.0 years (SD=14.3), 76.8% were women. Patients had mainly been treated with fentanyl (n=979; 37.6%), tapentadol (n=625; 24.0%), oxycodone (n=572; 22.0%), and buprenorphine (n=425; 16.3%). Pain intensity decreased by 1 point (13.7%), with a 2.6-point decline in the cognitive scale (14.3%, with a 5.3%-increase in patients with cognitive deficit) over a mean treatment period of 384.6 days (SD: 378.8). Barthel scores decreased significantly yielding to a slightly increase in proportion of patients with severe-to-total dependency; 1.2%–2.9%. In the first year of treatment, average healthcare costs were €2013/patient, whereas the average productivity loss cost was €12,227/working-active patient. Discussion and conclusions: Strong opioids resulted in high healthcare costs with a limited reduction in pain, an increase in cognitive deficit, and a slight increase of patients with severe to total dependency over 36 months of treatment.(AU)

Introducción y objetivos: Determinar la carga de la enfermedad y los costes en pacientes con osteoartritis de cadera y rodilla y dolor crónico refractario moderado-severo, en tratamiento con opioides mayores en España. Materiales y métodos: Se trata de un subanálisis de 36 meses de duración, procedente del estudio observacional OPIOIDS. Participaron pacientes con una edad ≥18 años, diagnosticados con osteoartritis de cadera y rodilla y dolor crónico refractario moderado-severo, en tratamiento con opioides mayores. La carga de la enfermedad incluyó la evaluación de la analgesia (escala NRS), del funcionamiento cognitivo (escala MMSE), de la capacidad para realizar las actividades de la vida diaria (índice de Barthel) y de las comorbilidades (gravedad y frecuencia). También se estimaron los costes asociados al uso de recursos sanitarios y a la productividad laboral. Resultados: Se analizaron 2.832 pacientes (edad: 72,0 años [DE: 14,3]; mujeres: 76,8%), que habían sido principalmente tratados con fentanilo (n=979; 37,6%), tapentadol (n=625; 24,0%), oxicodona (n=572; 22,0%) y buprenorfina (n=425; 16,3%). La intensidad del dolor disminuyó una unidad (13,7%), con una reducción de 2,6 unidades en la escala cognitiva (14,3% y aumento del 5,3% en los pacientes con déficit cognitivo) durante una media de 384,6 días (DE: 378,8). Las puntuaciones en la escala de Barthel disminuyeron significativamente, con un ligero aumento en la proporción de pacientes con dependencia grave/total, entre 1,2% y 2,9%. En el primer año, los costes sanitarios medios fueron 2.013€/paciente, mientras que los costes medios de pérdida de productividad fueron 12.227€/trabajador. Discusión y conclusiones: El tratamiento con opioides mayores durante 36 meses implicó elevados costes sanitarios, con una eficacia analgésica limitada, un aumento del déficit cognitivo y un ligero aumento de los pacientes con dependencia grave/total.(AU)

Sensitivity-to-change and predictive validity of the Cervantes Short-Form (C-SF) questionnaire in postmenopausal women.

OBJECTIVES: To explore, for the first time, the ability of the Cervantes Short-Form (C-SF) questionnaire to detect and to predict meaningful changes (sensitivity-to-change and predictive validity) in women with menopausal symptoms receiving any therapeutic management under routine medical care. METHODS: Postmenopausal women included in a registry study were the source of data. Sensitivity-to-change was explored by assessing the responses of C-SF to different type of treatment management: no treatment, natural therapies or systemic hormonal therapy (SHT). Predictive validity assessed the ability of baseline score to predict the reduction in the impact of menopausal symptoms in C-SF scoring equal or higher than one time its minimally important difference (MID) of improvement (response rate). RESULTS: A total of 245 women were enrolled. C-SF score was significantly reduced (better QoL) with SHT by 10.62 points versus no change or 2.32 point by natural therapies or no treatment, respectively (p < 0.001 in both cases). Women declaring better improvement after treatment showed higher significant reduction in C-SF score versus those with no self-perceived improvement or impairment: -12.49 point versus +1.06 and +12.71, respectively (p < 0,01 in both cases). Responder rate showed a significant lineal growing trend with higher C-SF scoring at baseline in women who received SHT: higher scoring showed higher response rates (lineal Chi2 = 15.9, p < 0.001), but not in the case of receiving natural therapies or no treatment. CONCLUSIONS: C-SF was shown to be sensitive-to-change when postmenopausal QOL status changes due to mainly systemic hormonal treatment, therefore, supporting the utilization of this instrument to monitor response to treatment. Likewise, pre-treatment scoring in C-SF was able to predict woman's QOL meaningful response with hormonal treatment.

Gender Gap: A Qualitative Study of Women and Leadership Acquisition in Anesthesiology.

BACKGROUND: The representation of women among leaders in the field of anesthesia continues to trail that of their male counterparts. This qualitative study was conducted to understand the pathway of leadership acquisition among women in the field of anesthesiology. METHODS: Using constructivist grounded theory, we sought to determine whether there were specific internal or external factors that were common to women in leadership in the specialty field of anesthesiology, and specifically, how they obtained leadership positions. Semistructured interviews were conducted for data collection. A total of 26 women in leadership positions in anesthesiology participated in this study. RESULTS: The analysis of these interviews resulted in the development of 4 common themes related to career pathways for these women in leadership. Each theme was examined in depth to determine the qualities necessary for individuals to advance in the field and the pathway to obtaining leadership positions. The findings of this study showed that early-career, high-value mentorship and sponsorship were important factors in leadership acquisition. Most participants (n = 20; 76%) had early mentors. Of those with early mentorship, 13 (65%) had high-value mentors, who we define as someone with power or authority. Sponsorship was the leading factor contributing to leadership acquisition. CONCLUSIONS: The results of this qualitative study may serve as a guide for encouraging female anesthesiologists with leadership aspirations. We suggest that the specialty field of anesthesiology institute targeted measures to help increase the percentage of women leadership with formal sponsorship programs at the local and national levels.