Targeting the orexin/hypocretin system for the treatment of neuropsychiatric and neurodegenerative diseases: From animal to clinical studies.

Orexins (also known as hypocretins) are neuropeptides located exclusively in hypothalamic neurons that have extensive projections throughout the central nervous system and bind two different G protein-coupled receptors (OX1R and OX2R). Since its discovery in 1998, the orexin system has gained the interest of the scientific community as a potential therapeutic target for the treatment of different pathological conditions. Considering previous basic science research, a dual orexin receptor antagonist, suvorexant, was the first orexin agent to be approved by the US Food and Drug Administration to treat insomnia. In this review, we discuss and update the main preclinical and human studies involving the orexin system with several psychiatric and neurodegenerative diseases. This system constitutes a nice example of how basic scientific research driven by curiosity can be the best route to the generation of new and powerful pharmacological treatments.

Electroporation saves the day again: Pulsed-field ablation for phrenic nerve-sparing in right atrial tachycardia.

INTRODUCTION: Pulsed-field ablation (PFA) is a novel nonthermal energy that shows unique features that can be of use beyond pulmonary vein ablation, like tissue selectivity or proximity rather than contact dependency. METHODS AND RESULTS: We report three cases of right focal atrial tachycardias arising from the superior cavoatrial junction and the crista terminalis, in close relationship with the phrenic nerve, effectively ablated using a commercially available PFA catheter designed for pulmonary vein isolation without collateral damage. CONCLUSION: PFA can be useful for treating right atrial tachycardias involving sites near the phrenic nerve, avoiding the need for complex nerve-sparing strategies.

Healthcare service use for children with chronic complex diseases: A longitudinal six-year follow-up study.

PURPOSE: The objective was analysed the patterns use of healthcare services of this population and the influence of their clinical and sociodemographic characteristics. DESIGN AND METHODS: A six-year longitudinal follow-up study was performed to evaluate the annual healthcare resources use and clinical data among children with complex chronic diseases in Spain between 2015 and 2021. The sample trends in healthcare usage and the associated factors were analysed using ANCOVA and multivariable linear regression models. RESULTS: Patients had high attendance during the follow-up period, with >15 episodes year. This trend decreased over time, especially in children with oncological diseases compared with other diseases (F (16.75; 825.4) = 32.457; p < 0.001). A multivariable model showed that children with a greater number of comorbidities (ß = 0.17), shorter survival time (ß = -0.23), who had contact with the palliative care unit (ß = 0.16), and whose mothers had a higher professional occupation (ß = 0.14), had a greater use of the healthcare system. CONCLUSIONS: Children with a higher number of comorbidities and the use of medical devices made a greater frequentation of health services, showing a trend of decreasing use over time. Socioeconomic factors such as mothers' occupational status determine healthcare frequentation. These results suggest the existence of persistent gaps in care coordination sustained over time. PRACTICAL IMPLICATIONS: Systematized and coordinated models of care for this population should consider the presence of inequalities in health care use.

A new score for life-threatening ventricular arrhythmias and sudden cardiac death in adults with transposition of the great arteries and a systemic right ventricle.

AIMS: To investigate the incidence of major adverse ventricular arrhythmias and related events (MAREs) and to develop a stratification tool predicting MAREs in adults with a systemic right ventricle (sRV). METHODS AND RESULTS: In a multicentre approach, all adults (≥16 years old) with a sRV undergoing follow-up between 2000 and 2018 were identified. The incidence of MAREs, defined as sudden cardiac death, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator (ICD) therapy, was analysed. The association of MAREs with clinical, electrical, and echocardiographic parameters was evaluated. A total of 1184 patients (median age 27.1 years; interquartile range 19.9-34.9 years; 59% male; 70% with atrial switch repair for D-transposition of the great arteries) were included. The incidence of MAREs was 6.3 per 1000 patient-years. On multivariate analysis, age, history of heart failure, syncope, QRS duration, severe sRV dysfunction and at least moderate left ventricular outflow tract obstruction were retained in the final model with a C-index of 0.78 [95% confidence interval (CI) 0.72-0.83] and a calibration slope of 0.93 (95% CI 0.64-1.21). For every five ICDs implanted in patients with a 5-year MARE risk >10%, one patient may potentially be spared from a MARE. CONCLUSION: Sudden cardiac death remains a devastating cause of death in a contemporary adult cohort with a sRV. A prediction model based on clinical, electrocardiographic, and echocardiographic parameters was devised to estimate MARE risk and to identify high-risk patients who may benefit from primary prevention ICD implantation.

Characterization of high-power and very-high-power short-duration radiofrequency lesions performed with a new-generation catheter and a temperature-control ablation mode.

INTRODUCTION: High-power short-duration (HPSD) has been proposed to shorten procedure times while maintaining efficacy and safety. We evaluated the differences in size and geometry between radiofrequency lesions obtained with this method and conventional ones. METHODS AND RESULTS: Twenty-eight sets of 10 perpendicular radiofrequency applications were performed with two commercially available catheters: a temperature-controlled HPSD catheter (QDot-Micro) and a conventional power-controlled catheter (Thermocool SmartTouch) on porcine left ventricle. Different power settings (35, 40, 50, and 90 W), contact force (CF; 10 and 20 g), ablation index (AI; 400 and 550), and application times were combined to create conventional (35-40 W), HPSD (50 W) and very-high-power short-duration (VHPSD; 90 W) lesions, that were cross-sectioned and measured. About 4-s VHPSD lesions were smaller, shallower, and thinner than HPSD performed with the QDot-Micro catheter in any scenario of CF or AI (61 ± 7.8 mm3 , 6.1 ± 0.3 mm wide, and 2.9 ± 0.1 mm deep with 10 g; 72.2 ± 0.5 mm3 , 6.8 ± 0.3 mm wide, and 2.9 ± 0.2 mm deep with 20 g). Conventional and HPSD lesions performed with the temperature-controlled catheter were generally bigger, deeper, and wider than the ones obtained with the power-controlled catheter, as well as more consistent in size. This was especially true with the lower CF and AI scenario, while differences were less notable with other setting combinations. CONCLUSION: VHPSD lesions performed with QDot-Micro catheter were smaller than any other lesions, which is especially attractive for posterior left atrial wall ablation. On the contrary, conventional-powered and HPSD lesions performed with this catheter were equally sized (or even bigger with lower CF and AI objectives), as well as more consistent in size, which would guarantee transmurality in other locations.

Increasing Incidence of mucormycosis in Spanish inpatients from 1997 to 2018.

BACKGROUND: Mucormycosis is a worldwide angio-invasive fungal infection that is associated with high morbidity and mortality. A few European studies have focused on the epidemiology. METHODOLOGY: A retrospective longitudinal descriptive study was performed with inpatients diagnosed with mucormycosis (ICD-9-CM, code 117.7, cases 1997-2015; and ICD-10, code B46, cases 2016-2018; along with length of hospital stay) in Spanish public hospitals between 1 January 1997 and 31 December 2018. Data were obtained from the Minimum Basic Data Set (CMBD in Spanish). PRINCIPAL FINDINGS: A total of 962 patients were recorded; 665 were men. The mean age (±SD) was 55 ± 18.8 years. The annual incidence rate increased from 0.74 to 1.24 cases per million person-years. The lethality rate was 31.3%. Renal failure (41.6%) and haematological malignancy (36.3%) were the main factors involved. CONCLUSIONS: Mucormycosis is a rare infectious disease in Spain, but it has had a significantly increased incidence in the last two decades. Being an adult male and having diabetes, neoplasm or renal failure are the main factors associated. High mortality is usually associated mainly with haematological malignancy and renal failure. CMBD studies could be an efficient tool for assessing changes in the epidemiology of mucormycosis.

An Approach to Minimize Tumour Proliferation by Reducing the Formation of Components for Cell Membrane.

Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated ß-cyclodextrin Sodium Salt (SBE-ß-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 µM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer.

A protocol for a randomized trial measuring flowmetry in risk areas for pressure ulcer: Hyperoxygenated fatty acids vs olive oil.

BACKGROUND: Pressure ulcers are a common adverse event in healthcare. To date, no flowmetry studies have been conducted to compare hyperoxygenated fatty acids (HFA) vs. extra-virgin olive oil (EVOO) in alleviating this condition. AIMS: To determine and evaluate the effect of the application of HFA vs. EVOO on tissue oxygenation and perfusion in heels under pressure, in healthy persons and in hospitalised patients. DESIGN: Two-phase experimental study. METHODS: Phase 1 will be conducted with healthy subjects, using a randomised, open study design, evaluating an intrasubject control group. Phase 2 will focus on hospitalised subjects, with a randomised, open study group vs. a control group. DISCUSSION: This Project is undertaken to identify the mechanisms that intervene in the genesis of pressure ulcers and to determine whether there are differences in outcomes between the application of HFA vs. EVOO as a preventive measure The results of this study are of economic importance (due to the price difference between the products used) and will also impact on usual clinical practice for patients with impaired mobility and liable to suffer from pressure ulcers, by considering an alternative to established preventive measures.

Epidemiology of aspergillosis in hospitalised Spanish patients-A 21-year retrospective study.

BACKGROUND: Aspergillosis is a serious infection, and in Spain, the influence of epidemiology and climate on the resulting expenses of aspergillosis is not well established. AIM: A retrospective descriptive study using the Minimum Basic Data Set was performed on records of patients admitted to hospitals of the National Health System between 1997 and 2017 with a diagnosis of aspergillosis. The weather parameters were obtained from the State Agency of Meteorology from Spain. RESULTS: A total of 32,960 patients were identified, of whom 22,383 were men (68%). The mean age (±SD) was 61.1 ± 19.1 years. The mean incidence rate for all diagnoses was 3.54 cases per 100,000 person-years (95% CI, 3.50-3.57). The incidence rate in men was twice as high as that in women, 4.89 (95% CI, 4.82-4.95) vs. 2.24 (95% CI, 2.19-2.27) cases per 100,000 person-years (p > .001). The highest incidence rates were concentrated in northern Spain. One in four patients died (8,080 cases; 25%). There was a moderate positive linear association between rainfall and incidence rate (rP  = .508; p = .026). In contrast, the Pearson's correlation coefficient indicated a moderate negative linear relationship between temperature and incidence rate (rP  = -.447; p = .050). We observed a higher incidence in the months with higher humidity and rainfall. CONCLUSIONS: Our study supports a high burden of aspergillosis in Spain, with an increase in cases in the past two decades. Additionally, the influence of climatological factors on the incidence of aspergillosis is highlighted. Despite preemptive treatment strategies, this infection still has a high mortality.

Propranolol syrup to tablets change triggers electrical storm in Jervell-Lange-Nielsen syndrome.

A 10-year-old girl with genetically confirmed Jervell-Lange-Nielsen syndrome treated with beta-blocker and developed electrical storm after changing propranolol syrup to tablets. Jervell-Lange-Nielsen is characterised by long QT and congenital sensorineural deafness, with high risk of malignant arrhythmias at early ages. Gastric involvement and achlorhydria may be present, with subsequent alteration of medication bioavailability which can trigger severe arrhythmic complications.

Effectiveness of a Diabetes Education Program based on Tailored interventions and Theory of Planned Behaviour: Cluster randomized controlled trial protocol.

AIM: To measure the Effectiveness of a Diabetes Education Program for people with T2DM, based on Tailored interventions and the Theory of Planned Behaviour. DESIGN: Cluster randomized controlled clinical trial. METHODS: This multicentre study will be carried out at 30 primary healthcare centres, where 436 persons with Type 2 Diabetes Mellitus (T2DM), aged between 18-75 years, will be recruited. The experimental educational program to be applied is modelled using components obtained from a systematic review and prior qualitative analysis. In addition, a taxonomy of nursing practice is used to standardize the program, based on the Theory of Planned Behaviour as a conceptual model. The intervention will be carried out by community nurses, using ADAPP-Ti® , an application developed with FileMaker Pro v.18. The control group will receive usual care and data will be collected at 6, 12, and 18 months, for both groups. The primary outcome considered will be glycosylated haemoglobin and cardiovascular factors, while the secondary ones will be tobacco consumption, body mass index, barriers to self-care, health-related quality of life, and lifestyle modification. The protocol was approved by the Ethics Committee of the Province of Malaga (Spain) in November 2014. DISCUSSION: The degree of metabolic control in T2DM is not always associated with healthy lifestyles and significant levels of medication are often prescribed to achieve clinical objectives. An intervention focused on needs, based on the best available evidence and a solid conceptual framework, might successfully consolidate appropriate self-care behaviour in this population. IMPACT: The study will result in the publication of an educational program featuring well-defined interventions and activities that will enable clinicians to tailor health care to the individual's needs and to combat treatment inertia in attending this population.

Predictors of health service use by family caregivers of persons with multimorbidity.

BACKGROUND: Informal caregivers of patients with multiple chronic conditions are socially good, promoting the sustainability of a large part of home care provision. However, this very demanding activity causes health problems that increase their own need for health services. This study analyses the use of health services by informal carers, comparing it with the use made by the general population with similar characteristics. METHODOLOGY: Cross-sectional analytical study carried out in the Malaga-Valle Guadalhorce Primary Health Care District (Spain). Healthcare demand and perceived health were measured in the family caregivers, compared to the general population. Strobe Statement for observational studies has been used to strength the report of the results. RESULTS: Final sample consisted of 314 family caregivers together with a subsample of 2.290 non-caregivers taken from data of the National Health Survey. This subsample was paired by gender with our sample. Formal caregivers make fewer annual visits to the health services, with respect to the general population, regardless of the perceived level of health. The difference of the means between those who perceive their health as very poor was 0.11 (95% CI: 0.01 to 0.20) consultations with the family doctor, 0.21 (95% CI: 0.15 to 0.26) consultations with medical specialists and 1.70 (95% CI: 1.52 to 1.87) emergency room attention. Three independent factors were identified that predispose to the increased use of health services: background of greater education achievement (OR 8.13, 95% CI: 1.30 to 50.68), non-cohabitation with the care recipient (OR 3.57, 95% CI: 1.16 to 11.11) and a more positive physical quality of life component (OR 1.06; 95% CI: 1.03 to 1.09). DISCUSSION AND IMPLICATIONS: Intrinsic components of the caregiver reveal their independent relationship with the provision of informal care and the use of health services. A broader vision is needed for the factors that influence the health of these caregivers to develop multipurpose interventions and improve the consistency and effectiveness of the health services offered to the caregiver.

New Insights in the Involvement of the Endocannabinoid System and Natural Cannabinoids in Nicotine Dependence.

Nicotine, the main psychoactive component in tobacco smoke, plays a major role in tobacco addiction, producing a high morbidity and mortality in the world. A great amount of research has been developed to elucidate the neural pathways and neurotransmitter systems involved in such a complex addictive behavior. The endocannabinoid system, which has been reported to participate in the addictive properties of most of the prototypical drugs of abuse, is also implicated in nicotine dependence. This review summarizes and updates the main behavioral and biochemical data involving the endocannabinoid system in the rewarding properties of nicotine as well as in nicotine withdrawal and relapse to nicotine-seeking behavior. Promising results from preclinical studies suggest that manipulation of the endocannabinoid system could be a potential therapeutic strategy for treating nicotine addiction.

Tissue temperature, flux and oxygen of sacral and trochanteric area under pressure of healthy subjects: A quasi-experimental study.

AIM: To evaluate the changes that take place in the perfusion, oxygenation and local temperature of the skin of the sacrum and trochanter when subjected to direct pressure for 2 h. METHODS: Quasi-experimental study in the preclinical phase with healthy subjects acting as their own controls (intrasubject control). The outcome variables were measured with a laser Doppler system (local temperature and oxygenation) and by near-infrared spectroscopy (perfusion). The pressure exerted was measured with a capacitive pressure sensor. No more than one week elapsed between the sacrum and trochanter measurements. RESULTS: The study sample consisted of 18 persons. The comparative analysis of the fluctuations in the parameters measured on the skin of the trochanters and sacrum, according to the time elapsed, revealed a statistically significant increase in temperature and in the pressure exerted. On the other hand, the changes in capillary blood flow and in SaO2 were not statistically significant. CONCLUSION: Our study results show that changes found in terms of temperature and pressure should be taking into account when planning personalised repositioning to patients according to biomechanical and biological situations that vary between anatomical areas. In future research, the changes reported could be evaluated in patients with risk factors for the development of pressure ulcers, thus facilitating the introduction of more personalised planning in the care and prevention of these injuries.

Perfusion, tissue oxygenation and peripheral temperature in the skin of heels of healthy participants exposed to pressure: a quasi-experimental study.

AIM: To evaluate the relationship between the pressure exerted on the heel of one foot resting directly on a mattress, versus that exerted on the other heel, protected by a pillow beneath the Achilles tendon area and the changes thus produced in perfusion, oxygenation and temperature in the skin of heels of healthy volunteers lying in a supine position. DESIGN: Experimental study in a pre-clinical phase, with healthy volunteer participants and intrapeople control. METHODS: The study was carried out from November 2017 - May 2018. A pressure measurement surface was placed between the participant and the constant low-pressure support surface. Doppler laser devices were used to measure local temperature and perfusion. The degree of oxygenation was determined using an infrared beam close to the pressure zone in each heel. Both feet rested immobile on the bed, in a natural position, for 2 hr. To ensure intrapeople control, in every case the left heel was raised slightly, compared with the right. RESULTS: Eighteen participants took part in this study. Analysis of the results obtained showed that capillary blood flow was significantly reduced in the heel subjected to pressure, compared with the other heel, while no significant effects on oxygen saturation or temperature were observed. The variables associated with greater oxygen saturation were capillary blood flow, local temperature and pressure exerted. Fat-free mass, fat mass and duration of exposure to pressure were all significantly associated with reduced oxygen saturation. CONCLUSIONS: In healthy participants, when the heel is subjected to constant pressure against a constant low-pressure support surface, there is a significant reduction in blood flow, compared with the heel where pressure is relieved. However, there are no significant differences in temperature or tissue oxygenation. IMPACT: Significant reductions in vascular flow were observed; however, the oxygenation and temperature of the heel tissues remained unchanged. These findings, corroborated in real patients, would advance our understanding and facilitate decision-making on measures to prevent pressure ulcers, such as repositioning or tissue protection. TRIAL REGISTRATION: The protocol is registered in ClinicalTrials.gov (NCT02736838).

Effectiveness of a hydrophobic dressing for microorganisms' colonization of vascular ulcers: Protocol for a randomized controlled trial (CUCO-UV Study).

AIM: To determine the effectiveness of a hydrophobic dressing (Cutimed Sorbact® ) against a silver dressing (Aquacel® Ag Extra) in the level of colonization of chronic venous leg ulcers. The secondary endpoints are health-related quality of life, level of pain, and time to complete healing. DESIGN: Open randomized controlled trial, with blinded endpoint. METHODS: Patients with chronic venous leg ulcers with signs of critical colonization will be randomized in a concealed sequence using computer software to receive one of the alternative dressings. A total of 204 participants recruited in Primary Health Care and nursing homes will be necessary to assure statistical power. Measures will include sociodemographic variables, wound-related variables (area, exudate, and time to healing), level of pain, adverse effects, and health-related quality of life. Smear samples will be collected from the ulcers and will be subject to DNA-typing technique through polymerase chain reaction to obtain the level of colony-forming units. Measures will be collected at baseline, 4, 8, and 12 weeks. DISCUSSION: Elevated levels of microorganisms prevent wound healing and favour its chronification. The main target when colonization is present is to reduce the bacterial load to levels that promote immune system mobilization. Hydrophobic dressings prevent the formation of biofilm in the wound by means of physical effect, so that the possibility of antimicrobial resistance is significantly reduced. IMPACT: Current evidence about the effectiveness of dressings to minimize venous leg ulcers colonization is very limited. Previous studies have important methodological flaws. This study will permit to obtain the effectiveness of hydrophobic dressings against silver dressings with a robust design based on conditions of routine clinical practice in Primary Health Care and nursing homes.

Pressure levels in the trochanter area according to repositioning at different degrees of inclination in healthy subjects.

OBJECTIVES: Patient repositioning is a recommended intervention to prevent or treat pressure ulcers (PUs). One option under consideration is the tailored repositioning according to patient characteristics, but more knowledge is needed on how different repositioning patterns influence on skin pressure. To determine what degree of inclination of the body in bed generates more pressure in the trochanteric region. Additionally, to analyze the influence of factors such as gender, age and anthropometric characteristics in the variations of this pressure. METHODS: Analytical cross-sectional study. Body Mass Index (BMI), lean mass and fat mass were measured in healthy volunteers subject to different inclinations (90°, 60° and 30°) in right lateral decubitus. Pressure was measured with a capacitive surface. RESULTS: In total, 146 subjects were included, of which 45 were men and 101 women. The results showed pressure differences due to the inclination according to gender and anthropometric values, being statistically significant in men at 90° and 60°, and in women at 30°. (hombres 90° p = 0,026, 60° p = 0,049; mujeres 30° p = 0,036) según prueba Brown-Forsythe. CONCLUSIONS: There are differences in the pressures of the trochanteric zone depending on anthropometric factors and by gender, in different body positions. Obese people exerted a higher pressure in the trochanter area at 30° of body inclination than overweight, normal weight and underweight people, respectively. From the clinical point of view, these findings invite to consider a possible differentiation in the repositioning interventions of the patients, according to gender and BMI, as a preventive strategy for PUs.

Correction to: Analyzing territory for the sustainable development of solar photovoltaic power using GIS databases.

The original version of this article unfortunately contained an error.

Development and Psychometric Validation of an Instrument to Identify Barriers to Self-Care Among Spanish Patients With Type 2 Diabetes on the Basis of Theory of Planned Behavior.

BACKGROUND: Several instruments are available to evaluate barriers to self-care in people with type 2 diabetes, but with significant psychometric weaknesses and poor theoretical background. OBJECTIVES: To develop and psychometrically validate a questionnaire to identify barriers to self-care in this population on the basis of the theory of planned behavior. METHODS: The study was carried out in 15 primary healthcare centers belonging to the Public Health Care System in Andalusia (Spain). After content validity was confirmed, an initial pilot study was undertaken (n = 54) and the model was evaluated in 2 samples of 205 subjects each to test its configural and metric invariance by confirmatory factor analysis. Internal consistency, test-retest reliability, criterion validity, and interpretability were carried out following COSMIN standards. RESULTS: A 4-factor instrument (intention, subjective norms, perceived control, and attitudes) with 15 items was obtained with a good fit: goodness-of-fit index = 0.92, comparative fit index = 0.93, and root mean square error of approximation = 0.043 (90% confidence interval 0.034-0.052). Cronbach α was 0.78, and test-retest reliability was adequate (intraclass correlation coefficient 0.73; P < .0001). The instrument revealed an adequate criterion validity depending on the treatment complexity and level of metabolic control. Thus, participants with poor self-care scores were more likely to suffer from diabetes-related complications (odds ratio 1.91; 95% confidence interval 1.15-3.1). CONCLUSIONS: A theory-driven instrument is suitable for its use with Spanish people with type 2 diabetes to assess their self-care needs and make tailored recommendations for lifestyle modifications on the basis of their behavioral determinants.

Socioeconomic Status and Health Services Utilization for Children With Complex Chronic Conditions Liable to Receive Nurse-Led Services: A Cross-Sectional Study.

AIM: To analyze the use of health services for children with severe chronic diseases, seeking to identify patterns of use according to sociodemographic and clinical conditions, and to identify unmet needs of care coordination that could benefit from nursing case management services. DESIGN: Cross-sectional study. METHODS: Children treated in ambulatory and hospital care in Granada, Spain, with complex chronic diseases in 2016 were analyzed to determine their use of healthcare resources. Socioeconomic variables were evaluated, along with clinical status and duration of their conditions. RESULTS: In total, 265 children were analyzed (mean age 7.3 years, SD 4.63; 56.6% male). The average duration of the disease was 63.26 months (SD 54.09). The most common types of disease were neurological (35.80%), congenital (23.90%), and oncological (18.90%). Multivariate analysis showed that children in need of advanced care (ß = 0.71), with a relatively recent diagnosis (ß = -0.11), with criteria for palliative care 1 (ß = -0.26), and whose mothers were older (ß = 0.36) and had a higher educational level (ß = 0.19) made greater use of healthcare resources during the preceding 12 months, whether urgent or scheduled (r2 = 78.0%, p < .001). CONCLUSIONS: Children with higher needs for advanced care have a heterogeneous use of healthcare resources depending on certain clinical and sociodemographic determinants. This finding highlights the importance of the identification of profiles of children and families for care coordination. The presence of sociodemographic determinants may need individualized approaches to assure a timely health care utilization. CLINICAL RELEVANCE: A significant proportion of the children used multiple health services, being treated at several centers simultaneously, and producing up to 139 total yearly contacts with the health system. Policymakers, healthcare providers, and patients' families should engage in a redesign of healthcare services for these children, providing comprehensive and coordinated systems of care for this population.