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The endogenous dynorphin/kappa opioid receptor (KOR) system in the brain mediates the dysphoric effects of stress, and KOR antagonists may have therapeutic potential for the treatment of drug addiction, depression, and psychosis. One class of KOR antagonists, the long-acting norBNI-like antagonists, have been suggested to act by causing KOR inactivation through a cJun-kinase mechanism rather than by competitive inhibition. In this study, we screened for other opioid ligands that might produce norBNI-like KOR inactivation and found that nalfurafine (a G-biased KOR agonist) and nalmefene (a KOR partial agonist) also produce long-lasting KOR inactivation. Neither nalfurafine nor nalmefene are completely selective KOR ligands, but KOR inactivation was observed at doses 10-100 fold lower than necessary for mu opioid receptor actions. Daily microdosing with nalfurafine or nalmefene blocked KORs responsible for antinociceptive effects, blocked KORs mediating stress-induced aversion, and mitigated the aversion during acute and protracted withdrawal in fentanyl-dependent mice. Both nalfurafine and nalmefene have long histories of safety and use in humans and could potentially be repurposed for the treatment of dynorphin-mediated stress disorders., Competing Interests: Competing Interest Statement: The authors declare no conflicts of interest.

Objective: To analyse the lines of action identified in the health promotion projects participating in the EvaluA GPS research, and their relationship with the scores assigned in EvalGuia, a tool for evaluating evidence-based community participation., Design: Qualitative-quantitative multicentre study., Setting: Primary care or intersectoral network of primary care and municipalities in five autonomous communities in Spain., Participants: Participants of 10 health promotion projects, selected with convenience sampling, following inclusion criteria (projects with a minimum of community engagement and centred on community health)., Method: Data were collected through questionnaires (EvalGuía tool) and participatory workshops. Quantitative data were analysed with descriptive statistics, qualitative data were analysed using matrix analysis., Results: After implementing the EvalGuide tool, the lowest scores were assigned in outcome evaluation, knowledge of policies related to community participation, diversity in the core working group, inclusivity policies, financial resources and diffusion of results. The lines of action proposed were heterogeneous and did not always match with those prioritised as lower score. The prioritised lines revolved around project organisation and communication., Conclusions: The EvalGuide tool can be helpful to design action plans in Health Promotion projects. The implementation of measures in 12 months to increase the diversity of the core working group, to incorporate work-life balance measures or to improve evaluation is difficult. More time is needed to implement such measures., (Copyright © 2023 The Authors. Publicado por Elsevier España S.L.U. All rights reserved.)

Introduction: Late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), is a neurodegenerative autosomal recessive disease caused by TPP1 gene variants , with a spectrum of classic and atypical phenotypes. The aim of treatment is to slow functional decline as early as possible in an attempt to improve quality of life and survival. This study describes the clinical characteristics as well as the response to treatment with cerliponase alfa., Materials and Methods: A retrospective study was conducted in five Latin-American countries, using clinical records from patients with CLN2. Clinical follow-up and treatment variables are described. A descriptive and bivariate statistical analysis was performed., Results: A total of 36 patients were observed (range of follow-up of 61-110 weeks post-treatment). At presentation, patients with the classic phenotype ( n  = 16) exhibited regression in language (90%), while seizures were the predominant symptom (87%) in patients with the atypical phenotype ( n  = 20). Median age of symptom onset and time to first specialized consultation was 3 (classical) and 7 (atypical) years, while the median time interval between onset of symptoms and treatment initiation was 4 years (classical) and 7.5 (atypical). The most frequent variant was c.827 A > T in 17/72 alleles, followed by c.622C > T in 6/72 alleles. All patients were treated with cerliponase alfa, and either remained functionally stable or had a loss of 1 point on the CLN2 scale, or up to 2 points on the Wells Cornel and Hamburg scales, when compared to pretreatment values., Discussion and Conclusion: This study reports the largest number of patients with CLN2 currently on treatment with cerliponase alfa in the world. Data show a higher frequency of patients with atypical phenotypes and a high allelic proportion of intron variants in our region. There was evidence of long intervals until first specialized consultation, diagnosis, and enzyme replacement therapy. Follow-up after the initiation of cerliponase alfa showed slower progression or stabilization of the disease, associated with adequate clinical outcomes and stable functional scores. These improvements were consistent in both clinical phenotypes., Competing Interests: Dr. Atanacio has been a lecturer for the Biomarin Laboratory. Dr. Denzler has been a speaker for BioMarin. Dr. Durand has maintained a financial relationship with BioMarin through service contracts as speaker. Dr. Erlane has received travel grants, speaker fees, and educational grants from Biomarin. Dr. Espitia Segura reports a relationship with BioMarin Pharmaceutical Inc., including speaker fees and travel reimbursement. Dr. N Guelbert has received speaker fees from Biomarin. Dr. Pessoa has been a speaker for Biomarin. Dr. Naranjo and Dr. Tavera report a relationship with BioMarin Pharmaceutical Inc. that includes speaker and conference fees, as well as travel reimbursement., (© 2024 The Authors.)

Objective: To describe how a sample of people working in community health promotion projects perceive and implement community engagement approaches., Method: Mixed qualitative-quantitative study. Data was collected through: semi-structured interviews with 10 people representing the projects, and workshops in which 53 people participated and responded to a questionnaire prepared ad hoc to identify levels of community engagement. Descriptive statistical analysis of the questionnaires and framework analysis of the interviews, observations and workshops recordings., Results: Although the projects are described as highly participatory, community engagement appeared mainly in the form of attending events, with few examples of consultation or community involvement., Conclusions: This difference may be due to the lack of a culture of participation, both in individuals and institutions, and lack of training in community engagement. It is proposed to change the language from participation-attendance to using expressions such as consulting or involving people., (Copyright © 2023 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The EVALUA GPS project aims to evaluate the impact of the implementation of the National Institute for Health Care and Excellence (NICE) guideline 'Community engagement: improving health and well-being and reducing health inequalities' adapted to the Spanish context., Methods and Analysis: Phase I: A tool will be designed to evaluate the impact of implementing the recommendations of the adapted NICE guideline. The tool will be developed through a review of the literature on implementation of public health guidelines between 2000 and 2021 and an expert's panel consensus., Phase Ii: The developed tool will be implemented in 16 community-based programmes, acting as intervention sites, and 4 controls through a quasi-experimental pre-post study. Phase III: A final online web tool, based on all previously collected information, will be developed to support the implementation of the adapted NICE guidelines recommendations in other contexts and programmes., Data Collection and Analysis: Data will be collected through surveys and semistructured interviews. Quantitative and qualitative data will be analysed to identify implementation scenarios, changes in community engagement approaches, and barriers and facilitators to the implementation of the recommendations. All this information will be further synthesised to develop the online tool., Ethics and Dissemination: The proposed research has been approved by the Clinical Research Ethics Committee of Aragon. Results will be presented at national and international conferences and published in peer-reviewed open access journals. The interactive online tool (phase III) will include examples of its application from the fieldwork., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction and Objectives: The ankle-brachial index (ABI) is an indicator of peripheral artery disease (PAD). The aim of this study was to assess the association between PAD, measured with the ABI, and cognitive function in persons with overweight or obesity and metabolic syndrome., Methods: Cross-sectional study conducted with baseline data from the PREDIMED-Plus study, which included 4898 participants (after exclusion of those without ABI measurements) aged between 55 and 75 years, and with overweight or obesity and metabolic syndrome. At the baseline assessment, we measured the ABI with a standardized protocol and assessed the presence of other cardiovascular risk factors (eg, diabetes, dyslipidemia, hypertension). Cognitive function was evaluated using several tests validated for the Spanish population (mini-mental state examination [MMSE], phonological and semantic verbal fluency test, WAIS-III working memory index [WMI], parts A and B of the trail making test (TMT), and clock drawing test). Generalized linear models were used to assess the association between the ABI and cognitive function., Results: Among the participants, 3.4% had PAD defined as ABI ≤ 0.9, and 3.3% had arterial calcification defined as ABI ≥ 1.4. PAD was associated with age, systolic blood pressure and obesity indicators, while arterial calcification was also associated with obesity and diabetes. No significant associations were observed between cognitive function and ABI or PAD., Conclusions: In our sample, the presence of PAD increased with age, blood pressure, and obesity. No significant association was observed between ABI, PAD, or cognitive function., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Cardiogenic shock is a dreadful complication of myocardial infarction. Despite widespread use and availability, intra-aortic balloon pump (IABP) does not reduce mortality nor improves outcomes. Advanced mechanical circulatory support with IMPELLA system can substantially support hemodynamics and improve short-term prognosis in patients with myocardial infarction and cardiogenic shock., Competing Interests: None declared.

Objective: To determine the number of potential deceased organ donors from out-of- hospital cardiac arrest cases (OHCA) attended by public physician-led emergency medical services in Spain, based on data recorded in the nationwide Spanish OHCA Registry (OHSCAR)., Material and Methods: We analysed OHSCAR data on deceased OHCA patients in Spain during 13 months (1/10/2013 to 31/10/2014). Variables included age, sex, estimated OHCA time, cardiopulmonary resuscitation (CPR) start time and outcome. Inclusion criteria were: age 16-60 years, witnessed OHCA, no return of spontaneous circulation (ROSC) and time interval <15min between OHCA occurrence and CPR initiation., Results: Of a total 8789 cases, 3290 met the age criteria; of these, CPR was not witnessed in 745 cases. Among the remaining 2545 patients, 141 were included in uncontrolled donation after cardiac death (uDCD) programs, 902 arrived at the hospital with ROSC, 64 arrived with ongoing CPR and 15 cases were lost to follow-up. Of the remaining 1423 without ROSC, CPR initiation time was not recorded in 454 cases and 398 did not meet the time criteria <15min between OHCA and CPR initiation. Finally, 571 met all the criteria and could have been potential donors. There were significant differences in the actual donors percentage from potential donors percentage between provinces with and without donor programs (141/322=43.8% versus 0/390=0%), but there were no differences in ROSC between the two types of provinces (418/1320=31.7% versus 652/1970=33.4%)., Conclusions: Many potential donors are missed in current clinical practice. uDCD programs are few and underused even in a country with high rates of organ transplantation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disease. With the advent of eculizumab treatment, renal function has substantially improved, although no data from real-world clinical practice are available. An observational, retrospective, multicenter study was conducted in Spain on clinical data obtained from outpatient visits of patients with PNH (Spanish PNH Registry) who had experienced acute (ARF) or chronic (CRF) renal failure. Of the 128 patients registered (April 2014), 60 were diagnosed with classic PNH. Twenty-seven (45.0%) patients with a mean age of 48.5 (±16.2) years had renal failure, ARF or CRF, and were included in this study. Near half of the patients (n = 13; 48.1%) presented with ARF alone, 33.3% (n = 9) had CRF with episodes of ARF, while 18.5% (n = 5) were diagnosed with CRF alone. For patients with diagnosis of PNH and renal failure (n = 27), the median time to the first ARF episode was 6.5 (CI 95%; 2.2, 14.9) years, whereas the median to the diagnosis of CRF was 14.5 (CI 95%; 3.8, 19.2) years after the diagnosis of PNH. Patients with ARF (n = 22) were treated with eculizumab and did not experience new episodes of ARF, except for one patient with sepsis. Of the patients with CRF, two received treatment without experiencing further episodes of ARF. Sixteen patients who completed treatment (11 with ARF and 5 with ARF + CRF) recovered from the episode of ARF or from CRF. Of the remaining patients treated with eculizumab, one patient improved from stages III to II, three patients stabilized without showing disease progression, and one patient progressed from stages III to IV. Treatment with eculizumab in PNH patients has beneficial effects on renal function, preventing ARF and progression to CRF.

Most survival outcomes in out-of-hospital cardiac arrest (OHCA) are provided by emergency medical services (EMS) without a doctor on board. Our objective was to determine such outcomes in a whole country with public physician-led EMS., Methods: We analyzed data from a nationwide prospective registry of OHCA cases attended by 19 public EMS in Spain, covering the period from 1-October 2013 to 30-October 2014., Results: Advanced life support (ALS) was initiated in 9347 cases (incidence 18.6 cases/10 5 inhabitants per year). Resuscitation was considered futile in 558 cases (5.9%), and ALS was continued in 8789 cases (94.1%); mean age 63.5±17 years, 72.1% men. Initial rhythm was shockable in 22.1% of cases. Basic life support (BLS) was provided by bystanders in 1602 (24%) cases (635 of them with telephone assistance from the dispatch center). Of 8789 patients receiving ALS, 72.1% men, 2669 (30.4%) patients had return of spontaneous circulation on hospital arrival, 50.6% when the initial rhythm was shockable. Hospital discharge with good neurological status (CPC 1-2 ) was found in 11.1% of the study population and in 27.6% when considering the Utstein comparator group of patients. A total of 216 (2.5%) patients arrived at the hospital with ongoing resuscitation, of whom only one survived with CPC 1-2 , and 165 (1.9%) patients were included in non-heart-beating donation programs., Conclusions: In Spain with physician-led EMS, OHCA survival with CPC 1-2 reached a reasonable percentage despite only a modest contribution of bystander BLS. Ongoing resuscitation strategy seems to be futile except when considering non-heart beating donation programs., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To determine the current epidemiological situation, prevention and management of child and youth obesity based on the best scientific evidence available., Methodology: Literature search in PubMed, Cochrane, Science Direct, ENFISPO, Lilacs and SciELO, selecting articles about child and youth obesity, its prevention and treatment., Results: Child and youth obesity is a multifactorial chronic disease that it has been increasing, tending to stay in adolescence and adulthood with greater intensity than more early starts. The data vary from country to country, although most articles are governed by body mass index (BMI). Pediatric overweight is defined by a BMI percentiles located between 91-98 and obesity by a percentile equal or greater than 99. Its prevalence varies according to time, geography, age, gender and race. The prevalence rates of obesity in Spain are one of the highest around the world. The overweight prevalence is lower slightly and there is no difference in gender. Its implications include the metabolic syndrome and diabetes mellitus II. Unanimously, the combination of interventions on life and dietary habits and physical activity is important for the management of obesity and overweight., Conclusion: Currently, the obesity management requires a generalized approach, with changes in lifestyle, diet and physical activity. The best solution for reducing this epidemic lies in prevention rather than treatment.

Mediastinitis is a complication generally associated with thoracic surgery. Its occurrence after placement of a central venous catheter is uncommon, and only a few cases have been reported. An 83-year-old man who had mediastinitis due to extravasation of parenteral nutritional formula via a central venous catheter is presented. The signs and symptoms, diagnosis, and treatment of this unusual complication are described. This complication should be included in the differential diagnosis of mediastinitis in patients with a central venous catheter in place who have not had thoracic surgery.

An integrated differential approach to the characterization of complex mixtures is presented which includes the targeting of liquid chromatography (LC) peaks for identification using characteristic UV adsorption of the LC peak, subsequent molecular weight and formula determination using accurate mass LC mass spectrometry (MS), and structure characterization using accurate mass LC-tandem mass spectrometry. The use of differential UV adsorption aids in narrowing the scope of the study to only specific peaks of interest. Accurate mass measurement of the molecular ion species provides molecular weight information as well as atomic composition information. The tandem MS (MS/MS) spectra provide fragmentation information which allows for structural characterization of each component. Accurate mass assignment of each of the fragment ions in the MS/MS spectrum provides atomic composition for each of the fragment ions and thus further aids in the structural characterization. These experiments are facilitated through the use of on-line LC-MS and LC-MS/MS with in-line UV detection. A synthetic toxic oil (STO) related to Toxic Oil Syndrome is studied with a focus on possible contaminants resulting from the interaction of aniline, used as a denaturant, with the normal components of the oil. A differential analysis between the STO and a control oil is performed. LC peaks were targeted using UV absorbance to indicate the possible presence of the aniline moiety. Further differential analysis was performed through the determination of the MS signals associated with each component separated on the LC. Finally, the MS/MS data was also used to determine if the fragmentation of the targeted components indicated the presence of aniline. The MS/MS and accurate mass data were used to assign the structures for the targeted components., (Copyright 2002 John Wiley & Sons, Ltd.)

Aims and Background: The role of radiotherapy in the management of patients with optic pathway tumors remains controversial. This study analyzes the outcome of patients treated with radiotherapy and attempts to identify the groups of patients that may require early therapy., Methods: We retrospectively reviewed 36 patients with optic pathway tumors treated with radiotherapy alone (26 patients) or with postoperative radiotherapy (10 patients). Seven patients had optic nerve tumors and 29 patients had chiasmal tumors. The actuarial progression free survival and observed survival probabilities were calculated using the Kaplan-Meier method and differences between curves were evaluated by the Mantel-Cox test. The obtained significant variables in the univariate analysis were analyzed using the Cox proportional hazards model., Results: The 10-year actuarial progression-free survival (10-y PFS) rate was 86% for patients with optic nerve gliomas and 47% for patients with chiasmal tumors. The 10-year actuarial observed survival (10-y OS) rate was 75% for patients with optic nerve gliomas and 53% for patients with chiasmal gliomas. In the group of patients with chiasmal tumors, progression-free survival and observed survival rates were significantly lower in infants (10-y PFS: 30%; 10-y OS: 37%), in patients with neurological deficits (10-y PFS and 10-y OS: 23%), in patients with signs of elevated intracranial pressure (10-y PFS and 10-y OS: 9%), with hydrocephalus (10-y PFS and 10-y OS: 0%), or with impairment of consciousness (10-y PFS and 10-y OS: 17%). Evaluation by computed tomography scanning was associated with a significantly higher probability of PFS. Radiation doses lower than 50 Gy were associated with significantly lower PFS and OS rates. In the Cox multivariate analysis, presence of neurological deficits and radiation dose significantly influenced observed survival. Presence of hydrocephalus significantly influenced progression-free survival., Conclusions: The prognosis of patients with chiasmal gliomas presenting with neurologic deficits is poor and should be treated at diagnosis. A minimum tumor dose of 50 Gy is recommended.