Classic and Atypical Late Infantile Neuronal Ceroid Lipofuscinosis in Latin America: Clinical and Genetic Aspects, and Treatment Outcome with Cerliponase Alfa.

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.

[How to improve community engagement in health: Analysis of proposed actions following the implementation of a community engagement assessment tool]. / ¿Cómo mejoramos la participación comunitaria en salud? Análisis de las acciones propuestas tras la aplicación de una herramienta de evaluación.

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.

[Attend, consult, involve: do we need to redefine the concept of community engagement?] / Asistir, consultar, involucrar: ¿es necesario redefinir el concepto de participación comunitaria?

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.

Evaluating the implementation of community engagement guidelines (EVALUA GPS project): a study protocol.

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.

Association between ankle-brachial index and cognitive function in participants in the PREDIMED-Plus study: cross-sectional assessment.

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.

Community engagement to promote health and reduce inequalities in Spain: a narrative systematic review.

OBJECTIVES: Over the past decade, increasing attention has been paid to community engagement in health (CEH) across Europe. This study aimed to identify and review CEH interventions to promote health and reduce inequalities within the Spanish context and the key facilitators for these community processes. METHODS: A systematic search in six databases, followed by a forward citation search, was conducted to identify implementation literature on CEH in Spain. Articles were included when engagement occurred in at least two stages of the interventions and was not limited to information or consultation of stakeholders. RESULTS: A total of 2023 results were identified; 50 articles were reviewed full text. Five articles were finally selected for inclusion. Data were extracted on various factors including details of the interventions, results achieved, stakeholders involved and their relationships. A narrative synthesis was performed to present results and support the discussion. CONCLUSIONS: Three main points are discussed: the role of professionals and citizens in CEH interventions, providing training to enable a reorientation towards a CEH practice and the relevance of contexts as enablers for community engagement processes to thrive.

Impellent impeller-Switching intra-aortic balloon pump to IMPELLA-CP after ST-segment elevation myocardial infarction and refractory cardiogenic shock.

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.

Obstructive sleep apnoea syndrome and endothelial function: potential impact of different treatment strategies-meta-analysis of prospective studies.

PURPOSE: Previous studies have shown an association between obstructive sleep apnoea syndrome (OSAS) and cardiovascular events. Whether this association is mediated by an impairment of endothelial function, which is itself a driver of elevated cardiovascular risk, has yet to be clarified, as it is the eventual protective role of several OSAS treatments. The aim of our meta-analysis is to evaluate the effect of various OSAS treatments on endothelial function calculated by means of flow-mediated dilatation (FMD). METHODS: We conducted a meta-analysis of prospective studies including patients affected by mild to severe OSAS treated with continuous positive airway pressure (CPAP), surgery, oral appliance and medical treatments. FMD was measured before and after treatment RESULTS: After pooling results from different treatment strategies, OSAS treatment showed a positive impact on endothelial function (Mean Difference [MD] = 2.58; 95% CI 1.95-3.20; p < 0.00001). CONCLUSIONS: Our study supports the hypothesis that several modalities of treatment for OSAS positively impact endothelial function. Whether this effect also associates with an improvement of clinical outcomes remains to be ascertained.

Presence of acute and chronic renal failure in patients with paroxysmal nocturnal hemoglobinuria: results of a retrospective analysis from the Spanish PNH Registry.

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.

On-Line HPLC-UV-mass spectrometry and tandem mass spectrometry for the rapid delineation and characterization of differences in complex mixtures: a case study using toxic oil variants.

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.