Assessment of plasma chitotriosidase activity, CCL18/PARC concentration and NP-C suspicion index in the diagnosis of Niemann-Pick disease type C: A prospective observational study

Background: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive neurodegenerative disease caused by mutations in either the NPC1 or NPC2 genes. The diagnosis of NP-C remains challenging due to the non-specific, heterogeneous nature of signs/symptoms. This study assessed the utility of plasma chitotriosidase (ChT) and Chemokine (C-C motif) ligand 18 (CCL18)/pulmonary and activation-regulated chemokine (PARC) in conjunction with the NP-C suspicion index (NP-C SI) for guiding confirmatory laboratory testing in patients with suspected NP-C. Methods: In a prospective observational cohort study, incorporating a retrospective determination of NP-C SI scores, two different diagnostic approaches were applied in two separate groups of unrelated patients from 51 Spanish medical centers (n = 118 in both groups). From Jan 2010 to Apr 2012 (Period 1), patients with =2 clinical signs/symptoms of NP-C were considered ''suspected NP-C'' cases, and NPC1/NPC2 sequencing, plasma chitotriosidase (ChT), CCL18/PARC and sphingomyelinase levels were assessed. Based on findings in Period 1, plasma ChT and CCL18/PARC, and NP-C SI prediction scores were determined in a second group of patients between May 2012 and Apr 2014 (Period 2), and NPC1 and NPC2 were sequenced only in those with elevated ChT and/or elevated CCL18/PARC and/or NP-C SI =70. Filipin staining and 7-ketocholesterol (7-KC) measurements were performed in all patients with NP-C gene mutations, where possible. Results: In total across Periods 1 and 2, 10/236 (4%) patients had a confirmed diagnosis o NP-C based on gene sequencing (5/118 4.2%] in each Period): all of these patients had two causal NPC1 mutations. Single mutant NPC1 alleles were detected in 8/236 (3%) patients, overall. Positive filipin staining results comprised three classical and five variant biochemical phenotypes. No NPC2 mutations were detected. All patients with NPC1 mutations had high ChT activity, high CCL18/PARC concentrations and/or NP-C SI scores =70. Plasma 7-KC was higher than control cut-off values in all patients with two NPC1 mutations, and in the majority of patients with single mutations. Family studies identified three further NP-C patients. Conclusion: This approach may be very useful for laboratories that do not have mass spectrometry facilities and therefore, they cannot use other NP-C biomarkers for diagnosis

Role of age and comorbidities in mortality of patients with infective endocarditis

Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015. Patients were stratified into three age groups:<65 years, 65 to 80 years, and = 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 = 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients =80 years who underwent surgery were significantly lower compared with other age groups (14.3%, 65 years; 20.5%, 65-79 years; 31.3%, =80 years). In-hospital mortality was lower in the <65-year group (20.3%, <65 years;30.1%, 65-79 years;34.7%, =80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%, =80 years; p = 0.003).Independent predictors of mortality were age = 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI = 3 (HR:1.62; 95% CI:1.39–1.88), and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared, the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. Conclusion: There were no differences in the clinical presentation of IE between the groups. Age = 80 years, high comorbidity (measured by CCI), and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

Between Governance-Driven Democratisation and Democracy-Driven Governance: explaining changes in Participatory Governance in the Case of Barcelona

Scholars of participatory democracy have long noted dynamic interactions and transformations within and between political spaces that can foster (de)democratisation. At the heart of this dynamism lie (a) the processes through which top‐down “closed” spaces can create opportunities for rupture and democratic challenges and (b) vice‐versa, the mechanisms through which bottom‐up, open spaces can be co‐opted through institutionalisation. This paper seeks to unpick dynamic interactions between different spaces of participation by looking specifically at two forms of participatory governance, or participatory forms of political decision making used to improve the quality of democracy. First, Mark Warren's concept of ‘governance‐driven democratization’ describes top‐down and technocratic participatory governance aiming to produce better policies in response to bureaucratic rationales. Second, we introduce a new concept, democracy‐driven governance, to refer to efforts by social movements to invent new, and reclaim and transform existing, spaces of participatory governance and shape them to respond to citizens’ demands. The paper defines these concepts and argues that they co‐exist and interact in dynamic fashion; it draws on an analysis of case study literature on participatory governance in Barcelona to illuminate this relationship. Finally, the paper relates the theoretical framework to the case study by making propositions as to the structural and agential drivers of shifts in participatory governance

The influence of alcohol intake in myopia development or progression: The SUN cohort study

Background: Myopia is a highly prevalent disorder, and one of the first causes of blindness. In turn, alcohol consumption has been shown to be a risk factor for many diseases and a main contributor to the global burden of disease. However, no studies have investigated the relationship between alcohol intake and myopia. Our aim was to prospectively assess the association between alcohol intake and the development or progression of myopia. Methods: In a Spanish dynamic prospective cohort (the SUN Project) we assessed 15,642 university graduates, recruited between 1999 and 2018 and followed up biennially through mailed questionnaires. Alcohol intake was assessed with a validated 136-item food frequency questionnaire. Development or progression of myopia was collected in subsequent questionnaires during follow-up every two years. Results: Alcohol intake was linearly and significantly associated with a higher risk of myopia development or progression: the OR for 10-year incidence/progression of myopia was 1.05, 95% CI 1.01–1.09 per each 10-grams increase in alcohol intake. Conclusions: Alcohol consumption might lead to the development or progression of myopia, although confir- mation is needed for the mechanisms through which this association may occur, thus further research is needed to verify these finding

The influence of alcohol intake in myopia development or progression: The SUN cohort study

Background: Myopia is a highly prevalent disorder, and one of the first causes of blindness. In turn, alcohol consumption has been shown to be a risk factor for many diseases and a main contributor to the global burden of disease. However, no studies have investigated the relationship between alcohol intake and myopia. Our aim was to prospectively assess the association between alcohol intake and the development or progression of myopia. Methods: In a Spanish dynamic prospective cohort (the SUN Project) we assessed 15,642 university graduates, recruited between 1999 and 2018 and followed up biennially through mailed questionnaires. Alcohol intake was assessed with a validated 136-item food frequency questionnaire. Development or progression of myopia was collected in subsequent questionnaires during follow-up every two years. Results: Alcohol intake was linearly and significantly associated with a higher risk of myopia development or progression: the OR for 10-year incidence/progression of myopia was 1.05, 95% CI 1.01–1.09 per each 10-grams increase in alcohol intake. Conclusions: Alcohol consumption might lead to the development or progression of myopia, although confir- mation is needed for the mechanisms through which this association may occur, thus further research is needed to verify these finding

Role of age and comorbidities in mortality of patients with infective endocarditis

[eng] Purpose: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Methods: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. Results: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. Conclusion: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group