Patient-perceived progression in multiple system atrophy: natural history of quality of life.

BACKGROUND: Health-related quality of life (Hr-QoL) scales provide crucial information on neurodegenerative disease progression, help improve patient care and constitute a meaningful endpoint for therapeutic research. However, Hr-QoL progression is usually poorly documented, as for multiple system atrophy (MSA), a rare and rapidly progressing alpha-synucleinopathy. This work aimed to describe Hr-QoL progression during the natural course of MSA, explore disparities between patients and identify informative items using a four-step statistical strategy. METHODS: We leveraged the data of the French MSA cohort comprising annual assessments with the MSA-QoL questionnaire for more than 500 patients over up to 11 years. A four-step strategy (1) determined the subdimensions of Hr-QoL, (2) modelled the subdimension trajectories over time, (3) mapped item impairments with disease stages and (4) identified most informative items. RESULTS: Four dimensions were identified. In addition to the original motor, non-motor and emotional domains, an oropharyngeal component was highlighted. While the motor and oropharyngeal domains deteriorated rapidly, the non-motor and emotional aspects were already impaired at cohort entry and deteriorated slowly over the disease course. Impairments were associated with sex, diagnosis subtype and delay since symptom onset. Except for the emotional domain, each dimension was driven by key identified items. CONCLUSION: The multidimensional Hr-QoL deteriorates progressively over the course of MSA and brings essential knowledge for improving patient care. As exemplified with MSA, the thorough description of Hr-QoL over time using the four-step strategy can provide perspectives on neurodegenerative diseases' management to ultimately deliver better support focused on the patient's perspective.

DeepAlienorNet: A deep learning model to extract clinical features from colour fundus photography in age-related macular degeneration.

OBJECTIVE: This study aimed to develop a deep learning (DL) model, named 'DeepAlienorNet', to automatically extract clinical signs of age-related macular degeneration (AMD) from colour fundus photography (CFP). METHODS AND ANALYSIS: The ALIENOR Study is a cohort of French individuals 77 years of age or older. A multi-label DL model was developed to grade the presence of 7 clinical signs: large soft drusen (>125 µm), intermediate soft (63-125 µm), large area of soft drusen (total area >500 µm), presence of central soft drusen (large or intermediate), hyperpigmentation, hypopigmentation, and advanced AMD (defined as neovascular or atrophic AMD). Prediction performances were evaluated using cross-validation and the expert human interpretation of the clinical signs as the ground truth. RESULTS: A total of 1178 images were included in the study. Averaging the 7 clinical signs' detection performances, DeepAlienorNet achieved an overall sensitivity, specificity, and AUROC of 0.77, 0.83, and 0.87, respectively. The model demonstrated particularly strong performance in predicting advanced AMD and large areas of soft drusen. It can also generate heatmaps, highlighting the relevant image areas for interpretation. CONCLUSION: DeepAlienorNet demonstrates promising performance in automatically identifying clinical signs of AMD from CFP, offering several notable advantages. Its high interpretability reduces the black box effect, addressing ethical concerns. Additionally, the model can be easily integrated to automate well-established and validated AMD progression scores, and the user-friendly interface further enhances its usability. The main value of DeepAlienorNet lies in its ability to assist in precise severity scoring for further adapted AMD management, all while preserving interpretability.

Associations of drusen location with risk factors and incidence of late age-related macular degeneration in the Alienor study.

PURPOSE: To test the hypothesis that central drusen location is strongly linked with known Age-related Macular Degeneration (AMD) risk factors and risk of incident late AMD. METHODS: The Alienor study is a prospective population-based cohort study of residents of Bordeaux, France, followed from 2009 to 2017. On retinal photographs, we defined central drusen as at least one soft drusen (>63 µm) within 500 µm from fovea and pericentral drusen as at least one drusen 500-3000 µm from fovea, in the absence of any central drusen. Late AMD (atrophic and/or neovascular) was diagnosed using multimodal imaging. In total, 481 eyes were included in the analysis: 160 central and 321 pericentral. We investigated associations with systemic (age, sex, smoking, medical prescriptions, plasma concentrations of lipids and nutrients, UV exposure, blood pressure), ocular (retinal thickness, cataract extraction) and genetic risk scores (GRS). RESULTS: In multivariate logistic regression central drusen were associated with smoking (OR, 2.95 for smoking more than 20 pack-years, p = 0.02), HDL-cholesterol (OR, 1.57 for 1 standard deviation (SD) increase, p = 0.0048), pulse pressure (OR, 0.77 for 1 SD increase, p = 0.04), Age-Related Maculopathy Susceptibility 2 (ARMS2) GRS (OR, 1.42; 95% CI, 1.11-1.83) and complement GRS (OR, 1.55; 95% CI, 1.15-2.10). In Cox modelling, the central location of drusen (at baseline or during the follow-up) was associated with a 4.41-fold increased risk (95% CI,1.98-9.81) for an incident late AMD. CONCLUSION: Central drusen were strongly associated with AMD risk factors and incident late AMD, suggesting that it represents a key marker for AMD progression.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Temporal variation in prevalence, awareness and control of hypertension in urban and rural areas in Northeast Brazil between 2006 and 2016 / Variação temporal na prevalência, conhecimento e controle da hipertensão arterial em áreas urbanas e rurais do Nordeste brasileiro entre 2006 e 2016 / Variación temporal de la prevalencia, concienciación y control de la hipertensión en áreas urbanas y rurales en el nordeste brasileño entre 2006 y 2016

Abstract: To assess the evolution in prevalence, awareness and control of hypertension for over 10 years in Pernambuco State, Northeast Brazil, two cross-sectional studies were conducted based on random samples of households in urban and rural areas, in 2006 and 2015/2016, involving adults aged 20 years or older. Hypertension was defined as systolic blood pressure of at least 140mmHg or diastolic blood pressure of at least 90mmHg as well as the reported use of antihypertensive medication. A logistic regression analysis was conducted to estimate the influence of the social, behavioral and anthropometric determinants on hypertension. Although social and behavioral factors improved in this 10-year period, overweight and abdominal obesity increased. Approximately one third of the adult population of Pernambuco had hypertension in 2006 and this prevalence was maintained in 2015/2016. In rural areas, awareness concerning hypertension rose from 44.8% in 2006 to 67.3% in 2015/2016, and control from 5.3% to 27.1%, so that awareness and control were similar in urban and rural areas in 2015/2016. After an adjustment for potential confounding factors, the likelihood of having hypertension more than doubled among men (OR = 2.03; p < 0.001), middle (OR = 4.41; p < 0.001) and old-age subjects (OR = 14.44; p < 0.001), and those who had abdominal obesity (OR = 2.04; p < 0.001) in urban areas and among middle-aged (OR = 2.56; p < 0.001), less educated individuals (OR = 2.21; p = 0.006) and those who were overweight (OR = 2.23; p < 0.001) in rural areas. Despite the favorable evolution in the management of hypertension in Pernambuco, public health measures focused in vulnerable populations are still required, mainly in rural areas, to improve primary prevention and decrease the disease rate.

Resumo: O estudo teve como objetivo avaliar a evolução da prevalência, conhecimento e controle da hipertensão arterial ao longo de 10 anos no Estado de Pernambuco, Nordeste do Brasil. Foram realizados dois estudos transversais em amostras aleatórias em domicílios em áreas urbanas e rurais, em 2006 e 2015/2016, incluindo adultos com 20 anos ou mais. A hipertensão arterial foi definida como pressão sistólica de pelo menos 140mmHg ou pressão diastólica de pelo menos 90mmHg ou o uso referido de medicação anti-hipertensiva. Foi realizada análise de regressão logística para estimar a influência dos determinantes sociais, comportamentais e antropométricos sobre a hipertensão. Os fatores sociais e comportamentais melhoraram ao longo da década em questão, mas as taxas de sobrepeso e de obesidade abdominal aumentaram. Aproximadamente um terço da população adulta de Pernambuco apresentava hipertensão em 2006, e essa prevalência foi mantida em 2015/2016. Nas áreas rurais, o conhecimento da hipertensão aumentou de 44,8% em 2006 para 67,3% em 2015/2016, e o controle aumentou de 5,3% para 27,1%, de maneira que o conhecimento e o controle foram muito semelhantes entre áreas urbanas e rurais em 2015/2016. Após ajustar para potenciais fatores de confusão, a probabilidade de apresentar hipertensão mais do que dobrou entre homens (OR = 2,03; p < 0,001), adultos jovens (OR = 4,41; p < 0,001) e idosos (OR = 14,44; p < 0,001), e entre aqueles com obesidade abdominal (OR = 2,04; p < 0,001) nas áreas urbanas e adultos jovens (OR = 2,56; p < 0,001), pessoas com menor escolaridade (OR = 2,21; p = 0,006) e pessoas com sobrepeso (OR = 2,23; p < 0,001) nas áreas rurais. Apesar da evolução favorável no manejo da hipertensão no Estado de Pernambuco, são necessárias medidas de saúde pública focadas nas populações mais vulneráveis, principalmente nas áreas rurais, para melhorar a prevenção primária e impedir o aumento da hipertensão.

Resumen: El objetivo de este estudio fue evaluar la evolución de la prevalencia, concienciación y control de la hipertensión durante 10 años en el Estado de Pernambuco, Nordeste brasileño. Se llevaron a cabo dos estudios transversales, basados en muestras aleatorias de hogares ubicados en áreas urbanas y rurales, en 2006 y 2015/2016, implicando a adultos con 20 años y más edad. La hipertensión fue definida como presión arterial sistólica de al menos 140mmHg, presión arterial diastólica de al menos 90mmHg, o el consumo informado de medicación antihipertensiva. Se realizó un análisis de regresión logística para estimar la influencia de los determinantes sociales, comportamentales y antropométricos en la hipertensión. Los factores sociales y comportamentales mejoraron durante este período de 10 años, a pesar de que sobrepeso y la obesidad abdominal aumentaron. Aproximadamente un tercio de la población adulta de Pernambuco sufría hipertensión en 2006 y esta prevalencia se mantuvo en 2015/2016. En las áreas rurales, la concienciación sobre la hipertensión aumentó de un 44,8% en 2006, a un 67,3% en 2015/2016, y el control de un 5,3% a un 27,1%, así pues la concienciación y control fueron similares en áreas urbanas y rurales en 2015/2016. Tras el ajuste para los factores potenciales de confusión, la probabilidad de sufrir hipertensión es más del doble entre hombres (OR = 2,03; p < 0,001) de mediana edad (OR = 4,41; p < 0,001) e individuos de edad avanzada (OR = 14,44; p < 0,001), y aquellos que sufrieron obesidad abdominal (OR = 2,04; p < 0,001) en áreas urbanas, y entre los de mediana edad (OR = 2,56; p < 0,001), individuos menos educados (OR = 2,21; p = 0,006) y quienes sufrían sobrepeso (OR = 2,23; p < 0,001) en áreas rurales. A pesar de la evolución favorable en la gestión de la hipertensión en Pernambuco, se necesitan medidas de salud pública que se centren en las poblaciones vulnerables, principalmente en las áreas rurales, para mejorar la prevención primaria y frenar el incremento de la enfermedad.