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Background: There is a need to better understand the rate of cognitive and motor decline of Dementia with Lewy bodies (DLB) and Parkinson's disease Dementia (PDD). Objectives: To compare the rate of cognitive and motor decline in patients with DLB and PDD from the E-DLB Consortium and the Parkinson's Incidence Cohorts Collaboration (PICC) Cohorts. Methods: The annual change in MMSE and MDS-UPDRS part III was estimated using linear mixed regression models in patients with at least one follow-up (DLB n = 837 and PDD n = 157). Results: When adjusting for confounders, we found no difference in the annual change in MMSE between DLB and PDD (-1.8 [95% CI -2.3, -1.3] vs. -1.9 [95% CI -2.6, -1.2] [P = 0.74]). MDS-UPDRS part III showed nearly identical annual changes (DLB 4.8 [95% CI 2.1, 7.5]) (PDD 4.8 [95% CI 2.7, 6.9], [P = 0.98]). Conclusions: DLB and PDD showed similar rates of cognitive and motor decline. This is relevant for future clinical trial designs.
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INTRODUCTION: Reviews of randomized clinical trials (RCTs) in dementia with Lewy bodies (DLB) are essential for informing ongoing research efforts of symptomatic therapies and potentially disease-modifying therapies (DMTs). METHODS: We performed a systematic review of all clinical trials conducted until September 27, 2022, by examining 3 international registries: ClinicalTrials.gov, the European Union Drug Regulating Authorities Clinical Trials Database, and the International Clinical Trials Registry Platform, to identify drugs in trials in DLB. RESULTS: We found 25 agents in 40 trials assessing symptomatic treatments and DMTs for DLB: 7 phase 3, 31 phase 2, and 2 phase 1 trials. We found an active pipeline for drug development in DLB, with most ongoing clinical trials in phase 2. We identified a recent trend towards including participants at the prodromal stages, although more than half of active clinical trials will enroll mild to moderate dementia patients. Additionally, repurposed agents are frequently tested, representing 65% of clinical trials. CONCLUSION: Current challenges in DLB clinical trials include the need for disease-specific outcome measures and biomarkers, and improving representation of global and diverse populations.
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Background: Bacterial meningitis (BM) is a public health challenge as it is associated with high lethality and neurological sequelae. Worldwide, most cases are registered in the African Meningitis Belt (AMB). The role of particular socioepidemiological features is essential for understanding disease dynamics and optimizing policy-making. Objective: To identify socioepidemiological macro-determinants that contribute to explaining the differences in BM incidence between AMB and the rest of Africa. Methods: Country-level ecologic study based on the cumulative incidence estimates of the Global Burden of Disease study and reports of the MenAfriNet Consortium. Data about relevant socioepidemiological features were extracted from international sources. Multivariate regression models were implemented to define variables associated with the classification of African countries within the AMB and the incidence of BM worldwide. Results: Cumulative incidences at the AMB sub-regions were 111.93 (west), 87.23 (central), 65.10 (east), and 42.47 (north) per 100,000 population. A pattern of common origin with continuous exposition and seasonality of cases was observed. Socio-epidemiological determinants contributing to differentiating the AMB from the rest of Africa were household occupancy (OR 3.17 CI 95% 1.09-9.22, p = 0.034) and malaria incidence (OR 1.01 CI 95% 1.00-1.02, p = 0.016). BM cumulative incidence worldwide was additionally associated with temperature and gross national income per capita. Conclusion: Socioeconomic and climate conditions are macro-determinants associated with BM cumulative incidence. Multilevel designs are required to confirm these findings.
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Introducción. Al declararse la pandemia por SARS-CoV-2, se establecieron múltiples cambios en los sistemas de salud y en las instituciones hospitalarias, influyendo en la actividad quirúrgica global. El objetivo de este estudio fue evaluar el impacto de la pandemia en los niveles de autonomía y supervisión operatorias de los residentes de cirugía. Métodos. Estudio analítico cuasi-experimental, que incluyó los procedimientos quirúrgicos registrados por residentes de cirugía general de la Universidad de La Sabana, de febrero de 2019 a agosto de 2021. Se analizaron la autonomía y la supervisión mediante la escala Zwisch en los periodos prepandemia y pandemia. Resultados. Se recolectaron datos de 10.618 procedimientos en el periodo establecido, la mayoría realizados con abordaje abierto (57,4 %) y en rotaciones tronculares de cirugía general (65 %). Los procedimientos realizados más frecuentes fueron apendicectomía (18,6 %), colecistectomía (18,4 %) y herniorrafías (8,6 %). Se encontró una disminución estadísticamente significativa en los niveles globales de autonomía y supervisión entre los periodos analizados de 2, 4/4, 0 a 2, 2/4, 0 (p<0,001). Discusión. La disminución en la autonomía percibida por los residentes podría corresponder al impacto negativo en la motivación intrínseca de los individuos, en la disminución objetiva en el logro de las competencias esperadas en su proceso de formación quirúrgica y a la pérdida del relacionamiento colectivo propiciado por los aislamientos y limitaciones vividos. Conclusión. La pandemia por COVID-19 impactó negativamente en la autonomía y supervisión operatoria de los residentes de cirugía general de la Universidad de La Sabana, Chía, Colombia.
Introduction. Changes in health systems and hospital institutions due to the coronavirus pandemic influenced global surgical activity. The objective of this study was to evaluate the impact of the pandemic on the levels of autonomy and supervision in general surgery residents. Methods. Quasi-experimental analytical study. It included the surgical procedures recorded by general surgery residents of the University of La Sabana from February 2019 to August 2021. Autonomy and supervision were analyzed using the Zwisch scale in the pre-pandemic and pandemic periods. Results. 10,618 procedures were collected in the established period. Most surgeries were performed with an open approach (57,4%), in rotations of general surgery (65%). The most frequent procedures performed were appendectomy (18,6%), and cholecystectomy (18,4%), and herniorrhaphy (8,6%). There was a decrease in levels of autonomy and supervision compared between the analyzed periods from 2, 4/4, 0 to 2, 2/4, 0 (p<0.001). Discussion. The decrease in the autonomy perceived by the residents could correspond to the negative impact on the intrinsic motivation of the individuals, a decrease in the achievement of the competencies expected in their surgical training process, and the loss of the collective relationship produced by the isolation and limitations experienced. Conclusion. The COVID-19 pandemic had a negative impact on autonomy and supervision in general surgery residents of the University of La Sabana, Chia, Colombia
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Humanos , Autonomia Profissional , Infecções por Coronavirus , Cirurgia Geral , Educação Médica , Programas de Pós-Graduação em Saúde , Pandemias , MotivaçãoRESUMO
Introduction. For over a century, Sporothrix schenckii was considered the sole species responsible for sporotrichosis. In 2007, scientific community confirmed the disease could be caused by various Sporothrix species. These species differed in their virulence factors and their antifungal sensitivity. Objective. This study aims to characterize 42 Colombian clinical isolates of Sporothrix spp. phenotypically and genotypically. Materials and methods. Forty-two clinical isolates were characterized using phenotypic methods. It involved various culture media to determine their growth range at different temperatures and to assess the type and distribution of pigment and colony texture. Microscopic morphology was evaluated through microcultures, as well as the conidia diameter, type of sporulation, and morphology. Additionally, the assimilation of carbohydrates was selected as a physiological trait for species identification. Genotyping of 40 isolates was performed through partial amplification of the calmodulin gene, followed by sequence analysis. Results. Molecular studies enabled the identification of 32 isolates of S. schenckii and 8 isolates of S. globosa. The combination of phenotypic and genotypic methods eased these species characterizations and the recognition keys development based on parameters such as growth diameter at 25 and 30 °C, colony texture (membranous or velvety) on potato dextrose agar, and microscopic morphology with predominance of pigmented triangular, elongated oval globose, or subglobose conidia. Conclusions. Confirmation of the phenotypic characteristics and molecular analysis is crucial for identifying Sporothrix species and determining adequate treatment. This study represents the first phenotypical and genotypical characterization of clinical isolates of Sporothrix spp. reported in Colombia.
Introducción. Por más de un siglo se creyó que Sporothrix schenckii era la única especie responsable de la esporotricosis. Sin embargo, en el 2007, se consideró que podría ser causada por diferentes especies de Sporothrix, que difieren en sus factores de virulencia y su sensibilidad a los antifúngicos. Objetivo. Caracterizar fenotípica y genotípicamente 42 aislamientos clínicos colombianos de Sporothrix spp. Materiales y métodos. Se caracterizaron 42 aislamientos clínicos mediante métodos fenotípicos. Se usaron varios medios de cultivo para determinar el rango de crecimiento a diferentes temperaturas, el tipo y la distribución del pigmento, y la textura de las colonias. Se evaluó la morfología microscópica por microcultivos mediante la determinación del diámetro, el tipo de esporulación y la morfología de las conidias. La asimilación de carbohidratos se usó como una característica fisiológica para identificar las especies. La genotipificación de los 40 aislamientos se llevó a cabo mediante la amplificación parcial del gen que codifica para la calmodulina y se confirmó por secuenciación. Resultados. Mediante estudios moleculares, se identificaron 32 aislamientos de S. schenckii y ocho de S. globosa. La combinación de métodos fenotípicos y genotípicos permitió caracterizar las especies y construir claves para su reconocimiento, con base en parámetros como el diámetro de crecimiento a 25 y 30 °C, la textura de las colonias (membranosa, aterciopelada) en agar papa dextrosa y la morfología microscópica con predominio de conidias (triangulares pigmentadas, ovales globosas elongadas, subglobosas). Conclusiones. La caracterización fenotípica y los análisis moleculares son necesarios para identificar las especies de Sporothrix y, de esta forma, elegir el tratamiento indicado. Esta es la primera caracterización fenotípica y genotípica reportada de aislamientos clínicos colombianos de Sporothrix spp.
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Esporotricose , Fenótipo , Sporothrix , GenótipoRESUMO
Identification of factors predicting and driving mortality in PD is important for patient information, disease management, and design of future clinical trials. This study included newly diagnosed PD patients and normal controls (NC) from a population-based study with repeated assessments over a 10-year period. We used the Kaplan-Meier method to estimate survival, Cox proportional hazards regression models to identify baseline risk factors of mortality, and Cox regression models with time-dependent covariates to evaluate the impact of four clinical milestones of advanced PD (visual hallucinations, recurrent falls, dementia, and nursing home placement) on mortality risk. During the 10-year study, 65 (34.2%) of 190 patients and 25 (12.3%) of 203 NC died, with an unadjusted hazard ratio (HR) of 2.85 (95% CI 1.80-4.52) and a HR of 2.48 (95% CI 1.55-3.95) when adjusted for confounders, including comorbidities. Higher age, more severe motor impairment, and postural instability-gait difficulty (PIGD) phenotype were independent baseline predictors of mortality. Each clinical milestone alone more than doubled the risk of death and had a cumulative effect on mortality, with a HR of 10.83 (95% CI 4.39-26.73) in those experiencing all four milestones. PD patients have an increased mortality risk that is disease-related and becomes evident early during the course of the disease. While motor severity and PIGD phenotype were early risk factors of mortality, clinical milestones signaled a substantially increased risk of death later during the disease course, highlighting their potential significance in clinical disease staging and prognosis.
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BACKGROUND/OBJECTIVES: Functional status is one of the most important markers of well-being in older adults, but the drivers of functional decline in dementia are not well known. The aim of our work was to study the association of neuropsychiatric symptoms (NPSs) with functional decline over 5 years in newly diagnosed people with Alzheimer´s disease (AD) and Lewy body dementia (LBD). DESIGN: Secondary analysis of the Dementia Study of Western Norway longitudinal cohort study. SETTING: Multicenter study conducted in memory clinics in western Norway. PARTICIPANTS: We included a total of 196 patients newly diagnosed with AD (n = 111) and LBD (n = 85), followed up annually for 5 years. MAIN OUTCOMES AND MEASURES: The outcome was the rapid disability rating scale (items 1-13). Linear mixed-effects models were used for analysis with the total score of the Norwegian Neuropsychiatric Inventory (NPI) as a predictor measured either at baseline or longitudinally, adjusted for potential confounders, including cognition. Effect modification was checked by introducing interactions with NPI score and stratifying by diagnosis. RESULTS: The total NPI score longitudinal course was associated with functional decline in both AD and LBD. At baseline, the total NPI score predicted functional decline in AD. CONCLUSION: NPSs were associated with the rate of functional decline in people with AD and LBD, independent of cognitive impairment. These results highlight the relevance of early detection and intervention of NPSs, which may also reduce functional decline. J Am Geriatr Soc 68:2257-2263, 2020.
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Doença de Alzheimer/psicologia , Disfunção Cognitiva/diagnóstico , Doença por Corpos de Lewy/psicologia , Desempenho Físico Funcional , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Disfunção Cognitiva/psicologia , Avaliação da Deficiência , Feminino , Avaliação Geriátrica , Humanos , Doença por Corpos de Lewy/fisiopatologia , Modelos Lineares , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Noruega , Avaliação de SintomasRESUMO
In patients with Parkinson's disease (PD), arm swing changes are common, even in the early stages, and these changes are usually evaluated subjectively by an expert. In this article, hypothesize that arm swing changes can be detected using a low-cost, cloud-based, wearable, sensor system that incorporates triaxial accelerometers. The aim of this work is to develop a low-cost, assistive diagnostic tool for use in quantifying the arm swing kinematics of patients with PD. Ten patients with PD and 11 age-matched, healthy subjects are included in the study. Four feature extraction techniques were applied: (i) Asymmetry estimation based on root mean square (RMS) differences between arm movements; (ii) posterior-anterior phase and cycle regularity through autocorrelation; (iii) tremor energy, established using Fourier transform analysis; and (iv) signal complexity through the fractal dimension by wavelet analysis. The PD group showed significant (p < 0.05) reductions in arm swing RMS values, higher arm swing asymmetry, higher anterior-posterior phase regularities, greater "high energy frequency" signals, and higher complexity in their XZ plane signals. Therefore, the novel, portable system provides a reliable means to support clinical practice in PD assessment.
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Acelerometria , Braço , Doença de Parkinson , Dispositivos Eletrônicos Vestíveis , Fenômenos Biomecânicos , Marcha , Humanos , Doença de Parkinson/diagnóstico , Caminhada , PunhoAssuntos
Demência , Doença por Corpos de Lewy , Colômbia , Demência/epidemiologia , Humanos , Corpos de LewyRESUMO
During their journey through the female reproductive tract to reach the oocyte in the ampulla of the fallopian tube, spermatozoa interact with substances and microorganisms that affect sperm quality, thus altering their fertilizing capacity. OBJECTIVES: To determine in vitro the effect of Streptococcus agalactiae, Klebsiella pneumoniae and their soluble factors on sperm parameters, and to evaluate the ability of human sperm to interact with and transport these bacteria. METHODS: The effects of S. agalactiae, K. pneumoniae and their soluble factors on the viability, sperm motility and functional sperm parameters were quantified. In addition, motile spermatozoa were incubated with decreasing concentrations of bacteria for one hour, washed and post-infection treatments were performed with trypsin and transport capacity was assessed by quantitative cultures. RESULTS: Incubation of spermatozoa with K. pneumoniae decreased progressive motility. The soluble factors of K. pneumoniae increased the number of necrotic spermatozoa and the soluble factors of S. agalactiae increased lipid peroxidation of the sperm membrane (p<0.05). A strong interaction between sperm and bacteria was observed in the transport assays even in washed trypsin-treated samples. CONCLUSION: Human spermatozoa act as vectors for infections, generating strong interactions with K. pneumoniae and S. agalactiae favoring their diffusion through the female reproductive tract. This interaction affects male fertility by altering progressive motility, increasing the number of necrotic cells and inducing apoptosis.
Los espermatozoides durante su recorrido por el tracto reproductivo femenino en busca del oocito interactúan con sustancias y microorganismos que afectan la calidad seminal alterando su capacidad fecundante.OBJETIVOS: Determinar el efecto in vitro de Streptococcus agalactiae, Klebsiella pneumoniae y sus factores evaluar la capacidad de los espermatozoides humanos para interactuar y transportar estas bacterias.MÉTODOS: Se cuantificó el efecto de la incubación de S. agalactiae, K. pneumoniae y sus factores solubles sobre la viabilidad, la movilidad y los parámetros espermáticos funcionales. Adicionalmente, espermatozoides móviles fueron incubados con concentraciones decrecientes de bacterias durante una hora, se realizaron lavados y tratamientos post infección con tripsina y se evaluó la capacidad de transporte mediante cultivos cuantitativos.RESULTADOS: La incubación de los espermatozoides con K. pneumoniae ATCC 1705 disminuyó la movilidad espermática tipo I. Los factores solubles de K. pneumoniae ATCC 700603 aumentaron el número de espermatozoides necróticos mientras que los factores solubles de S. agalactiae aumentaron la lipoperoxidación de la membrana espermática (p<0,05). En los ensayos de transporte se observó una interacción fuerte entre los espermatozoides y las bacterias, incluso en las muestras tratadas con tripsina y lavados.CONCLUSIÓN: Los espermatozoides humanos sirven como vectores de infecciones, generan interacciones fuertes con K. pneumoniae y S. agalactiae, favoreciendo su difusión por el tracto reproductivo femenino. Esta interacción afecta la fertilidad masculina alterando la movilidad progresiva, aumentando el número de células necróticas y la apoptosis espermática.