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1.
Postgrad Med J ; 97(1151): 566-570, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32788311

RESUMEN

OBJECTIVES: Motor neuron disease (MND) is a neurodegenerative disorder leading to functional decline and death. Multidisciplinary MND clinics provide an integrated approach to management and facilitate discussion on advanced care directives (ACDs). The study objectives are to analyse (1) the prevalence of ACD in our MND clinic, (2) the relationship between ACD and patient demographics and (3) the relationship between ACD decision-making and variables such as NIV, PEG, hospital admissions and location of death. METHODS: Using clinic records, all patients who attended the MND clinic in Liverpool Hospital between November 2014 and November 2019 were analysed. Data include MND subtypes, symptom onset to time of diagnosis, time of diagnosis to death, location and reason of death. ACD prevalence, non-invasive ventilation (NIV) and percutaneous endoscopic gastrostomy (PEG) requirements were analysed. RESULTS: There were 78 patients; M:F=1:1. 44 (56%) patients were limb onset, 28 (36%) bulbar onset, 4 primary lateral sclerosis and 2 flail limb syndrome presentations. 27% patients completed ACDs, while 32% patients declined ACDs. Patients born in Australia or in a majority English-speaking country were more likely to complete ACDs compared to those born in a non-English-speaking country. There was no significant correlation between ACD completion and age, gender, MND subtype, symptom duration, NIV, PEG feeding, location of death. CONCLUSION: One-quarter of patients completed ACDs. ACDs did not correlate with patient age, gender, MND subtype and symptom duration or decision-making regarding NIV, PEG feeding or location of death. Further studies are needed to address factors influencing patients' decisions regarding ACDs.


Asunto(s)
Planificación Anticipada de Atención/estadística & datos numéricos , Directivas Anticipadas/estadística & datos numéricos , Enfermedad de la Neurona Motora/epidemiología , Planificación Anticipada de Atención/organización & administración , Directivas Anticipadas/psicología , Anciano , Anciano de 80 o más Años , Australia/epidemiología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/terapia , Prevalencia , Estudios Retrospectivos
2.
Emerg Med Australas ; 34(6): 884-891, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35701386

RESUMEN

OBJECTIVES: The pericapsular nerve group (PENG) block was first described for analgesia of hip fracture in 2018. We hypothesised that the PENG block is safe and effective for patients with hip fracture when provided by emergency physicians and trainees in the ED. METHODS: This was an observational study of routine care. Consecutive patients receiving regional anaesthesia for hip fracture at a single ED were prospectively enrolled. Pain scores were assessed prior to regional anaesthesia then at 15, 30 and 60 min after administration. Maximal reduction in pain scores within 60 min were assessed using the Visual Analogue Scale (at rest and on movement) or the Pain Assessment IN Advanced Dementia tool (at rest). Patients were followed for opioid use for 12 h after regional anaesthesia and adverse events over the duration of admission. RESULTS: There were 67 eligible patients during the enrolment period, with 52 (78%) prospectively enrolled. Thirty-three received femoral blocks (19 fascia iliaca compartment blocks, 14 femoral nerve blocks) and 19 received a PENG block. Inexperienced providers were able to successfully perform the PENG block. There was no difference in maximum pain score reduction between the groups. There was no difference in adverse effects between groups. Opioid use was similar between the groups. More patients were opioid-free after a PENG block. CONCLUSIONS: The present study demonstrated that the PENG block can be provided safely and effectively to patients with hip fracture in the ED. On the basis of this pilot study, a larger randomised controlled study should now be designed.


Asunto(s)
Nervio Femoral , Fracturas de Cadera , Humanos , Estudios de Cohortes , Proyectos Piloto , Fracturas de Cadera/cirugía , Dolor , Servicio de Urgencia en Hospital
3.
J Diabetes ; 12(2): 151-157, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31373771

RESUMEN

BACKGROUND: Gestational diabetes mellitus (GDM) and caesarean deliveries independently increase the risk of postoperative complications. There are limited data on the influence of insulin use on the outcomes of neonates who were delivered via caesarean section. We sought to investigate the impact of insulin use in women with GDM on resuscitation rates of infants post caesarean delivery. METHODS: A retrospective database review of women with singleton term (≥ 37 weeks) pregnancies who were on insulin for GDM delivering between January 2005 and December 2014 at a major metropolitan hospital in Sydney. RESULTS: One thousand eight hundred and fifty-seven women with GDM were identified. The mean age was 31.01 ± 5.63 years and mean gestational period of 39.07 ± 1.00 weeks. 31.0% received insulin treatment for GDM. Women who were on insulin were older (31.9 ± 5.7 vs 30.6 ± 5.6 years, P < 0.001), had a higher body mass index (BMI) (31.2 ± 7.7 vs 29.0 ± 7.4 kg/m2, P < 0.001), higher rates of preeclampsia (7.3% vs 4.1%, P = 0.004), lower rates of alcohol consumption (0.4% vs 1.7%, P = 0.014), and had infants with lower resuscitation rates (21.2% vs 28.6%, P = 0.001). Infants who required resuscitation had a lower gestational age, lower five-minute APGAR score, and lower birth weight, length, and head circumferences. On multivariate analysis, women with GDM treated with insulin (odds ratio [OR] = 0.69, CI = 0.54-0.89, P = 0.004), higher gestational age (OR = 0.88, CI = 0.78-0.99, P = 0.032), higher maternal BMI (OR = 1.02, CI = 1.01-1.04, P = 0.005), and emergency caesarean (OR = 2.33, CI = 1.74-3.12, P < 0.001) independently predicted incidence of resuscitation. CONCLUSIONS: The findings suggest a relationship between insulin use and reduced resuscitation rates of infants born from mothers with GDM. Further studies investigating the role, dosage, and criteria for insulin use in women with GDM are required.


Asunto(s)
Reanimación Cardiopulmonar/estadística & datos numéricos , Cesárea/efectos adversos , Diabetes Gestacional/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Adulto , Femenino , Humanos , Recién Nacido , Embarazo , Síndrome de Dificultad Respiratoria del Recién Nacido , Estudios Retrospectivos
4.
Sci Rep ; 7(1): 12441, 2017 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-28963553

RESUMEN

Post-stroke cognitive impairment (PSCI) warrants early detection and management. We sought to develop a risk score for screening patients at bedside for risk of delayed PSCI. Ischemic stroke survivors with PSCI and no cognitive impairments (NCI) 3-6 months post-stroke were studied to identify candidate variables predictive of PSCI. These variables were used to develop a risk score using regression models. The score, and the best identified clinical cutoff point, underwent development, stability testing, and internal and external validation in three independent cohorts from Singapore and Hong Kong. Across 1,088 subjects, the risk score, dubbed CHANGE, had areas under the receiver operating characteristics curve (AUROC) from 0.74 to 0.82 in detecting significant risk for PSCI, and had predicted values following actual prevalence. In validation data 3-6 and 12-18 months post-stroke, subjects with low, medium, and high scores had PSCI prevalence of 7-23%, 25-58%, and 67-82%. CHANGE was effective in screening ischemic stroke survivors for significant risk of developing PSCI up to 18 months post-stroke. CHANGE used readily available and reliable clinical data, and may be useful in identifying at-risk patients for PSCI.


Asunto(s)
Isquemia Encefálica/diagnóstico , Disfunción Cognitiva/diagnóstico , Accidente Cerebrovascular/diagnóstico , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Isquemia Encefálica/complicaciones , Isquemia Encefálica/fisiopatología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Estudios de Cohortes , Diagnóstico Precoz , Femenino , Hong Kong , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Curva ROC , Análisis de Regresión , Proyectos de Investigación , Factores de Riesgo , Singapur , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/fisiopatología
5.
Neuroimage Clin ; 14: 37-42, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28116240

RESUMEN

OBJECTIVE: Hippocampal atrophy has been associated with mild cognitive impairment (MCI) in Parkinson's disease (PD). However, literature on how hippocampal atrophy affects the pathophysiology of cognitive impairment in PD has been limited. Previous studies assessed the hippocampus as an entire entity instead of their individual subregions. We studied the progression of cognitive status in PD subjects over 18 in relation to hippocampal subfields atrophy. METHODS: 65 PD subjects were included. Using the MDS task force criteria, PD subjects were classified as either having no cognitive impairment (PD-NCI) or PD-MCI. We extended the study by investigating the hippocampal subfields atrophy patterns in those who converted from PD-NCI to PD-MCI (PD-converters) compared to those who remained cognitively stable (PD-stable) over 18 months. Freesurfer 6.0 was used to perform the automated segmentation of the hippocampus into thirteen subregions. RESULTS: PD-MCI showed lower baseline volumes in the left fimbria, right CA1, and right HATA; and lower global cognition scores compared to PD-NCI. Baseline right CA1 was also correlated with baseline attention. Over 18 months, decline in volumes of CA2-3 and episodic memory were also seen in PD-converters compared to PD-stable. Baseline volumes of GC-DG, right CA4, left parasubiculum, and left HATA were predictive of the conversion from PD-NCI to PD-MCI. CONCLUSION: The findings from this study add to the anatomical knowledge of hippocampal subregions in PD, allowing us to understand the unique functional contribution of each subfield. Structural changes in the hippocampus subfields could be early biomarkers to detect cognitive impairment in PD.


Asunto(s)
Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Hipocampo/patología , Enfermedad de Parkinson/complicaciones , Anciano , Anciano de 80 o más Años , Trastornos del Conocimiento/diagnóstico por imagen , Femenino , Lateralidad Funcional , Hipocampo/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Escala del Estado Mental , Persona de Mediana Edad , Pruebas Neuropsicológicas
6.
J Alzheimers Dis ; 49(4): 1169-77, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26599056

RESUMEN

BACKGROUND: Post stroke cognitive impairment (PSCI), an important complication of strokes, has numerous risk factors. A scale adequately classifying risk of cognitive impairment 3-6 months after mild stroke will be useful for clinicians. OBJECTIVE: To develop a risk score based on clinical and neuroimaging variables that will be useful in identifying mild ischemic stroke patients at high risk for PSCI. METHODS: The risk score development cohort comprised of a retrospective dataset of 209 mild stroke patients with MRI confirmed infarcts, without pre-stroke cognitive impairment, and evaluated within 6 months post-stroke for PSCI. Logistic regression identified factors predictive of PSCI and a risk score was developed based on regression coefficients. The risk score was checked for stability using 10-fold cross-validation and validated in an independent prospective cohort of 185 ischemic mild stroke patients. RESULTS: Within 6 months post-stroke, 37.32% developed PSCI in the retrospective dataset. A 15-point risk score based on age, education, acute cortical infarcts, white matter hyperintensity, chronic lacunes, global cortical atrophy, and intracranial large vessel stenosis was highly predictive of PSCI with an AUC of 0.829. 10.11% with low scores, 52.69% with moderate scores, and 74.07% with high scores developed PSCI. In the prospective validation cohort, the model had an AUC of 0.776, and exhibited similar accuracy and stability statistics at both 6 and 12 months. CONCLUSION: The seven item risk score adequately identified mild stroke patients who are at an increased risk of developing PSCI.


Asunto(s)
Isquemia Encefálica/complicaciones , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/etiología , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Anciano , Envejecimiento/patología , Área Bajo la Curva , Encéfalo/patología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/patología , Isquemia Encefálica/psicología , Trastornos del Conocimiento/patología , Constricción Patológica , Escolaridad , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/psicología , Sustancia Blanca/patología
7.
Parkinsonism Relat Disord ; 23: 50-6, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26711668

RESUMEN

BACKGROUND: Depression and anxiety are common in Parkinson's disease (PD) and contribute significantly to a reduced quality of life in PD patients. Though they often co-exist, it is unclear whether depression and anxiety result from a shared pathological process. We studied the longitudinal course and determinants of depression and anxiety in PD in order to understand which factors contribute to the development of these symptoms. METHODS: We conducted a prospective longitudinal study of 89 mild PD patients over 18 months, measuring depressive and anxiety symptoms at 6 monthly intervals using the Geriatric Depression Scale and Hospital Anxiety and Depression Scale--'Anxiety' subscale. Univariate and multivariate Generalised Estimating Equations were used to investigate the course of depression and anxiety and their association with demographic factors, motor measures, non-motor symptoms, and pharmacological factors. RESULTS: Depression and anxiety were co-morbid in 13.5% of the sample. Depressive symptoms remained relatively stable while anxiety symptoms improved over the course of 18 months. Severity of depressive symptoms was associated with female gender, motor fluctuations, apathy, and anxiety, while severity of anxiety was associated with older age, higher educational attainment, shorter disease duration, younger age of disease onset, and excessive daytime sleepiness. CONCLUSIONS: Although depression and anxiety are frequently co-morbid in PD, they were dissociable from each other. They had distinct trajectories and different longitudinal relationships with demographic, motor, and non-motor factors that were unique to each disorder.


Asunto(s)
Ansiedad , Depresión , Enfermedad de Parkinson/psicología , Anciano , Anciano de 80 o más Años , Ansiedad/epidemiología , Ansiedad/etiología , Comorbilidad , Depresión/epidemiología , Depresión/etiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/complicaciones , Estudios Prospectivos
8.
Parkinsonism Relat Disord ; 23: 95-8, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26705846

RESUMEN

INTRODUCTION: Apathy is one of the most common behavioural disorders in Parkinson's disease (PD) and contributes significantly to a reduced quality of life in PD patients. METHODS: We conducted a prospective longitudinal study of 89 mild PD patients over 18 months, measuring apathy symptoms at 6-monthly intervals using the Starkstein Apathy Scale, as well as measures of motor and non-motor symptoms, cognitive function, and functional disability at baseline. Mixed-effects models were used to characterise the individual trajectories of apathy symptom severity, and linear regression with stepwise elimination procedure was used to select significant baseline predictors. RESULTS: Clinically significant levels of apathy were present in 42.7% of our sample at baseline, with symptom severity remaining relatively stable on average over the course of 18 months. Male gender, lower educational attainment, higher depression symptom severity, more severe functional disability, and the presence of dyskinesias at study entry predicted increasing apathy over the subsequent 18 months. CONCLUSIONS: Patients with these factors are at risk for progression of apathy, which may be prevented by treating depression and functional disability. Further studies are needed to address both the specific neurobiological pathways and psychosocial factors underpinning apathy in PD.


Asunto(s)
Apatía , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/psicología , Anciano , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Calidad de Vida/psicología , Factores de Riesgo
9.
J Neurol Sci ; 371: 131-136, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27871434

RESUMEN

BACKGROUND: Anxiety is prevalent in patients with Parkinson's disease (PD) and may affect patients' quality of life. Yet, little is known about the neural basis of anxiety in PD, and none have used a longitudinal design. METHODS: 73 patients with mild PD were recruited and followed up for 18months. A whole-brain analysis was first used to identify brain regions associated with anxiety symptoms, followed by a regional analysis focusing on a priori hypothesised regions at baseline. A multivariate generalized estimating equations analysis was then conducted to determine the longitudinal association between grey matter (GM) volumetric changes of these significant regions and changes of anxiety symptoms. RESULTS: At baseline, anxiety symptom severity was associated with decreased GM volumes in the bilateral precuneus and anterior cingulate cortex (ACC). Over 18months, increased severity of anxiety symptoms was associated with decreased GM volume in the left precuneus and ACC, independent of age, gender, education, depressive symptom severity or use of psychiatric medication. CONCLUSIONS: These results mainly implicate the precuneus and ACC in the pathogenesis of anxiety in PD. We speculate that these structural changes could reflect the disrupted default mode network due to PD pathology, contributing to spontaneous anxiety-related self-focused thoughts.


Asunto(s)
Ansiedad/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/psicología , Anciano , Antiparkinsonianos/uso terapéutico , Ansiedad/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Sustancia Gris/diagnóstico por imagen , Humanos , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Tamaño de los Órganos , Enfermedad de Parkinson/tratamiento farmacológico , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Psicotrópicos/uso terapéutico , Índice de Severidad de la Enfermedad
10.
Parkinsonism Relat Disord ; 21(9): 1056-60, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26117438

RESUMEN

BACKGROUND: Studies have suggested a relationship between non-motor symptoms with motor fluctuations in patients with Parkinson's disease (PD). We studied the influence of depression on longitudinal motor and cognitive function among mild PD patients. METHODS: A 1.5 years longitudinal study of 102 patients with mild idiopathic PD. Patients were assessed with a standardized clinical assessment battery including motor and non-motor scales. Patients also underwent serial neurocognitive testing that assessed global cognition, memory, attention, language, visuospatial and executive function. RESULTS: 81 patients with mean age of 64.9(SD = 7.9) years and mean Hoehn & Yahr of 1.9(SD = 0.4) completed baseline and follow-up visits. 22 patients had clinically significant depression at baseline with mean Geriatric Depression Scale of 6.9(SD = 2.4). These patients presented with concomitant apathy and anxiety and were more likely to be females with longer duration of PD. At baseline, patients with depression had poorer performance on global cognition and all cognitive domains although not significantly different from patients without depression. At follow-up, there was no statistically significant difference on cognitive performance between those with and without baseline depression. Patients with baseline depression demonstrated worsening of motor function after 18 months (UPDRS Motor Score Change: +5.0[7.0]vs.+0.2[7.3]; p = 0.015). On multivariate analysis Baseline Motor Score (B = -0.229,CI = -0.445 to-0.013,p = 0.038), Baseline GDS (B = 0.622,CI = 0.078 to 1.166,p = 0.026) and PD duration (B = 0.520,CI = 0.105 to 0.935,p = 0.015) independently predicted increase in UPDRS Motor Score. CONCLUSIONS: The findings suggest a relationship between early depression with motor worsening and cognition decline in PD patients. Further biomarker-supported studies investigating the role of depression on motor and cognitive function are needed.


Asunto(s)
Trastornos del Conocimiento/etiología , Depresión/complicaciones , Depresión/etiología , Actividad Motora/fisiología , Enfermedad de Parkinson/complicaciones , Anciano , Atención , Función Ejecutiva , Femenino , Humanos , Modelos Lineales , Estudios Longitudinales , Masculino , Memoria , Persona de Mediana Edad , Pruebas Neuropsicológicas , Escalas de Valoración Psiquiátrica , Estadísticas no Paramétricas , Percepción Visual
11.
Clin Interv Aging ; 10: 771-80, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25945043

RESUMEN

BACKGROUND: Mild cognitive impairment (MCI) and dementia are reaching epidemic proportions in Asia. Lack of awareness and late presentation are major obstacles to early diagnosis and timely intervention. Cognitive screening may be an effective method for early detection of dementia in Asia. The purpose of this work was to study the characteristics of subjects volunteering for cognitive screening in an Asian setting and to determine the prevalence of MCI. METHODS: Retrospective and cross-sectional data from community subjects attending a screening program from 2008 to 2013 were analyzed. Information on demographics, vascular risk factors, subjective symptoms, and cognitive measures were analyzed over the 6-year period. RESULTS: Over the 6 years from 2008 to 2013, 1,243 community subjects voluntarily turned up for cognitive screening (91.2% were Chinese, 5.23% were Indian, 1.37% were Malay, and 2.25% were Eurasian). The mean age of the participants was 61.3 years and the mean number of years of education was 11.0 years. A total of 71.1% of participants were living in public housing, 59.8% had at least one cardiovascular risk factor, and 56.2% reported subjective cognitive symptoms. Over a period of 6 years, no significant change in demographic or clinical variables was noted. High cholesterol and hypertension were consistently the top two risk factors found in the population screened. In total, 17.2% of the total cohort had MCI. Across the 6 years, the proportion with MCI and depression was relatively constant. CONCLUSION: A significant proportion of participants attending voluntary cognitive screening have MCI. Low level of education and presence of vascular risk factors are general predisposing characteristics for MCI, and there are more specific factors pertaining to sex and employment status.


Asunto(s)
Disfunción Cognitiva/diagnóstico , Anciano , Pueblo Asiatico , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Demencia/diagnóstico , Femenino , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Retrospectivos , Factores de Riesgo , Factores Socioeconómicos , Población Urbana
12.
Parkinsonism Relat Disord ; 21(5): 483-8, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25753847

RESUMEN

INTRODUCTION: Existing literature on brain volumetric alterations in patients with Parkinson's disease (PD) have mainly focused on gray matter (GM) and are largely cross-sectional. Little is known about white matter (WM) volumetric features and their impact on cognitive symptoms in PD. Therefore, the present study aims to examine both GM and WM volumes of cognitively asymptomatic PD patients with a longitudinal design. METHODS: A total of 42 cognitively asymptomatic patients with early stage PD were recruited and followed up for 1.5 years. At follow-up, 12 patients progressed to mild cognitive impairment (MCI) and were classified as "converters" while the remaining 30 patients remained cognitively asymptomatic and were classified as "non-converters". All patients underwent clinical and neuropsychological assessments as well as MRI scans at baseline and at follow-up. RESULTS: At baseline, non-converters and converters had comparable cognitive scores. At follow-up, converters showed more deficits in frontal-related cognitive function than non-converters. Volumetric analyses revealed that converters had more longitudinal reduction in WM, but not GM, volume compared to non-converters. The decreased volumes among converters were mainly localized in the frontal areas. Moreover, baseline global WM volume significantly predicted conversion to PD-MCI, while baseline GM and WM volumes of the frontal and parietal regions were associated with frontal cognitive changes across time. CONCLUSION: PD patients who develop MCI demonstrate longitudinal reduction in WM volume, especially in the frontal areas. While both regional GM and WM volumes associate with frontal cognitive decline, baseline global WM volume may be a neuroimaging marker of conversion to PD-MCI.


Asunto(s)
Encéfalo/patología , Cognición , Disfunción Cognitiva/diagnóstico , Progresión de la Enfermedad , Enfermedad de Parkinson/diagnóstico , Anciano , Cognición/fisiología , Disfunción Cognitiva/psicología , Estudios Transversales , Femenino , Estudios de Seguimiento , Sustancia Gris/patología , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Enfermedad de Parkinson/psicología , Valor Predictivo de las Pruebas , Sustancia Blanca/patología
13.
Oncotarget ; 6(26): 22098-113, 2015 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-26061747

RESUMEN

Epithelial-mesenchymal transition (EMT), a crucial mechanism in carcinoma progression, describes the process whereby epithelial cells lose their apico-basal polarity and junctional complexes and acquire a mesenchymal-like morphology. Several markers are considered to be authentic indicators of an epithelial or mesenchymal status; however, there is currently no comprehensive or systematic method with which to determine their functional relevance. Previously, we identified a 33-gene EMT signature comprising 25 epithelial and 6 mesenchymal genes that best describe this concept of the EMT spectrum. Here, we designed small-scale siRNA screens targeting these six mesenchymal signature genes (CD99L2, EMP3, ITGA5, SYDE1, VIM, ZEB1) to explore their functional relevance and their roles during EMT reversal by nintedanib (BIBF1120) in a mesenchymal-like SKOV3 ovarian cancer cell line. We found that neither cell proliferation nor cytotoxicity was affected by silencing any of these genes. SKOV3 cells expressing siRNA against mesenchymal genes (ZEB1, EMP3, CD99L2, ITGA5, and SYDE1) showed enhanced colony compaction (reduced inter-nuclear distance). Inductions of E-cadherin expression were only observed in SYDE1- and ZEB1-silenced SKOV3 cells. In addition, only SYDE1-silenced SKOV3 cells showed increased anoikis. Finally, we identified that SYDE1 and ZEB1 were down-regulated in nintedanib-treated SKOV3 cells and SYDE1- and ZEB1-silenced SKOV3 cells showed enhanced nintedanib-induced up-regulation of E-cadherin. Nintedanib-treated SKOV3 cells also showed colony compaction and decreases in EMT scores both in vitro and in vivo. We conclude that SYDE1 and ZEB1 are functionally relevant in EMT reversal. This study thus provides a proof-of-concept for the use of in vitro siRNA screening to explore the EMT-related functions of selected genes and their potential relevance in the discovery of EMT reversing drugs.


Asunto(s)
Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Indoles/farmacología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Resultado del Tratamiento
14.
Drugs R D ; 14(3): 195-203, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25063270

RESUMEN

BACKGROUND: Evidence is lacking for cognitive enhancer therapy in patients with Alzheimer's disease (AD) and concomitant cerebrovascular disease (mixed AD) as such patients would have been excluded from clinical trials. Earlier studies of mixed AD have focused on large vessel cerebrovascular disease. The influence of small vessel cerebrovascular disease (svCVD) in the form of white matter hyperintensity (WMH) on treatment outcomes in mixed AD has not been addressed. OBJECTIVE: In this long-term naturalistic study, we evaluated the effectiveness of cognitive enhancers in patients with mixed AD with svCVD. METHODS: We conducted a retrospective analysis of a prospective clinical database from a memory clinic of a tertiary hospital. Magnetic resonance imaging WMH was used as a marker of svCVD. Demographic, cognitive, and treatment data were analysed. Linear mixed models with patient-specific random effects were used to evaluate cognitive outcomes over time while adjusting for confounders. RESULTS: Patients with mixed AD (n = 137) or AD without svCVD (pure AD) (n = 28) were studied over a median duration of 28.7 months. Patients with mixed AD had a higher prevalence of hypertension (62.8 vs. 35.7 %, p = 0.011). The majority (75.2 %) of the study sample were managed with monotherapy. Mini Mental State Examination (MMSE) scores decreased over time (-0.04, p = 0.007), and the decrease was similar for both diagnosis groups (-0.03, p = 0.246). Annual estimated mean MMSE decline was 0.84 for pure AD and 0.48 for mixed AD. Similar trends were observed with Montreal Cognitive Assessment (MoCA) scores, with annual estimated mean reduction of 0.72 and 0.48 for pure AD and mixed AD, respectively. CONCLUSION: Cognitive enhancers are effective in slowing the rate of cognitive decline in patients with AD with svCVD. These findings would need to be confirmed in randomized clinical trials.


Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Trastornos Cerebrovasculares/tratamiento farmacológico , Trastornos del Conocimiento/tratamiento farmacológico , Nootrópicos/farmacología , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/fisiopatología , Trastornos Cerebrovasculares/etiología , Trastornos del Conocimiento/etiología , Bases de Datos Factuales , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Sustancia Blanca/patología
15.
Parkinsonism Relat Disord ; 20(11): 1203-8, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25258331

RESUMEN

BACKGROUND: Longitudinal neuroimaging studies could provide insights into pathophysiology of cognitive impairment in PD. We examined the role of hippocampal atrophy and cerebral white matter disease as risk factors for mild cognitive impairment and dementia in PD. METHODS: Prospective longitudinal study of patients with mild PD in a tertiary neurology center. All subjects underwent baseline MRI brain and had baseline and 6 monthly cognitive evaluations. Cognitive impairment was diagnosed based on the Movement Disorder Society Criteria. The predictive role of hippocampal volume and white matter hyperintensity at baseline on progression of cognitive impairment was studied. RESULTS: 97 subjects with mean age 65.3 years, mean education of 10.3 years and mean Hoehn & Yahr of 1.9 were studied. Over 2 years, 16 subjects developed mild cognitive impairment and 8 subjects with mild cognitive impairment progressed to dementia. After adjusting for age and vascular risk factors, hippocampal volume was a significant predictor for mild cognitive impairment (OR 7.05, CI 1.5-34.1; p = 0.015) and dementia (OR 7.03, CI 2.39-25.2; p = 0.001). With Cox regression, hippocampal volume was a significant predictor for "time to cognitive impairment" (HR 7.67; CI 3.47-16.95, p < 0.001). Difference between survival curves based on volume of white matter hyperintensity in predicting "time to mild cognitive impairment" was significant (p = 0.0295). CONCLUSIONS: Hippocampal volume is a major factor predicting the development of mild cognitive impairment and dementia in PD. White matter hyperintensity also contributes to the longitudinal cognitive status in PD.


Asunto(s)
Demencia/diagnóstico , Demencia/etiología , Hipocampo/patología , Leucoencefalopatías/etiología , Enfermedad de Parkinson/complicaciones , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Estudios Longitudinales , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , Índice de Severidad de la Enfermedad
16.
PLoS One ; 7(4): e34663, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22493708

RESUMEN

INTRODUCTION: Since 2008, the Singapore Ministry of Health (MOH) has expanded HIV testing by increasing anonymous HIV test sites, as well as issuing a directive to hospitals to offer routine voluntary opt out inpatient HIV testing. We reviewed this program implemented at the end of 2008 at Tan Tock Seng Hospital (TTSH), the second largest acute care general hospital in Singapore. METHODS AND FINDINGS: From January 2009 to December 2010, all inpatients aged greater or equal than 21 years were screened for HIV unless they declined or were not eligible for screening. We reviewed the implementation of the Opt Out testing policy. There were a total of 93,211 admissions; 41,543 patients were included based on HIV screening program eligibility criteria. Among those included, 79% (n = 32,675) opted out of HIV screening. The overall acceptance rate was 21%. Majority of eligible patients who were tested (63%) were men. The mean age of tested patients was 52 years. The opt out rate was significantly higher among females (OR: 1.5, 95%CI: 1.4-1.6), aged >60 years (OR: 2.3, 95%CI: 2.2-2.4) and Chinese ethnicity (OR: 1.7, 95%CI:1.6-1.8). The false positive rate of the HIV screening test is 0.56%. The proportion of patients with HIV infection among those who underwent HIV screening is 0.18%. All 16 confirmed HIV patients were linked to care. CONCLUSION: The default opt-in rate of inpatient HIV testing was low at Tan Tock Seng Hospital, Singapore. Efforts to address individual HIV risk perception and campaigns against HIV stigma are needed to encourage more individuals to be tested for HIV.


Asunto(s)
Pruebas Anónimas/psicología , Infecciones por VIH/diagnóstico , Seropositividad para VIH/diagnóstico , Aceptación de la Atención de Salud/psicología , Adulto , Pruebas Anónimas/estadística & datos numéricos , Servicio de Urgencia en Hospital , Femenino , VIH/genética , Infecciones por VIH/virología , Seropositividad para VIH/virología , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/estadística & datos numéricos , Factores Sexuales , Singapur
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