RESUMEN
The dysregulation of developmental and stem cell-associated genes is a common phenomenon during cancer development. Around half of patients with acute myeloid leukemia (AML) express high levels of HOXA cluster genes and MEIS1. Most of these AML cases harbor an NPM1 mutation (NPM1c), which encodes for an oncoprotein mislocalized from the nucleolus to the cytoplasm. How NPM1c expression in hematopoietic cells leads to its characteristic gene-expression pattern remains unclear. Here, we show that NPM1c directly binds to specific chromatin targets, which are co-occupied by the histone methyltransferase KMT2A (MLL1). Targeted degradation of NPM1c leads to a rapid decrease in gene expression and loss of RNA polymerase II, as well as activating histone modifications at its targets. We demonstrate that NPM1c directly regulates oncogenic gene expression in collaboration with the MLL1 complex and define the mechanism by which MLL1-Menin small-molecule inhibitors produce clinical responses in patients with NPM1-mutated AML. SIGNIFICANCE: We uncovered an important functional role of mutant NPM1 as a crucial direct driver of oncogenic gene expression in AML. NPM1c can bind to chromatin and cooperate with the MLL complex, providing the first functional insight into the mechanism of Menin-MLL inhibition in NPM1c leukemias. See related article by Wang et al., p. 724. This article is highlighted in the In This Issue feature, p. 517.
Asunto(s)
Leucemia Mieloide Aguda , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleofosmina , Mutación , Leucemia Mieloide Aguda/patología , Cromatina/genéticaRESUMEN
Translocations involving the NUP98 gene produce NUP98-fusion proteins and are associated with a poor prognosis in acute myeloid leukemia (AML). MLL1 is a molecular dependency in NUP98-fusion leukemia, and therefore we investigated the efficacy of therapeutic blockade of the menin-MLL1 interaction in NUP98-fusion leukemia models. Using mouse leukemia cell lines driven by NUP98-HOXA9 and NUP98-JARID1A fusion oncoproteins, we demonstrate that NUP98-fusion-driven leukemia is sensitive to the menin-MLL1 inhibitor VTP50469, with an IC50 similar to what we have previously reported for MLL-rearranged and NPM1c leukemia cells. Menin-MLL1 inhibition upregulates markers of differentiation such as CD11b and downregulates expression of proleukemogenic transcription factors such as Meis1 in NUP98-fusion-transformed leukemia cells. We demonstrate that MLL1 and the NUP98 fusion protein itself are evicted from chromatin at a critical set of genes that are essential for the maintenance of the malignant phenotype. In addition to these in vitro studies, we established patient-derived xenograft (PDX) models of NUP98-fusion-driven AML to test the in vivo efficacy of menin-MLL1 inhibition. Treatment with VTP50469 significantly prolongs survival of mice engrafted with NUP98-NSD1 and NUP98-JARID1A leukemias. Gene expression analysis revealed that menin-MLL1 inhibition simultaneously suppresses a proleukemogenic gene expression program, including downregulation of the HOXa cluster, and upregulates tissue-specific markers of differentiation. These preclinical results suggest that menin-MLL1 inhibition may represent a rational, targeted therapy for patients with NUP98-rearranged leukemias.
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N-Metiltransferasa de Histona-Lisina/metabolismo , Leucemia Mieloide Aguda/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Proteínas de Complejo Poro Nuclear/genética , Proteínas Proto-Oncogénicas/metabolismo , Animales , Línea Celular Tumoral , Regulación Leucémica de la Expresión Génica , Reordenamiento Génico , N-Metiltransferasa de Histona-Lisina/genética , Leucemia Mieloide Aguda/metabolismo , Ratones , Ratones Endogámicos C57BL , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Complejo Poro Nuclear/metabolismo , Proteínas de Fusión Oncogénica/genética , Proteínas de Fusión Oncogénica/metabolismo , Mapas de Interacción de Proteínas , Proteínas Proto-Oncogénicas/genéticaRESUMEN
The initiating mutations that contribute to cancer development are sometimes present in premalignant cells. Whether therapies targeting these mutations can eradicate premalignant cells is unclear. Acute myeloid leukemia (AML) is an attractive system for investigating the effect of preventative treatment because this disease is often preceded by a premalignant state (clonal hematopoiesis or myelodysplastic syndrome). In Npm1c/Dnmt3a mutant knock-in mice, a model of AML development, leukemia is preceded by a period of extended myeloid progenitor cell proliferation and self-renewal. We found that this self-renewal can be reversed by oral administration of a small molecule (VTP-50469) that targets the MLL1-Menin chromatin complex. These preclinical results support the hypothesis that individuals at high risk of developing AML might benefit from targeted epigenetic therapy in a preventative setting.
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Terapia Genética/métodos , Leucemia Experimental/prevención & control , Leucemia Mieloide Aguda/prevención & control , Proteínas Nucleares/genética , Preleucemia/terapia , Animales , Cromatina/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genética , ADN Metiltransferasa 3A , Técnicas de Sustitución del Gen , N-Metiltransferasa de Histona-Lisina/metabolismo , Leucemia Experimental/genética , Leucemia Mieloide Aguda/genética , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Mutación , Células Progenitoras Mieloides/patología , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Nucleofosmina , Preleucemia/genética , Preleucemia/patología , Proteínas Proto-Oncogénicas/metabolismoRESUMEN
OBJECTIVE: The psychometric properties of the Chinese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module were investigated. METHODS: This instrument and the Generic Core Scales were administered to 359 pediatric patients with cancer (5-18 years) and 413 parents of such patients (2-18 years old). RESULTS: Seven and eight factors were, respectively, identified for the patient and parent versions. The Cronbach's alpha coefficients were respectively .89 and .92 for the total scale, and respectively .75-.90 and .76-.93 for the subscales of the patient and parent versions. Test-retest reliability coefficients exceeded .60 for most cases. The total/subscale scores of the Cancer Module significantly correlated with those of the Generic Core Scales. Some of the subscales could distinguish between on-treatment and off-treatment patients. CONCLUSIONS: The psychometric properties of the patient and parent versions of the Chinese PedsQL Cancer Module were found acceptable.
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Estado de Salud , Neoplasias/psicología , Calidad de Vida/psicología , Encuestas y Cuestionarios/normas , Actividades Cotidianas , Adolescente , Niño , Preescolar , Femenino , Hong Kong , Humanos , Masculino , Padres , Psicometría , Reproducibilidad de los Resultados , Apoyo SocialRESUMEN
The purpose of this study was to translate the Memorial Symptom Assessment Scale (MSAS) into Chinese and evaluate the psychometric properties of this version. The original MSAS is a 32-item, patient-rated measure that was developed to assess common cancer-related physical and psychological symptoms with respect to frequency, intensity, and distress. In this study, a two-phase design was used. Phase I involved iterative forward-backward translation, testing of content validity (CVI) and a pretest. Phase II established the psychometric properties of the Chinese version MSAS (MSAS-Ch). Results showed that the MSAS-Ch achieved content relevancy CVI of 0.94 and semantic equivalence CVI of 0.94. Pretesting was performed in 10 cancer patients, and the results revealed adequate content coverage and comprehensibility of the MSAS-Ch. A convenience sample of 370 patients undergoing cancer therapy or at the early post-treatment stage was recruited for psychometric evaluation. Confirmatory factor analysis confirmed the construct validity of the MSAS-Ch, with a good fit between the factor structure of the original version and our present sample data (goodness-of-fit indices all above 0.95). The internal consistency reliability of subscales and total MSAS-Ch was moderately high, with Cronbach alpha coefficients ranging from 0.79 to 0.87. The test-retest intraclass correlation results for the subscale and total MSAS-Ch ranged from 0.68 to 0.79. The subscale scores of MSAS-Ch were moderately correlated with the scores on various validation measurements that assessed psychological distress, pain, and health-related quality of life (r = 0.46-0.65, P < 0.01), confirming that they were measurements of similar constructs. The validity of the construct validity was also supported by comparing the MSAS-Ch scores for subpopulations that varied clinically. Inpatients and patients with poorer performance status scored higher on the MSAS-Ch subscale and total scores than outpatients and patients with higher performance status (P < 0.05). Our study shows that the MSAS-Ch has adequate psychometric properties of validity and reliability, and can be used to assess symptoms during cancer therapy and at the early post-treatment stage in Chinese-speaking patients.
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Indicadores de Salud , Neoplasias/diagnóstico , Neoplasias/epidemiología , Dolor/diagnóstico , Dolor/epidemiología , Calidad de Vida , Índice de Severidad de la Enfermedad , Ansiedad/diagnóstico , Ansiedad/epidemiología , China/epidemiología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Large population growth surveys of children and adolescents aged 6 to 18 y were undertaken in Hong Kong in 1963 and 1993. The global epidemic of obesity is a major public health concern. To monitor the impact of this epidemic in Hong Kong children and to identify secular changes in growth, a further growth survey was undertaken in 2005/6. METHODS: Cross-sectional height and weight measurements of 14,842 children and adolescents aged 6 to 18 y from Hong Kong's 18 districts were obtained during the 2005/6 school year. Percentile curves were constructed using LMS method and sex-specific percentile values of weight-for-age, height-for-age, and BMI-for-age were compared with those data from 1963 and 1993. RESULTS: Secular changes in height, weight and BMI were noted between 1963 and 1993 and between 1993 and 2005/6. In the latter period, greater changes were observed at younger ages, and particularly in boys. On an annual basis, the 1993-2005/6 changes were less than those during 1963-1993. Using the International Obesity Task Force cut-offs, 16.7% of children were overweight or obese in 2005/6, which was a 5.1% increase since 1993. CONCLUSION: These data provide policy-makers with further evidence of the secular changes in child growth and the increasing obesity epidemic among Hong Kong children.
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Estatura , Índice de Masa Corporal , Peso Corporal , Adolescente , Niño , Estudios Transversales , Femenino , Hong Kong , Humanos , MasculinoRESUMEN
OBJECTIVE: The purpose of our study was to determine the prevalence, pattern, and spectrum of glenoid bone loss in anterior shoulder dislocation, to relate this to the frequency of dislocation, and to test the appropriateness of the measurement method. SUBJECTS AND METHODS: Two hundred eighteen patients with single or recurrent anterior shoulder dislocation underwent shoulder CT examination. Fifteen patients had bilateral dislocation. Prevalence and severity of glenoid bone loss and glenoid fracture were assessed. CT examinations of 56 control subjects without shoulder dislocation were evaluated for glenoid contour and side-to-side variation in glenoid width. RESULTS: Glenoid bone loss was present in 27 (41%) of 66 patients with first-time unilateral dislocation and 118 (86%) of 137 patients with recurrent unilateral dislocation. Glenoid bone loss ranged from -0.3% to -33% (mean, -10.8% +/- 7.9%). Seventy-four (51%) of 145 patients had < or = 10% glenoid bone loss, 54 (37%) had between 10% and 20%, eight (6%) had between 20% and 25% glenoid bone loss, and nine (6%) had > or = 25% glenoid bone loss. Glenoid rim fractures were present in 49 (21%) of 233 dislocated shoulders. The number of dislocations correlated moderately with the severity of glenoid bone loss (r = 0.56). The normal side-to-side glenoid width variation was small (0.46 +/- 0.81 mm). CONCLUSION: Glenoid bone loss is common in anterior shoulder dislocation. It is probably multifactorial in origin, is usually mild in degree, and has a maximum observed severity of -33%. Dislocation frequency cannot accurately predict the degree of bone loss.
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Resorción Ósea/diagnóstico por imagen , Resorción Ósea/epidemiología , Escápula , Luxación del Hombro/diagnóstico por imagen , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Reproducibilidad de los Resultados , Factores de Riesgo , Índice de Severidad de la Enfermedad , Luxación del Hombro/complicaciones , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate the longitudinal changes in the disability level of elders with LBP after receiving auriculotherapy. DESIGN: Randomized controlled trial. SETTINGS: Sixty participants who were 60 years old or above and who were suffering from LBP were recruited from five hostels for the elders in Hong Kong. INTERVENTIONS: The participants were randomly allocated to receive a 3-week session of auriculotherapy using either semen vaccariae (control group=30) or magnetic pellets (experimental group=30). Seven auricular acupoints that are expected to have an effect on LBP were selected. MAIN OUTCOME MEASURES: Assessment data were collected at five points of time: (i) baseline, (ii) about 1.5 weeks of treatment, (iii) 3 weeks of treatment, (iv) 2 weeks post-treatment, and (v) 4 weeks post-treatment using the modified Aberdeen low back pain disability scale (Chinese). RESULTS: When the rate of change was compared between the two groups at each point of time starting from the baseline, those in the experimental group demonstrated significant improvement in the overall disability level, pain/sensation, and physical and functional abilities at 1.5 weeks of treatment (p<0.001), 3 weeks of treatment (p<0.001), 2 weeks post-treatment (p<0.001), and 4 weeks post-treatment (p<0.001). CONCLUSION: Longitudinal changes in the improvement of disability level were found among the elders with low back pain after receiving auriculotherapy using magnetic pellets.
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Acupuntura Auricular/métodos , Dolor de la Región Lumbar/terapia , Anciano de 80 o más Años , Evaluación de la Discapacidad , Femenino , Humanos , Estudios Longitudinales , Dolor de la Región Lumbar/fisiopatología , Magnetismo , Masculino , Semillas , VaccariaRESUMEN
BACKGROUND AND PURPOSE: Stroke, a major health issue affecting the elderly, limits their participation in society. The aim of this study was to investigate changes in stroke survivors' handicap levels and to identify their determinants in the subacute phase from 3 months to 1 year. METHODS: Data were collected from a prospective cohort of 303 Chinese stroke survivors with the use of questionnaires, including the Lawton Instrumental Activities of Daily Living-Chinese Version (IADL-CV), Barthel Index, Chinese Mini-Mental State Examination, Chinese Geriatric Depression Scale, and the Chinese version of the London Handicap Scale. RESULTS: A total of 297 and 268 patients were successfully followed up at 6 and 12 months, respectively. Whereas IADL remained unchanged throughout, we found an improvement in Barthel Index but a deterioration in the Chinese Geriatric Depression Scale score at 12 months. Multilevel modeling revealed improvements in the mobility and social integration handicap domains and a deterioration in the orientation domain at 12 months. Overall handicap remained unchanged. At 12 months, depression was most significantly and independently associated with poststroke handicap, and advanced old age alone (>80 years) was associated with clinically significant deterioration in handicap. CONCLUSIONS: Even though IADL remained static at 1 year, mobility and social integration handicap dimensions can be improved in the early community phase after stroke. Nonphysical factors such as depression were confirmed to be significantly associated with handicap. Rehabilitation should target the high-risk group of very elderly stroke survivors who were 4 times more likely to deteriorate in handicap.
Asunto(s)
Evaluación de la Discapacidad , Personas con Discapacidad/psicología , Accidente Cerebrovascular/fisiopatología , Accidente Cerebrovascular/psicología , Actividades Cotidianas/psicología , Anciano , Anciano de 80 o más Años , China , Estudios de Cohortes , Depresión/fisiopatología , Depresión/psicología , Personas con Discapacidad/clasificación , Femenino , Estudios de Seguimiento , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Limitación de la Movilidad , Análisis Multivariante , Estudios Prospectivos , Rehabilitación de Accidente CerebrovascularRESUMEN
BACKGROUND: A complex inflammatory response associated with the use of cardiopulmonary bypass may ultimately lead to organ dysfunction. We investigate the effect of continuing ventilation during cardiopulmonary bypass on inflammatory reactions and cardiopulmonary function. METHODS: Fifty patients undergoing cardiopulmonary bypass were prospectively randomized to continuous ventilation and nonventilation groups. Plasma interleukin-8, interleukin-10, matrix metalloproteinase-9, tissue inhibitor metalloproteinase-1, and thromboxane B2 levels were measured preoperatively, at 1, 4, and 6 hours after aortic declamping. Levels of these mediators were also determined in bronchoalveolar lavage preoperatively and four hours after declamping. Seven parameters of cardiopulmonary function, including dynamic compliance and systemic vascular resistance, were recorded during the same time points. RESULTS: Plasma interleukin-10 levels were higher at 6 hours and tissue inhibitor metalloproteinase-1 levels were higher at 1 hour after aortic declamping in the continuous ventilation compared with the nonventilation group (p = 0.04 and 0.002, respectively), while bronchoalveolar lavage levels of tissue inhibitor metalloproteinase-1 were also higher in the continuous ventilation group 4 hours after declamping (p = 0.02). Plasma interleukin-8 levels were higher at 4 hours after declamping in the nonventilation group (p = 0.04). Postoperative dynamic compliance was better preserved in continuous ventilation patients than nonventilation patients at 6 hours after declamping (p = 0.0008). CONCLUSIONS: Continued ventilation during cardiopulmonary bypass results in lesser inflammatory and proteolytic responses, and may better preserve pulmonary function than cardiopulmonary bypass without ventilation.
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Puente Cardiopulmonar/métodos , Estenosis Coronaria/cirugía , Citocinas/sangre , Cuidados Intraoperatorios/métodos , Respiración Artificial/métodos , Puente Cardiopulmonar/efectos adversos , Angiografía Coronaria , Puente de Arteria Coronaria/métodos , Puente de Arteria Coronaria/mortalidad , Estenosis Coronaria/sangre , Estenosis Coronaria/diagnóstico por imagen , Estenosis Coronaria/mortalidad , Femenino , Estudios de Seguimiento , Pruebas de Función Cardíaca , Hemodinámica/fisiología , Humanos , Mediadores de Inflamación/sangre , Masculino , Monitoreo Intraoperatorio/métodos , Análisis Multivariante , Oxígeno/uso terapéutico , Probabilidad , Estudios Prospectivos , Valores de Referencia , Pruebas de Función Respiratoria , Medición de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
This study was designed to examine newborn infants in Hong Kong prenatally exposed to levels of methylmercury considered to increase risk of neurotoxic effects and to examine subject characteristics that modify the degree of prenatal mercury exposure. Mercury concentrations in 1057 sets of maternal and cord blood samples and 96 randomly selected maternal hair samples were measured. Subject characteristics were measured or collected by questionnaire. Of the 1057 cord blood samples collected only 21.6% had mercury concentrations less than 29 nmol/L (5.8 micro g/L). Median maternal hair mercury concentration was 1.7 ppm. The geometric mean cord to maternal blood mercury ratio was 1.79 to 1. Increasing maternal fish consumption and maternal age were found to be associated with increased cord blood mercury concentrations. Marine fish consumption increased cord blood mercury concentrations more than freshwater fish (5.09%/kg vs 2.86%/kg). Female babies, maternal alcohol consumption and increasing maternal height were associated with decreased cord blood mercury concentrations. Pregnant women in Hong Kong consume large amounts of fish and as a result, most of their offspring have been prenatally exposed to moderately high levels of mercury. In this population, pregnant women should choose freshwater over marine fish and limit fish consumption.
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Sangre Fetal/química , Exposición Materna , Intercambio Materno-Fetal , Mercurio/sangre , Compuestos de Metilmercurio , Animales , Femenino , Peces , Contaminación de Alimentos , Hong Kong , Humanos , Recién Nacido , Masculino , Compuestos de Metilmercurio/toxicidad , Embarazo , Distribución Aleatoria , Contaminantes Químicos del Agua/toxicidadRESUMEN
AIM: To assess the psychometric properties of the Chinese version of the Satisfaction with the Nursing Home Instrument. BACKGROUND: Resident's satisfaction has been regarded by the literature as a gold standard for quality of nursing home care. Accurate assessment of resident's satisfaction can provide valuable information for implementation of quality nursing home care. However, there is not a validated Chinese tool to serve the purpose. DESIGN: A cross-sectional descriptive survey design. METHODS: Content validity of the Chinese version of the Satisfaction with the Nursing Home Instrument was assessed by the use of expert panel. Construct validity of the Chinese version of the Satisfaction with the Nursing Home Instrument was determined by assessing the correlation between satisfaction with other theoretically related constructs. Internal consistency and stability of the Chinese version of the Satisfaction with the Nursing Home Instrument were determined by Cronbach's method and two-week test-retest reliability. The six-factor structure of the Chinese version of the Satisfaction with the Nursing Home Instrument was assessed by confirmatory factor analysis. Testing was performed on a cluster sample of 330 residents from 16 nursing homes in Hong Kong. RESULTS: The Chinese version of the Satisfaction with the Nursing Home Instrument demonstrated good content validity by having content validity index of 0.93. High construct validity of the Chinese version of the Satisfaction with the Nursing Home Instrument was supported by its significant correlation with depression (r = -0.42, P = 0.000), health-related quality of life (physical component) (r = 0.16, P = 0.042), health-related quality of life (mental component) (r = 0.41, P = 0.000) and global quality of care (r = 0.49, P = 0.000). The Chinese version of the Satisfaction with the Nursing Home Instrument demonstrated satisfactory internal consistency and good stability by having Cronbach's alpha of 0.79 and intra-class correlation coefficient of 0.94, respectively. The six-factor structure of the Chinese version of the Satisfaction with the Nursing Home Instrument was not fully supported by confirmatory factor analysis. CONCLUSIONS: The Chinese version of the Satisfaction with the Nursing Home Instrument is a useful instrument for assessing satisfaction of cognitively intact Chinese nursing home residents. Findings provided initial evidence on its validity and reliability. Further empirical testing is recommended to explore its factor structure. RELEVANCE TO CLINICAL PRACTICE: The Chinese version of the Satisfaction with the Nursing Home Instrument can provide guidance to enhance delivery of high-quality nursing home care for the Chinese population.
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Hogares para Ancianos , Casas de Salud , Satisfacción del Paciente , Encuestas y Cuestionarios , Anciano , Anciano de 80 o más Años , Estudios Transversales , Análisis Factorial , Femenino , Hong Kong , Humanos , Masculino , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: In adults, obstructive sleep apnea (OSA) is associated with insulin resistance and dyslipidemia. We aimed to establish correlation between OSA, serum lipid profile, and insulin levels in obese snoring children. METHODS: Consecutive obese children with habitual snoring were recruited. They underwent physical examination, overnight polysomnography (PSG), and metabolic studies. OSA was diagnosed if apnea hypopnea index (AHI) > 1.0, and cases were considered to have moderate to severe OSA if AHI > 10. RESULTS: Ninety-four obese subjects with habitual snoring were studied. Seventy-three subjects were male and the median age of the studied group was 12.0 years (IQR 9.7-13.9). None of the subjects had active cardiopulmonary disease, and the BMI values of our subjects were >95th percentile using local reference charts. Sixty subjects had OSA, 47 being mild, and 13 being moderate to severe OSA. Multiple logistic regression analysis revealed that saturation nadir and insulin levels were significantly associated with OSA. CONCLUSION: OSA is prevalent among obese children with habitual snoring and insulin is independently associated with the condition. Its role in the cardiovascular complications of childhood sleep apnea is worthy of further exploration.
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Pueblo Asiatico , Resistencia a la Insulina , Insulina/sangre , Obesidad/complicaciones , Apnea Obstructiva del Sueño/sangre , Adolescente , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Niño , Femenino , Hong Kong/epidemiología , Humanos , Técnicas para Inmunoenzimas , Masculino , Obesidad/sangre , Obesidad/etnología , Polisomnografía , Prevalencia , Pronóstico , Estudios Retrospectivos , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/etnologíaRESUMEN
OBJECTIVE: This study aimed to evaluate the parental suspicion of hearing loss in children with otitis media with effusion (OME). As part of a population-based survey in a screening programme among 6- to 7-year-old Chinese children in Hong Kong, OME cases and controls were studied for the value of parental observations in the prediction of OME and hearing test results. SUBJECTS AND METHODS: Prior to the otoscopic and tympanometric examination of the children on school premises, a self-administered binary-choice question was sent to the parents asking whether there was any suspicion of hearing impairment. Positive screens and randomly selected negative screens were seen in a hospital clinic for the confirmation of case and control status 2 to 3 weeks after the school screening. Aural examination under microscopy, repeated tympanometry and stapedial reflex testing, and pure-tone audiometry (PTA) were conducted, and 117 cases and 159 controls were included in this study. RESULTS: The average PTA conductive threshold levels in the individual children with OME ranged from 3.8 dB to 40.0 dB with a group mean of 17.0 dB in the better-hearing ears. Parental suspicion of hearing deficit was significantly associated with OME (p<0.001) but not PTA findings (p=0.686). The sensitivity of parent-suspected hearing impairment to detect OME however was very low (19.7%). DISCUSSION: In other words, if we had relied on parental suspicion as the first screening, at least 80% of the OME cases would have been missed. We conclude that the parental suspicion of hearing loss is inadequate for the identification of mild hearing loss as caused by OME. Health education is recommended to improve parental awareness of the disease.
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Pérdida Auditiva Conductiva/diagnóstico , Otitis Media con Derrame/diagnóstico , Padres , Umbral Auditivo , Estudios de Casos y Controles , Niño , Femenino , Pérdida Auditiva Conductiva/etiología , Pruebas Auditivas , Hong Kong , Humanos , Masculino , Otitis Media con Derrame/complicaciones , Otoscopía , Valor Predictivo de las Pruebas , Estudios Prospectivos , Sensibilidad y Especificidad , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To identify the risk factors for otitis media with effusion (OME) in Chinese schoolchildren and analyse the results with reference to the review of the literature. METHODS: The study subjects were 6-7-year-old children drawn from a school-screening program for OME in Hong Kong. Both positive and negative screens attended a hospital clinic for further assessment with repeated otoscopic examination and tympanometry as well as pure tone audiometry within 3 weeks after the initial school-screening. During the visit, parents were interviewed to provide information with regard to the children's birth history, neonatal history, socio-economic background, otological history, past health, and medical history. These data formed the basis in the estimation of potential risk factors for OME. RESULTS: In the univariate analysis of 127 cases and 173 controls, significantly elevated odds ratios (OR) for OME were detected on the symptoms of atopy (OR = 2.21, p = 0.04), hearing loss (OR = 4.13, p = 0.001), nasal obstruction (OR = 1.94, p = 0.005), rhinorrhoea (OR = 1.61, p = 0.04), tonsillitis in the past 12 months (OR = 1.82, p = 0.02), and previous history of acute otitis media (OR = 6.89, p < 0.001). However, only three of them were found to be significant in the multivariate logistic regression model: nasal obstruction (OR = 1.67, 95% CI: 1.01-2.75); acute tonsillitis (OR = 1.68, 95% CI: 1.00-2.80), and previous acute otitis media episodes (OR = 5.75, 95% CI: 2.60-12.69). CONCLUSIONS: Risk factors identified in the Chinese schoolchildren for OME were comparable with previous western reports. A previous attack of acute otitis media was a major determinant for middle ear effusion.
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Otitis Media con Derrame/epidemiología , Estudios de Casos y Controles , Niño , Femenino , Pérdida Auditiva/etiología , Hong Kong/epidemiología , Humanos , Modelos Logísticos , Masculino , Obstrucción Nasal/complicaciones , Oportunidad Relativa , Otitis Media con Derrame/etiología , Otoscopía , Factores de Riesgo , Tonsilitis/complicacionesRESUMEN
OBJECTIVE: On-pump beating heart coronary artery surgery provides the opportunity to examine the isolated effect of cardiopulmonary bypass. This prospective randomized study compares the early clinical outcomes and inflammatory response of patients undergoing elective on-pump and off-pump beating heart coronary artery bypass grafting. METHOD AND PATIENTS: Thirty-seven consecutive patients undergoing elective coronary artery bypass grafting were recruited from a pool of 73 patients, with 19 patients randomized to on-pump beating heart surgery and 18 patients to off-pump coronary bypass surgery. Intraoperative events and postoperative outcomes were recorded. Plasma levels of interleukin-6, interleukin-8, and interleukin-10, tumor necrosis factor-alpha, and vascular cell adhesion molecule-1 were measured before the operation, intraoperatively, after the operation, and 4, 24, and 48 hours thereafter. RESULTS: There was no significant difference in clinical outcomes between the 2 groups. The operating time was longer and consumption of platelets was greater for the on-pump beating heart group. There was no postoperative mortality or major complication in either group. There was significant elevation in the levels of interleukin-6, interleukin-8, and interleukin-10 and tumor necrosis factor-alpha during and immediately after the operations in the on-pump beating heart group when compared with the off-pump group. Levels of interleukin-8 (P =.01) and tumor necrosis factor-alpha (P =.0004) remained significantly elevated 4 hours after the operation in the on-pump beating heart group. The level of vascular adhesion molecule dropped significantly during the operation but was elevated 4 hours (P =.026) after the operation in the on-pump beating heart group. CONCLUSION: The use of cardiopulmonary bypass alone without global myocardial ischemia secondary to aortic crossclamping and cardioplegic cardiac arrest can trigger intense inflammatory responses.
Asunto(s)
Puente de Arteria Coronaria/métodos , Enfermedad Coronaria/cirugía , Citocinas/metabolismo , Mediadores de Inflamación/metabolismo , Anciano , Puente Cardiopulmonar/métodos , Moléculas de Adhesión Celular/análisis , Enfermedad Coronaria/diagnóstico , Citocinas/análisis , Femenino , Humanos , Mediadores de Inflamación/análisis , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico/métodos , Periodo Posoperatorio , Probabilidad , Pronóstico , Estudios Prospectivos , Valores de Referencia , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: In Hong Kong, it has been projected that, by the year 2010, there will be 0.86 million persons aged 65 or older. The demand for residential care places continues to rise. Information on the survival of older persons will allow better management of care in institutional settings. OBJECTIVE: The Weibull model was developed to predict the 18-month survival of a group of Chinese nursing home residents. METHODS: In this prospective cohort study, 590 older residents from four nursing homes with different levels of care were enrolled. The main outcome measure was survival at 18 months. Information on subject demographics, clinical data and disability levels as measured by the Patient Assessment Instrument (PAI) was collected at baseline. Life expectancies were derived from accelerated failure time models. RESULTS: Independent predictors of decreased survival derived from the Weibull model included increased age, male gender, diagnosis of cancer, presence of malnutrition and functional dependence. Significant interaction was observed between male gender and PAI score. The goodness of fit of the model was satisfactory. CONCLUSIONS: From this study, the model for predicting life expectancy in nursing home residents can assist policy makers in planning long-term care. It can also guide clinicians to make more appropriate management decisions for their older patients.