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2.
Sleep Med ; 96: 57-63, 2022 08.
Article in English | MEDLINE | ID: mdl-35605347

ABSTRACT

BACKGROUND: Although sleep disturbances and insomnia are common among Internally Displaced Persons (IDPs), these disorders remain largely understudied among victims fleeing ethnoreligious genocide. The Insomnia Severity Index (ISI), though a widely used measure of insomnia, has not been translated, cross-culturally adapted, nor validated in common African languages. This paper aimed to translate, adapt and validate the ISI scale into Hausa, the most widely spoken non-Indo-European language in African continent. METHODS: A six-stage validation model was used for the translation and adaptation of the ISI into Hausa [(ISI-Hausa), Item-Content Validity Index (I-CVI)=0.9 to 1.0]. The tool was administered among IDPs residing in Maiduguri, North-Eastern Nigeria, from October to November 2019. A total of 281 participants from six camps were recruited via convenience sampling. The psychometric properties of the scale were assessed using an Exploratory Factor Analysis (EFA), Cronbach's alpha (α) and Intraclass Correlation Coefficients (ICC) for determining factor structure, internal consistency and test-retest reliability, respectively. RESULTS: Exploratory factor reduction resulted in a two-factor solution, with " severity of insomnia " identified as the construct for Factor 1 and " impact of insomnia " as the construct for Factor 2. Factor 1 consisted of four scale items and Factor 2 consisted of three items. Factor loadings for each item ranged from 0.535-0.812. The scale demonstrated acceptable internal consistency (α=0.72) and good test-retest reliability (ICC=0.72) (p<0.001). CONCLUSION: The ISI-Hausa scale is a psychometrically sound and culturally relevant tool for assessing the severity and impact of insomnia among Hausa speaking IDPs in Africa.


Subject(s)
Refugees , Sleep Initiation and Maintenance Disorders , Cross-Cultural Comparison , Humans , Language , Nigeria , Psychometrics/methods , Reproducibility of Results , Sleep Initiation and Maintenance Disorders/diagnosis , Surveys and Questionnaires
3.
J Nutr Health Aging ; 25(4): 425-432, 2021.
Article in English | MEDLINE | ID: mdl-33786558

ABSTRACT

OBJECTIVES: The World Health Organization developed the Risk Factor Model for Falls to describe fall risks in a comprehensive manner. However, there was a lack of study adopting such framework in quantifying falls risk from different factors in a single model. Therefore, this study examined the risk factors from four domains in the Risk Factor Model for Falls among older adults. DESIGN: Secondary data analysis of 10-year assessment records of the Minimum Data Set-Home Care instrument. SETTING: Hong Kong. PARTICIPANTS: 89,100 community-dwelling adults aged 65 and over who first applied for publicly funded long-term care services from 2005 to 2014. MEASUREMENTS: The Minimum Data Set-Home Care instrument was used to ascertain older adults' care needs and match them with appropriate services. Additionally, meteorological records from the same period were extracted from the Hong Kong Observatory. The logistic regression model was used to examine risk factors and their associations with falls. RESULTS: In total 70 factors were included in the analysis, of which 37 were significantly associated with falls. Behavioral risk factors generally had greater odds ratios of falling, as compared with biological, socioeconomic, and environmental factors. Out of all significant factors, functional status, alcohol drinking, and locomotion outdoors had the largest odds ratios of falling. CONCLUSION: Behavioral risk factors for falls are of remarkable influence yet are modifiable among older adults. Hence, falls prevention programs may need to prioritize addressing these factors.


Subject(s)
Accidental Falls/statistics & numerical data , Aged , Aged, 80 and over , Female , Humans , Independent Living , Male , Risk Factors , World Health Organization
4.
Hong Kong Med J ; 26(5): 404-412, 2020 10.
Article in English | MEDLINE | ID: mdl-33093243

ABSTRACT

INTRODUCTION: This study aimed to develop and validate a brief practitioner-friendly health literacy screening tool, called Rapid Estimate of Inadequate Health Literacy (REIHL), that estimates patients' health literacy inadequacy in demanding clinical settings. METHODS: This is a methodological study of 304 community-dwelling older adults recruited from one community health centre and five district elderly community centres. Logistic regression models were used to identify the coefficients of the REIHL score's significant factors. Receiver operating characteristic (ROC) curve analysis was then used to assess the REIHL's sensitivity and specificity. Path analysis was employed to examine the REIHL's criterion validity with the Chinese Health Literacy Scale for Chronic Care and concurrent validity with self-rated health scale and the Geriatric Depression Scale-15. RESULTS: The REIHL has scores ranging from 0 to 23. It had 76.9% agreement with the Chinese Health Literacy Scale for Chronic Care. The area under the ROC curve for predicting health literacy inadequacy was 0.82 (95% confidence interval=0.78-0.87, P<0.001). The ROC curve of the REIHL showed that scores ≥11 had a sensitivity of 77.8% and specificity of 75.6% for predicting health literacy inadequacy. The path analysis model showed excellent fit (Chi squared [2, 304] 0.16, P=0.92, comparative fit index 1.00, root mean square error of approximation <0.001, 90% confidence interval=0.00-0.04), indicating that the REIHL has good criterion and concurrent validity. CONCLUSION: The newly developed REIHL is a practical tool for estimating older adults' inadequate health literacy in clinical care settings.


Subject(s)
Geriatric Assessment/methods , Health Literacy , Independent Living/psychology , Mass Screening/standards , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Hong Kong , Humans , Logistic Models , Male , Middle Aged , ROC Curve , Reproducibility of Results , Sensitivity and Specificity
5.
Hong Kong Med J ; 25(6): 473-482, 2019 12.
Article in English | MEDLINE | ID: mdl-31796643

ABSTRACT

Dementia is one of the most costly, disabling diseases associated with ageing, yet it remains underdiagnosed in primary care. In this article, we present the comprehensive approach illustrated with a classical case for diagnosing dementia which can be applied by healthcare professionals in primary care. This diagnostic approach includes history taking and physical examination, cognitive testing, informant interviews, neuropsychological testing, neuroimaging, and the utility of cerebrospinal fluid biomarkers. For the differential diagnosis of cognitive impairment, the differences and similarities among normal ageing, mild cognitive impairment, depression, and delirium are highlighted. As primary care physicians are playing an increasingly prominent role in the caring of elderly patients in an ageing population, their role in the diagnosis of dementia should be strengthened in order to provide a quality care for patients with dementia.


Subject(s)
Dementia/diagnosis , Health Personnel , Humans , Neuropsychological Tests , Primary Health Care
6.
J Nutr Health Aging ; 23(10): 943-948, 2019.
Article in English | MEDLINE | ID: mdl-31781723

ABSTRACT

BACKGROUND: Cognitive frailty is a condition where physical frailty and mild cognitive impairment (MCI) co-exist. It is associated with increased risk of dementia and dependency. Previous studies reported that malnutrition and depression are associated with physical frailty and MCI; however, their relationships with cognitive frailty remained to be explored. The aims of this study were to examine the association of nutrition and depression with cognitive frailty, in comparison to having physical frailty or MCI alone. METHODS: This study employed a cross-sectional design. Data collection was conducted in the community settings on the older people without dementia. Dependent variables were cognitive frailty, physical frailty, and MCI. The independent variables were depression and nutrition. Multi-nominal regression was employed to examine the relationships between the dependent and independent variables. The associations were adjusted by four known co-variates, including age, gender, education and APOE ε4 carrier status. RESULTS: A total of 185 participants were recruited from four community centres and one elderly hostel and completed the data collection. Approximately 44.9% of the older people with physical frailty and 82.5% of elderly with MCI belonged to cognitive frailty. Multi-nominal regression models showed that depression is positively associated with cognitive frailty and with physical frailty, but not associated with solely MCI. Nutrition is negatively associated with cognitive frailty, but not associated with physical frailty or MCI alone. CONCLUSION: Cognitive frailty is associated with malnutrition and depression. Therapeutic interventions managing depression and malnutrition may focus the older people with cognitive frailty to improve efficacy and cost-effectiveness.


Subject(s)
Depression/etiology , Frail Elderly/psychology , Frailty/etiology , Frailty/psychology , Nutritional Status/physiology , Aged , Aged, 80 and over , Cross-Sectional Studies , Data Collection , Depression/psychology , Female , Humans , Independent Living , Male
7.
Soc Psychiatry Psychiatr Epidemiol ; 53(10): 1039-1049, 2018 10.
Article in English | MEDLINE | ID: mdl-29860568

ABSTRACT

PURPOSE: Depression literacy refers to the ability to recognize depression and make informed decisions about its treatment. To date, relatively little research has been done to examine depression literacy in the Western Pacific region. Given the pervasiveness of depression and the need to enhance mental health care in this region, it is important to gain a better understanding of depression literacy and health-seeking behaviors in this part of the world. METHODS: This mixed-methods study utilized a convergent parallel design to examine depression literacy and the associated health-seeking attitudes among urban adults from three countries-Cambodia, Philippines, and Fiji. A total of 455 adults completed a quantitative survey on depression knowledge, attitudes, and professional help seeking. Separately, 56 interviewees from 6 focus groups provided qualitative data on their impression and knowledge of depression and mental illness within the context of their local communities. RESULTS: Overall, results showed that depression knowledge was comparatively lower in this region. Controlling for differences across countries, higher knowledge was significantly associated with more positive attitudes towards mental illness (B = - 0.28, p = 0.025) and professional help seeking (B = 0.20, p < 0.001). Financial stability, such as employment, was also a salient factor for help seeking. CONCLUSIONS: This study was the first to provide a baseline understanding on depression literacy and highlights the need to increase public knowledge on depression in the Western Pacific. Culturally congruent recommendations on enhancing depression literacy in this region, such as anti-stigma campaigns, use of financial incentives, and family-based approach in health education, are discussed.


Subject(s)
Depression/psychology , Health Knowledge, Attitudes, Practice , Health Literacy , Help-Seeking Behavior , Adult , Cambodia , Female , Fiji , Focus Groups , Humans , Male , Middle Aged , Philippines , Qualitative Research , Social Stigma , Surveys and Questionnaires , Young Adult
8.
Article in English | MEDLINE | ID: mdl-29943118

ABSTRACT

In the original publication of this article, Acknowledgements Section was not included. The Acknowledgements are given below. The original article has been corrected.

9.
Leukemia ; 31(1): 222-233, 2017 01.
Article in English | MEDLINE | ID: mdl-27457538

ABSTRACT

The c-MYB transcription factor is a key regulator of hematopoietic cell proliferation and differentiation, and dysregulation of c-MYB activity often associates with various hematological disorders. Yet, its pathogenic role remains largely unknown due to lack of suitable animal models. Here, we report a detail characterization of a c-myb-gfp transgenic zebrafish harboring c-Myb hyperactivity (named c-mybhyper). This line exhibits abnormal granulocyte expansion that resembles human myelodysplastic syndrome (MDS) from embryonic stage to adulthood. Strikingly, a small portion of c-mybhyper adult fish develops acute myeloid leukemia-like or acute lymphoid leukemia-like disorders with age. The myeloid and lymphoid malignancies in c-mybhyper adult fish are likely caused by the hyperactivity of c-myb, resulting in the dysregulation of a number of cell-cycle-related genes and hyperproliferation of hematopoietic precursor cells. Finally, treatment with c-myb target drug flavopiridol can relieve the MDS-like symptoms in both c-mybhyper embryos and adult fish. Our study establishes a zebrafish model for studying the cellular and molecular mechanisms underlying c-Myb-associated leukemogenesis as well as for anti-leukemic drug screening.


Subject(s)
Disease Models, Animal , Leukemia, Myeloid, Acute/etiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/etiology , Proto-Oncogene Proteins c-myb/metabolism , Animals , Animals, Genetically Modified , Cell Cycle/genetics , Cell Proliferation/genetics , Hematopoietic Stem Cells/cytology , Humans , Zebrafish
10.
J Mech Behav Biomed Mater ; 66: 58-67, 2017 02.
Article in English | MEDLINE | ID: mdl-27838591

ABSTRACT

A drug-free procedure for killing malignant cells in a cell-type specific manner would represent a significant breakthrough for leukemia treatment. Here, we show that mechanically vibrating a cell in a specific oscillation condition can significantly promote necrosis. Specifically, oscillating the cell by a low-power laser trap at specific frequencies of a few Hz was found to result in increased death rate of 50% or above in different types of myelogenous leukemia cells, while normal leukocytes showed very little response to similar laser manipulations. The alteration of cell membrane permeability and cell volume, detected from ethidium bromide staining and measurement of intracellular sodium ion concentration, together with the observed membrane blebbing within 10min, suggest cell necrosis. Mechanics modelling reveals severe distortion of the cytoskeleton cortex at frequencies in the same range for peaked cell death. The disruption of cell membrane leading to cell death is therefore due to the cortex distortion, and the frequency at which this becomes significant is cell-type specific. Our findings lay down a new concept for treating leukemia based on vibration induced disruption of membrane in targeted malignant cells.


Subject(s)
Cell Death , Cell Nucleus/pathology , Cytoskeleton/pathology , Optical Tweezers , Vibration , Apoptosis , Cell Line, Tumor , Cell Membrane Permeability , Cell Size , Cytoplasm , Humans , Leukemia, Myeloid
11.
Leukemia ; 31(5): 1206-1216, 2017 05.
Article in English | MEDLINE | ID: mdl-27811851

ABSTRACT

Mutations in the human myeloproliferative leukemia (MPL) protein gene are known to cause congenital amegakaryocytic thrombocytopenia (CAMT). The prognosis of this heritable disorder is poor and bone marrow transplantation is the only effective treatment. Here, by using the TALEN (transcription activator-like effector nuclease) technology, we created a zebrafish mpl mutant to model human CAMT. Disruption of zebrafish mpl lead to a severe reduction in thrombocytes and a high bleeding tendency, as well as deficiencies in adult hematopoietic stem/progenitor cells. We further demonstrated that thrombocytopenia in mpl mutant zebrafish was caused by impaired Tpo/Mpl/Jak2 signaling, resulting in reduced proliferation of thrombocyte precursors. These results indicate that mpl mutant zebrafish develop thrombocytopenia resembling the human CAMT. To utilize fully zebrafish to study thrombocyte biology and thrombocytopenia disorders, we generated a transgenic reporter line Tg(mpl:eGFP)smu4, in which green fluorescent protein (GFP) expression was driven by the mpl promoter. Detailed characterization of Tg(mpl:eGFP)smu4 fish confirmed that the thrombocyte lineage was specifically marked by GFP expression. In conclusion, we generated the first transmissible congenital thrombocytopenia zebrafish model mimicking human CAMT and a thrombocyte-specific transgenic line. Together with Tg(mpl:eGFP)smu4, mpl mutant zebrafish provide a useful tool for drug screening and study of thrombocytopoiesis.


Subject(s)
Disease Models, Animal , Receptors, Thrombopoietin/genetics , Thrombocytopenia/pathology , Zebrafish , Animals , Blood Platelets/pathology , Congenital Bone Marrow Failure Syndromes , Genes, Reporter , Green Fluorescent Proteins/genetics , Humans , Janus Kinase 2/metabolism , Receptors, Thrombopoietin/metabolism , Signal Transduction , Thrombopoietin/metabolism
12.
J Nutr Health Aging ; 21(1): 3-10, 2017.
Article in English | MEDLINE | ID: mdl-27999843

ABSTRACT

OBJECTIVE: To compare the preference of food saltiness and the willingness to consume low-sodium food among hypertensive older people, non-hypertensive older people and non-hypertensive young people in a Chinese population. DESIGN: A cross-sectional study based on a quota sample. Three saltiness options (low-sodium, medium-sodium and high-sodium) of soup and bread were offered to each participant who rated the taste of each food on a 5-point Likert scale. Then, the participants rated their willingness to consume the low-sodium content foods on a 5-point Likert scale, given they were informed of the benefit of the low-sodium option. Generalised linear mixed model and multiple linear regression were used to analyse the data. SETTING: Elderly centres and community centres in Hong Kong. PARTICIPANTS: Sixty hypertensive older people, 49 non-hypertensive older people and 60 non-hypertensive young people were recruited from June to August 2014. MEASUREMENTS: The tastiness score and the willingness score were the primary outcome measures. The Chinese Health Literacy Scale for Low Salt Consumption - Hong Kong population (CHLSalt-HK) was also assessed. RESULTS: The tastiness rating of the high-sodium option of soup was significantly lower than the medium-sodium option (p<0.001), but there was no significant difference between the low-sodium and the medium-sodium options (p=0.204). For bread, tastiness rating of the low-sodium option and the high-sodium option were significantly lower than the medium-sodium option (p<0.001 for both options). The tastiness score of soup did not have significant difference across the groups (p=0.181), but that of bread from the hypertensive older adults (p=0.012) and the non-hypertensive older adults (p=0.006) was significantly higher than the non-hypertensive young adults. Higher willingness rating to consume the low-sodium option was significantly (p<0.001) associated with higher tastiness rating of the low-sodium option of soup and bread, and weakly associated with higher health literacy of low salt intake (soup: p=0.041; bread: p=0.024). Hypertensive older adults tended to be more willing to consume the low-sodium option than non-hypertensive older adults for soup (p=0.009), there was insignificant difference between non-hypertensive older adults and non-hypertensive young adults (p=0.156). For bread, there was insignificant difference in willingness rating to consume low-sodium option (p=0.375). CONCLUSION: Older people are at a higher risk of hypertension, reduction of salt intake is important for them to reduce their risk of cardiovascular diseases. There is room for reducing the sodium content of soup, while the sodium in bread should be reduced progressively. Improving the taste of low-sodium food may help to promote reduction in dietary sodium intake.


Subject(s)
Asian People/psychology , Diet, Sodium-Restricted/psychology , Food Preferences/psychology , Sodium Chloride, Dietary/administration & dosage , Adolescent , Adult , Aged , Blood Pressure/drug effects , Case-Control Studies , Cross-Sectional Studies , Female , Hong Kong , Humans , Hypertension/diet therapy , Hypertension/drug therapy , Linear Models , Male , Middle Aged , Socioeconomic Factors , Taste , Young Adult
13.
Blood Cancer J ; 6(7): e442, 2016 07 08.
Article in English | MEDLINE | ID: mdl-27391574

ABSTRACT

Clinical outcome and mutations of 96 core-binding factor acute myeloid leukemia (AML) patients 18-60 years old were examined. Complete remission (CR) after induction was 94.6%. There was no significant difference in CR, leukemia-free-survival (LFS) and overall survival (OS) between t(8;21) (N=67) and inv(16) patients (N=29). Univariate analysis showed hematopoietic stem cell transplantation at CR1 as the only clinical parameter associated with superior LFS. Next-generation sequencing based on a myeloid gene panel was performed in 72 patients. Mutations in genes involved in cell signaling were associated with inferior LFS and OS, whereas those in genes involved in DNA methylation were associated with inferior LFS. KIT activation loop (AL) mutations occurred in 25 patients, and were associated with inferior LFS (P=0.003) and OS (P=0.001). TET2 mutations occurred in 8 patients, and were associated with significantly shorter LFS (P=0.015) but not OS. Patients negative for KIT-AL and TET2 mutations (N=41) had significantly better LFS (P<0.001) and OS (P=0.012) than those positive for both or either mutation. Multivariate analysis showed that KIT-AL and TET2 mutations were associated with inferior LFS, whereas age ⩾40 years and marrow blast ⩾70% were associated with inferior OS. These observations provide new insights that may guide better treatment for this AML subtype.


Subject(s)
Core Binding Factors/genetics , Core Binding Factors/metabolism , DNA-Binding Proteins/genetics , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/metabolism , Mutation , Proto-Oncogene Proteins c-kit/metabolism , Proto-Oncogene Proteins/genetics , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Combined Modality Therapy , DNA Methylation , DNA Mutational Analysis , DNA-Binding Proteins/metabolism , Dioxygenases , Female , Hematopoietic Stem Cell Transplantation/methods , High-Throughput Nucleotide Sequencing , Humans , Leukemia, Myeloid, Acute/mortality , Leukemia, Myeloid, Acute/therapy , Male , Middle Aged , Prognosis , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins c-kit/genetics , Signal Transduction , Survival Analysis , Translocation, Genetic , Transplantation, Homologous , Young Adult
14.
J Hazard Mater ; 311: 100-14, 2016 Jul 05.
Article in English | MEDLINE | ID: mdl-26967646

ABSTRACT

Enhancement of fine particle (PM2.5) separation is important for cyclone separators to reduce any extra purification process required at the outlet. Therefore, the present experimental research was performed to explore the performance of cyclone separators modified with down-comer tubes at solid loading rates from 0 to 8.0 g/m(3) with a 10 m/s inlet velocity. The study proved the effectiveness of down-comer tubes in reducing the particle re-entrainment and increasing the finer separation with acceptable pressure drops, which was pronounced at low solid loading conditions. The experimental results were compared with theories of Smolik and Muschelknautz. Theories were acceptable for certain ranges, and theory breakdown was mainly due to the neglect of particle agglomeration, re-entrainment and the reduction of swirling energy, as well as the increase of wall friction due to presence of particles.

15.
Sci Rep ; 6: 22824, 2016 Mar 09.
Article in English | MEDLINE | ID: mdl-26956215

ABSTRACT

Suspended cells are difficult to be transfected by common biochemical methods which require cell attachment to a substrate. Mechanical oscillations of suspended cells at certain frequencies are found to result in significant increase in membrane permeability and potency for delivery of nano-particles and genetic materials into the cells. Nanomaterials including siRNAs are found to penetrate into suspended cells after subjecting to short-time mechanical oscillations, which would otherwise not affect the viability of the cells. Theoretical analysis indicates significant deformation of the actin-filament network in the cytoskeleton cortex during mechanical oscillations at the experimental frequency, which is likely to rupture the soft phospholipid bilayer leading to increased membrane permeability. The results here indicate a new method for enhancing cell transfection.


Subject(s)
Stress, Mechanical , Transfection/methods , Transformation, Genetic , Cell Line, Tumor , Cell Membrane/physiology , Endocytosis , Genes , Humans , Nanostructures , Permeability
17.
Leukemia ; 28(4): 865-70, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23842425

ABSTRACT

Circulating Epstein-Barr virus (EBV) DNA is a biomarker of EBV-associated malignancies. Its significance in natural killer/T-cell lymphoma treated with the novel regimen SMILE was investigated. EBV DNA was quantified with a World Health Organization EBV standard in 910 plasma samples collected during 230 courses of SMILE in 56 patients. Median presentation EBV DNA was 1900 (0-1.4 × 10(7)) IU/ml. Presentation EBV DNA was significantly associated with tumor load and treatment response. To examine lymphoma chemosensitivity, EBV DNA changes after SMILE were evaluated. EBV DNA after SMILE (I) significantly correlated with tumor load and treatment response. Two dynamic parameters were further analyzed: negative EBV DNA after SMILE (I) and EBV DNA change patterns during treatment (A: persistently undetectable; B: persistently detectablepresentation). Negative EBV DNA after SMILE (I) and pattern A EBV DNA change significantly correlated with lower tumor load and superior outcome. Multivariate analysis involving presentation features, international prognostic index (IPI), Korean prognostic score and EBV DNA parameters showed that negative EBV DNA after SMILE (I) had the most significant impact (P<0.001) on overall survival and pattern A EBV DNA change had the most significant impact (P=0.002) on disease-free survival. Presentation EBV DNA, IPI and Korean prognostic scores were not independent prognostic factors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , DNA, Viral/blood , Herpesvirus 4, Human/isolation & purification , Killer Cells, Natural/pathology , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/virology , Adolescent , Adult , Aged , Aged, 80 and over , Asparaginase/administration & dosage , Dexamethasone/administration & dosage , Etoposide/administration & dosage , Female , Humans , Ifosfamide/administration & dosage , Lymphoma, T-Cell/mortality , Lymphoma, T-Cell/pathology , Male , Methotrexate/administration & dosage , Middle Aged , Prognosis
19.
Intern Med J ; 43(5): 541-6, 2013 May.
Article in English | MEDLINE | ID: mdl-23279203

ABSTRACT

BACKGROUND: Invasive fungal disease (IFD) is an important problem complicating the therapy of haematologic patients. AIM: This study aimed to provide data on the epidemiology of IFD in an Asian teaching hospital, as well as the prescription practice of antifungal drugs. METHOD: We conducted a retrospective review of 275 haematologic patients who were prescribed antifungal drugs in a 4-year period (2007-2010), of whom 130 (47%) had undergone haematopoietic stem cell transplantation. RESULTS: Antifungal prophylaxis with either fluconazole or itraconazole was given in 214 patients (78%). There were 414 prescriptions of antifungal drugs (including liposomal amphotericin B, voriconazole, caspofungin, micafungin, anidulafungin), of which 361 prescriptions were empirical. There were 14 patients with proven IFD, 11 of whom had breakthrough infection while on itraconazole prophylaxis. Interestingly, seven of these cases were due to infection by itraconazole-sensitive candida. CONCLUSION: These results provide important epidemiologic data necessary for the formulation of strategies for prevention and treatment of IFD in Asian patients.


Subject(s)
Antifungal Agents/therapeutic use , Hematologic Diseases/drug therapy , Hematologic Diseases/epidemiology , Hospitals, Teaching/trends , Mycoses/drug therapy , Mycoses/epidemiology , Adult , Aged , Aged, 80 and over , Asia/epidemiology , Female , Hospitals, Teaching/methods , Hospitals, University/trends , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
20.
Leukemia ; 27(2): 260-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22797419

ABSTRACT

Internal tandem duplication (ITD) of the fms-like tyrosine kinase 3 (FLT3) gene is a gain-of-function mutation common in acute myeloid leukaemia (AML). It is associated with inferior prognosis and response to chemotherapy. Single base mutations at the FLT3 tyrosine kinase domain (TKD) also leads to a gain of function, although its prognostic significance is less well defined because of its rarity. The clinical benefits of FLT3 inhibition are generally limited to AML with FLT3-ITD. However, responses are transient and leukaemia progression invariably occurs. There is compelling evidence that leukaemia clones carrying both ITD and TKD mutations appear when resistance to FLT3 inhibitors occurs. Interestingly, the emergence of double ITD and TKD mutants can be recapitulated in vitro when FLT3-ITD+ leukaemia cell lines are treated with mutagens and FLT3 inhibitors. Furthermore, murine xenotransplantation models also suggest that, in some cases, the FTL3-ITD and TKD double mutants actually exist in minute amounts before treatment with FLT3 inhibitors, expand under the selection pressure of FLT3 inhibition and become the predominant resistant clone(s) during the drug-refractory phase. On the basis of this model of clonal evolution, a multipronged strategy using more potent FLT3 inhibitors, and a combinatorial approach targeting both FLT3-dependent and FLT3-independent pathways, will be needed to improve outcome.


Subject(s)
Antineoplastic Agents/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , fms-Like Tyrosine Kinase 3/antagonists & inhibitors , Animals , Humans , Leukemia, Myeloid, Acute/enzymology
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