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1.
Med J Malaysia ; 77(6): 655-660, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36448381

RESUMO

INTRODUCTION: Burnout is a psychological problem which is becoming more prevalent among medical professionals resulting in various negative outcomes. Physical activity has been found to be an effective method in alleviating burnout. The aim of this study was to determine the association between physical activity and burnout among postgraduate anaesthesia trainees in Malaysia. The study also intended to determine the level of physical activity among trainees, the factors affecting this practice, and the prevalence of burnout among anaesthesia trainees. MATERIALS AND METHODS: An online self-administered questionnaire was sent out to all postgraduate anaesthesia trainees between August 2020 and January 2021 via email and respondents were recruited on a voluntary basis. RESULTS: The prevalence of burnout among postgraduate anaesthesia trainees was high (54%). This prevalence was higher among trainees with low a level of physical activity. Half of the trainees (50.8%) engaged in moderate physical activity while only 12% reported a high level of physical activity. The postgraduate study year was found to be a significant factor affecting the practice of physical activity. CONCLUSION: There is a significant association between physical activity and burnout among postgraduate anaesthesia trainees in Malaysia. Physical activity has the potential to be an essential method of reducing burnout. Hence, measures should be implemented to improve the practice of physical activity among healthcare professionals in order to reduce workplace burnout.


Assuntos
Anestesia , Esgotamento Psicológico , Humanos , Malásia/epidemiologia , Exercício Físico , Local de Trabalho
2.
Neuropathol Appl Neurobiol ; 46(2): 125-141, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31179553

RESUMO

AIMS: Aggressive meningioma remains incurable with neither chemo- nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression. METHODS: Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression-free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked-down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM-Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)-pretreated or control IOMM-Lee cells were implanted subcutaneously in nude mice. RESULTS: FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of ß-catenin, cyclin D1, p21, interleukin-8, vascular endothelial growth factor-A, PLAU, and epithelial-to-mesenchymal transition-related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model. CONCLUSIONS: Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.


Assuntos
Proteína Forkhead Box M1/metabolismo , Regulação Neoplásica da Expressão Gênica , Meningioma/metabolismo , Animais , Encéfalo/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/metabolismo , Intervalo Livre de Progressão
3.
Ultrasound Obstet Gynecol ; 55(3): 383-390, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31115076

RESUMO

OBJECTIVES: To determine the incidence of chromosomal abnormalities, submicroscopic chromosomal abnormalities and RASopathy-disorder (RD) pathogenic variants in a cohort of pregnancies with nuchal translucency thickness (NT) ≥ 3.5 mm, and to propose a clinical protocol for surveillance of this group of patients. METHODS: This was a retrospective chart review of patients referred to The Prenatal Diagnosis and Medical Genetics Program at Mount Sinai Hospital between January 2013 and December 2015, due to NT ≥ 3.5 mm, who underwent chorionic villus sampling or amniocentesis. Patients underwent extensive genetic counseling prior to invasive procedures and testing. Quantitative fluorescence polymerase chain reaction (QF-PCR) was performed as the first-line test for aneuploidy. If the result was negative, patients underwent karyotyping and/or chromosomal microarray analysis (CMA), and if the findings were normal, they had testing for RD pathogenic variants, which included nine known genes. Patients also underwent detailed fetal ultrasound examinations and echocardiography, performed by expert operators. RESULTS: A total of 226 eligible patients were identified. In 116/226 (51.3%) patients, QF-PCR identified a chromosomal aneuploidy. The remaining 110/226 (48.7%) patients had further genetic testing. Karyotyping/CMA detected an abnormal/pathogenic cytogenetic result in 9/110 (8.2%) patients, as well as five variants of unknown significance (VOUS). RD testing yielded three pathogenic variants (3/103), giving a detection rate of 2.9%, and one VOUS. The optimal NT cut-off for RD screening was 7.9 mm in this population. In 92/110 (83.6%) patients, the genetic investigations were normal. Of these pregnancies, an early (14-16 weeks' gestation) detailed fetal ultrasound examination identified a structural abnormality in 24 (26.1%), 15 (16.3%) had an abnormal detailed ultrasound examination at 18-22 weeks' gestation and fetal echocardiography showed a cardiac abnormality in nine (9.8%). The birth outcome in the 83 pregnancies that had normal genetic investigations and known outcome included seven (8.4%) cases of termination of pregnancy, seven (8.4%) cases of intrauterine fetal death and 69 (83.1%) cases of live birth. Nine (9.8%) patients were lost to follow-up. CONCLUSIONS: Both CMA and molecular testing for RD are important investigations in pregnancies with NT ≥ 3.5 mm. The use of genetic testing combined with fetal ultrasound examination provides valuable information that can influence pregnancy outcome, and provide recurrence risks, in this patient population. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Transtornos Cromossômicos/diagnóstico , Genes ras/genética , Doenças Genéticas Inatas/diagnóstico , Análise em Microsséries , Medição da Translucência Nucal , Adulto , Amniocentese , Aneuploidia , Amostra da Vilosidade Coriônica , Aberrações Cromossômicas/embriologia , Transtornos Cromossômicos/embriologia , Transtornos Cromossômicos/epidemiologia , Feminino , Feto/embriologia , Aconselhamento Genético , Doenças Genéticas Inatas/embriologia , Doenças Genéticas Inatas/epidemiologia , Doenças Genéticas Inatas/genética , Mutação em Linhagem Germinativa , Idade Gestacional , Humanos , Incidência , Cariotipagem , Gravidez , Resultado da Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-Natal
4.
J Eur Acad Dermatol Venereol ; 34(4): 897-903, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31858658

RESUMO

BACKGROUND: Recent data demonstrated that an altered basal membrane, activated melanocytes and secreted factors from keratinocytes but also fibroblasts and endothelial cells are involved in the pathophysiology of melasma. OBJECTIVES: To evaluate the efficacy and tolerability on melasma of a new topical skin-lightening cosmetic product combination (CCP) targeting several factors identified to be involved in melasma pathogenesis compared to 4% hydroquinone (HQ). METHODS: Forty-three women with melasma were enrolled in a 12-week double-blind, randomized, parallel-group trial and treated with CCP or 4% HQ cream. Efficacy was evaluated with the modified Melasma Area Severity Index (mMASI) score and colorimetric change. Cutaneous tolerability and patient satisfaction were also investigated. RESULTS: The mMASI score decreased for both products from baseline and over the study period. At week 12, 90% of the subjects who received the combination products had an improvement in pigmentation vs. 79% with HQ. Similarly, both products significantly increased Individual Typological Angle parameters. For both measures, no statistically significant difference was observed between CCP and HQ in terms of change from baseline. CPP was very well tolerated. CONCLUSIONS: Cosmetic product combination is as effective as HQ in the management of facial dyspigmentation and represents a safe alternative.


Assuntos
Cosméticos/administração & dosagem , Melanose/tratamento farmacológico , Melanose/fisiopatologia , Administração Tópica , Adulto , Método Duplo-Cego , Células Endoteliais/efeitos dos fármacos , Feminino , Fibroblastos/efeitos dos fármacos , Humanos , Hidroquinonas/administração & dosagem , Melanócitos/efeitos dos fármacos , Pessoa de Meia-Idade , Satisfação do Paciente , Pigmentação da Pele , Protetores Solares/administração & dosagem , Inquéritos e Questionários
5.
Med J Malaysia ; 75(1): 43-46, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32008019

RESUMO

INTRODUCTION: Preoperative dialysis-dependent renal failure is a strong independent risk factor for in-hospital mortality and morbidity after open heart surgery. This retrospective study analyses the early outcome in dialysis-dependent renal failure patients who underwent elective open-heart surgery in the Institut Jantung Negara (IJN). METHODS: We retrospectively analyse a series of 228 consecutive postoperative patients with dialysis-dependent (end stage renal failure (ESRF)) admitted to the adult cardiothoracic ICU in IJN between January 2012 and December 2016. RESULTS: The overall early mortality rate included 34 patients (15.8%). Patients with ESRF underwent combined procedure recorded a very high mortality rate at 56.3%. Twenty-four patients (11.2%) needed resternotomy for postoperative bleeding or cardiac temponade. Postoperative mediastinitis rate was high, involving 13 patients (6%). The neurological and gastrointestinal complications rate were recorded at 2.3% (5 patients) and 6% (13 patients) respectively. In the group of patients (n=199) with sinus rhythm during the preoperative period, 100 patients (50.3%) developed postoperative AF. 77 patients (35.8%) stayed in hospital for more than 14 days. CONCLUSIONS: dialysis-dependent patients undergoing cardiac surgery poses higher perioperative risk of mortality and morbidity of 3-4 times higher compared to those patients with normal renal function. IJN shows acceptable perioperative risk of mortality and morbidity which is comparable to other centres.


Assuntos
Ponte de Artéria Coronária/efeitos adversos , Ponte de Artéria Coronária/mortalidade , Falência Renal Crônica , Complicações Pós-Operatórias/mortalidade , Diálise Renal , Idoso , Feminino , Humanos , Falência Renal Crônica/terapia , Malásia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Med J Malaysia ; 75(1): 12-17, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32008013

RESUMO

INTRODUCTION: This study looked into the different anatomical locations of pain and their trajectories within the first two weeks after Posterior Spinal Fusion (PSF) surgery for Adolescent Idiopathic Scoliosis (AIS). METHODS: We prospectively recruited patients with Adolescent Idiopathic Scoliosis (AIS) scheduled for PSF surgery. The anatomical locations of pain were divided into four: (1) surgical wound pain; (2) shoulder pain; (3) neck pain; and (4) low back pain. The anatomical locations of pain were charted using the visual analogue pain score at intervals of 12, 24, 36, 48 hours; and from day-3 to -14. Patient-controlled analgesia (morphine), use of celecoxib capsules, acetaminophen tablets and oxycodone hydrochloride capsule consumption were recorded. RESULTS: A total of 40 patients were recruited. Patients complained of surgical wound pain score of 6.2±2.1 after surgery. This subsequently reduced to 4.2±2.0 by day-4, and to 2.4±1.3 by day-7. Shoulder pain scores of symptomatic patients peaked to 4.2±2.7 at 24 hours and 36 hours which then reduced to 1.8±1.1 by day-8. Neck pain scores of symptomatic patients reduced from 4.2±1.9 at 12 hours to 1.8±1.1 by day-4. Low back pain scores of symptomatic patients reduced from 5.3±2.3 at 12 hours to 1.8±1.1 by day- 12. CONCLUSIONS: Despite the presence of different anatomical locations of pain after surgery, surgical wound was the most significant pain and other anatomical locations of pain were generally mild. Surgical wound pain reduced to a tolerable level by day-4 when patients can then be comfortably discharged. This finding provides useful information for clinicians, patients and their caregivers.


Assuntos
Dor Pós-Operatória/fisiopatologia , Escoliose/cirurgia , Fusão Vertebral , Coluna Vertebral/anatomia & histologia , Adolescente , Feminino , Humanos , Malásia/epidemiologia , Masculino , Dor Pós-Operatória/epidemiologia , Estudos Prospectivos
7.
J Hum Nutr Diet ; 32(2): 175-184, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30412327

RESUMO

BACKGROUND: Elimination diets required for the management of food allergies increase the risk for poor growth in children. Currently, no worldwide data exist on this topic and limited published data exist on the impact of atopic comorbidity, type of allergy and foods eliminated on growth. We therefore set out to perform a worldwide survey on growth and impacting factors in food allergic children. METHODS: A prospective growth survey was performed of children (aged 0-16 years) on an elimination diet with confirmed immunoglobulin (Ig)E and non-IgE mediated food allergies. Data collected included: weight-for-age, weight-for-height, height-for-age, head circumference, body mass index, type of food allergy and eliminated foods, allergic comorbidities and replacement milk/breast milk. Multivariable regression analysis was used to establish factors that affected growth. RESULTS: Data from 430 patients from twelve allergy centres were analysed: median age at diagnosis and data collection was 8 months and 23 months, respectively. Pooled data indicated that 6% were underweight, 9% were stunted, 5% were undernourished and 8% were overweight. Cow's milk elimination lead to a lower weight-for-height Z-scores than other food eliminations and mixed IgE and non-IgE mediated allergy had lower height-for-age Z-scores than IgE mediated allergy. Children with only non-IgE mediated allergies had lower weight-for-height and body mass index. Atopic comorbidities did not impact on growth. CONCLUSIONS: Stunting is more common in children with food allergies than low weight. Children particularly at risk of poor growth are those with non-IgE and mixed IgE and non-IgE mediated allergies, as well as those with cow's milk allergy.


Assuntos
Estatura/fisiologia , Peso Corporal/fisiologia , Hipersensibilidade Alimentar/fisiopatologia , Transtornos do Crescimento/etiologia , Magreza/etiologia , Adolescente , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Feminino , Hipersensibilidade Alimentar/complicações , Gráficos de Crescimento , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Análise de Regressão , Inquéritos e Questionários
9.
Age Ageing ; 47(2): 254-261, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29161361

RESUMO

Background: there is little evidence to suggest that older people today are living in better health than their predecessors did at the same age. Only a few studies have evaluated whether there are birth cohort effects on frailty, an indicator of health in older people, encompassing physical, functional and mental health dimensions. Objectives: this study examined longitudinal trajectories of frailty among Chinese older people in Hong Kong. Methods: this study utilised data from the 18 Elderly Health Centres of the Department of Health comprising a total of 417,949 observations from 94,550 community-dwelling Chinese people aged ≥65 years in one early birth cohort (1901-23) and four later birth cohorts (1924-29, 1930-35, 1936-41, 1942-47) collected between 2001 and 2012, to examine trajectories of the frailty index and how birth cohorts may have contributed to the trends using an age-period-cohort analysis. Results: more recent cohorts had higher levels of frailty than did earlier cohorts at the same age, controlling for period, gender, marital status, educational levels, socioeconomic status, lifestyle and social factors. Older age, being female, widowhood, lower education and smoking were associated with higher levels of frailty. Conclusion: more recent cohorts had higher levels of frailty than did earlier cohorts. Frailty interventions, coupled with early detection, should be developed to combat the increasing rates of frailty in Hong Kong Chinese.


Assuntos
Envelhecimento , Idoso Fragilizado , Fragilidade/epidemiologia , Determinantes Sociais da Saúde , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Escolaridade , Feminino , Fragilidade/diagnóstico , Avaliação Geriátrica , Hong Kong/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologia , Fatores de Tempo , Viuvez
11.
Child Care Health Dev ; 43(4): 556-565, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28480511

RESUMO

OBJECTIVE: The Ages and Stages Questionnaires Edition 3 (ASQ-3) are a well-validated international screen for developmental delays in young children. However, previous studies demonstrate variable scores between children eligible to take the same ASQ-3 interval. This study aimed to determine a relationship between age and ASQ-3 score for each screening interval. METHODS: This was a baseline exploratory cross-sectional study of infants under 2 years old evaluated for the Peruvian social programme Cuna Más. Participants were included in Cuna Más if they lived in districts with fewer than 2000 inhabitants or 400 homes, indicating a predominantly rural population. The appropriate ASQ-3 screening interval was administered to each subject. Subjects were divided into four 2-week chronological subgroups based on age within each 2-month screening window and aggregated across all 12 screening intervals. Fisher's exact test, analysis of variance and Bonferonni post hoc test were used to compare differences between age subgroups. Linear regression was performed to assess the relationship between ASQ-3 score and both aggregated and disaggregated age subgroup. RESULTS: A total of 5850 Peruvian infants were evaluated in 2013. Mean age was 13 ± 6.6 months, 50.7% were male and mean maternal education was 6.6 ± 4.0 years; 34.8% infants were stunted, 7.8% were underweight, 0.9% were wasted and 2% had age adjusted greater than 35 days for prematurity for ASQ-3 interval assignment. Mean total ASQ-3 was 42.2 ± 8.2. The ASQ-3 allocated 49.6% with suspected delay in one or more developmental areas. Before and after adjusting for wealth quintile, maternal education level, infant nutritional status and prematurity adjustment, age subgroup remained significantly associated with total ASQ-3 score (ß = 1.8, CI: 1.7-2.0, P < 0.001), sectional ASQ-3 score (all P < 0.001) and inversely associated with one or more scores indicating suspected developmental delay (P < 0.001). CONCLUSIONS: The ASQ-3 may underestimate the sensitivity of child development to small differences in age in this population.


Assuntos
Desenvolvimento Infantil/fisiologia , Deficiências do Desenvolvimento/diagnóstico , Programas de Rastreamento , Pais/psicologia , Fatores Etários , Estudos Transversais , Deficiências do Desenvolvimento/fisiopatologia , Deficiências do Desenvolvimento/psicologia , Escolaridade , Feminino , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/fisiopatologia , Humanos , Lactente , Transtornos da Nutrição do Lactente/epidemiologia , Transtornos da Nutrição do Lactente/fisiopatologia , Masculino , Testes Neuropsicológicos , Peru/epidemiologia , Valor Preditivo dos Testes , Psicometria , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Magreza/epidemiologia , Magreza/fisiopatologia
12.
Epidemiol Infect ; 144(8): 1584-91, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26645357

RESUMO

Three epidemic waves of human influenza A(H7N9) were documented in several different provinces in China between 2013 and 2015. With limited understanding of the potential for human-to-human transmission, it was difficult to implement control measures efficiently or to inform the public adequately about the application of interventions. In this study, the human-to-human transmission rate for the epidemics that occurred between 2013 and 2015 in Zhejiang Province, China, was analysed. The reproduction number (R), a key indicator of transmission intensity, was estimated by fitting the number of infections from poultry to humans and from humans to humans into a mathematical model. The posterior mean R for human-to-human transmission was estimated to be 0·27, with a 95% credible interval of 0·14-0·44 for the first wave, whereas the posterior mean Rs decreased to 0·15 in the second and third waves. Overall, these estimates indicate that a human H7N9 pandemic is unlikely to occur in Zhejiang. The reductions in the viral transmissibility and the number of poultry-transmitted infections after the first epidemic may be attributable to the various intervention measures taken, including changes in the extent of closures of live poultry markets.


Assuntos
Transmissão de Doença Infecciosa , Epidemias , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Influenza Humana/transmissão , Influenza Humana/virologia , Número Básico de Reprodução , China/epidemiologia , Humanos , Influenza Humana/epidemiologia , Modelos Teóricos
13.
Genet Mol Res ; 15(2)2016 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-27323013

RESUMO

Recently genome-wide association studies on East Asian populations reported an association between diabetes and several single nucleotide polymorphisms (SNPs) in a 40-kb linkage disequilibrium block in intron 15 of KCNQ1. However, the association between KCNQ1 variants and type 2 diabetes mellitus (T2DM) in Chinese Kazakh populations is unknown. We investigated the relationship between rs2237892 and rs2237895 SNPs in KCNQ1 and susceptibility to and clinical characteristics of T2DM in 100 Chinese Kazakh T2DM subjects and 100 healthy subjects. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism and the main anthropometric and biochemical parameters of individuals were assessed in the genotype groups (rs2237892: CC, CT, or TT, and rs2237895: AA, AC, or CC). Genotype distribution and allele frequencies of these two SNPs were not significantly different between T2DM and control groups (P > 0.05). The frequencies of CT and TT genotypes and T allele for the rs2237892 SNP in females with T2DM were significantly higher than that in the control group (genotype: P = 0.016, allele: P = 0.004). However, there were no significant differences among individuals with different genotypes with respect to the rs2237895 SNP (P > 0.05). The main anthropometric and biochemical parameters did not correlate with the rs2237892 or rs2237895 SNPs in the T2DM group (P > 0.05). Thus, the T allele-containing genotypes of the rs2237892 SNP in KCNQ1 may increase the susceptibility to T2DM in female Chinese Kazakh individuals, whereas the rs2237895 SNP may not be associated with T2DM in the Chinese Kazakh population.


Assuntos
Canal de Potássio KCNQ1/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Diabetes Mellitus Tipo 2/genética , Etnicidade/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genética Populacional , Humanos , Canal de Potássio KCNQ1/metabolismo , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
14.
Br J Cancer ; 112(8): 1326-31, 2015 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-25867272

RESUMO

BACKGROUND: Simultaneous chemotherapy with vascular endothelial growth factor (VEGF) inhibition has not shown additional benefit over chemotherapy alone in advanced melanoma. We tested administration of the potent VEGF inhibitor axitinib followed by paclitaxel/carboplatin to determine whether enhanced tumour proliferation during axitinib withdrawal leads to sustained chemosensitivity. METHODS: We conducted a prospective phase II trial in metastatic melanoma patients with ECOG performance status 0-1 and normal organ function. Axitinib 5 mg PO b.i.d. was taken on days 1-14 of each 21-day treatment cycle, and carboplatin (AUC=5) with paclitaxel (175 mg m(-2)) was administered on day 1 starting with cycle 2. 3'-Deoxy-3'-(18)F-fluorothymidine ((18)F-FLT)-PET scans were performed in five patients to assess tumour proliferation on days 1, 14, 17, and 20 of cycle 1. Molecular profiling for BRAF was performed for all patients with cutaneous, acral, or mucosal melanoma. RESULTS: The treatment was well tolerated. The most common grade 3 AEs were hypertension, neutropenia, and anaemia. Grade 4 non-haematologic AEs were not observed. Four of five patients completing (18)F-FLT-PET scans showed increases (23-92%) in SUV values during the axitinib holiday. Of 36 evaluable patients, there were 8 confirmed PRs by Response Evaluation Criteria in Solid Tumors. Overall, 20 patients had SD and 8 had PD as the best response. The median PFS was 8.7 months and the median overall survival was 14.0 months. Five BRAF(V600E/K) patients had significantly worse PFS than patients without these mutations. CONCLUSIONS: Axitinib followed by carboplatin and paclitaxel was well tolerated and effective in BRAF wild-type metastatic melanoma. 3'-Deoxy-3'-(18)F-fluorothymidine-PET scans showed increased proliferation during axitinib withdrawal.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imidazóis/administração & dosagem , Indazóis/administração & dosagem , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Axitinibe , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Didesoxinucleosídeos , Feminino , Humanos , Imidazóis/efeitos adversos , Indazóis/efeitos adversos , Masculino , Melanoma/diagnóstico por imagem , Melanoma/genética , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Tomografia por Emissão de Pósitrons/métodos , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Radiografia , Resultado do Tratamento
15.
Ultrasound Obstet Gynecol ; 46(4): 478-86, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25846569

RESUMO

OBJECTIVES: To determine the frequency of clinically significant chromosomal abnormalities identified by chromosomal microarray in pregnancy losses at any gestational age and to compare microarray performance with that of traditional cytogenetic analysis when testing pregnancy losses. METHODS: Among 535 fetal demise specimens of any gestational age, clinical microarray-based comparative genomic hybridization (aCGH) was performed successfully on 515, and a subset of 107 specimens underwent additional single nucleotide polymorphism (SNP) analysis. RESULTS: Overall, clinically significant abnormalities were identified in 12.8% (64/499) of specimens referred with normal or unknown karyotypes. Detection rates were significantly higher with earlier gestational age. In the subset with normal karyotype, clinically significant abnormalities were identified in 6.9% (20/288). This detection rate did not vary significantly with gestational age, suggesting that, unlike aneuploidy, the contribution of submicroscopic chromosomal abnormalities to fetal demise does not vary with gestational age. In the 107 specimens that underwent aCGH and SNP analysis, seven cases (6.5%) had abnormalities of potential clinical significance detected by the SNP component, including female triploidy. aCGH failed to yield fetal results in 8.3%, which is an improvement over traditional cytogenetic analysis of fetal demise specimens. CONCLUSIONS: Both the provision of results in cases in which karyotype fails and the detection of abnormalities in the presence of a normal karyotype demonstrate the increased diagnostic utility of microarray in pregnancy loss. Thus, chromosomal microarray testing is a preferable, robust method of analyzing cases of pregnancy loss to better delineate possible genetic etiologies, regardless of gestational age.


Assuntos
Aborto Espontâneo/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Natimorto/genética , Aneuploidia , Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Transtornos Cromossômicos/genética , Hibridização Genômica Comparativa/métodos , Análise Citogenética/métodos , Feminino , Feto , Humanos , Cariotipagem/métodos , Masculino , Polimorfismo de Nucleotídeo Único , Gravidez , Diagnóstico Pré-Natal/métodos , Triploidia
16.
Med J Malaysia ; 70(2): 86-92, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26162383

RESUMO

INTRODUCTION: Cardiovascular diseases are the main cause of morbidity and mortality in Malaysia. There is evidence of high traditional and complementary medicine (TCM) use among population with cardiovascular risk and there have been anecdotal reports about substitution of conventional medicines with TCM. We investigated the prevalence of TCM use, treatment preference and substitution of conventional medicines in study population with cardiovascular risk factors in Pahang, Malaysia. METHODS: A cross-sectional survey was conducted using an interviewer-administered questionnaire in five districts of Pahang. A total of 1250 households were chosen through proportionate and systematic sampling. Respondents aged 18 years and above were selected. RESULTS: The study population with cardiovascular risk factors who used TCM was higher than the general population (31.7% versus 25.9%). There were no clear preferences in using TCM by gender, age groups, educational level and income even though other bumiputeras showed a slight inclination towards TCM use. Among the study population with cardiovascular risk factors who consumed TCM, 20-30% of them were using TCM as a substitute for their conventional medications. Respondents from the younger age group (18-40 years) (57.1%), highest educational level (43.2%), other bumiputeras (38.4%) and highest income group (31.4%) preferred the combination of both conventional and traditional medicine. CONCLUSION: TCM use among population with cardiovascular risk factors is high. The high preference for combination therapy of TCM and conventional medications among young adults and the use of TCM to substitute conventional medications show that much research is needed to provide proven TCM therapies to avoid self-mismanagement of cardiovascular risk in Malaysia.

17.
Epidemiol Infect ; 142(5): 955-63, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24107289

RESUMO

During the surveillance of influenza pandemics, underreported data are a public health challenge that complicates the understanding of pandemic threats and can undermine mitigation efforts. We propose a method to estimate incidence reporting rates at early stages of new influenza pandemics using 2009 pandemic H1N1 as an example. Routine surveillance data and statistics of travellers arriving from Mexico were used. Our method incorporates changes in reporting rates such as linearly increasing trends due to the enhanced surveillance. From our results, the reporting rate was estimated at 0·46% during early stages of the pandemic in Mexico. We estimated cumulative incidence in the Mexican population to be 0·7% compared to 0·003% reported by officials in Mexico at the end of April. This method could be useful in estimation of actual cases during new influenza pandemics for policy makers to better determine appropriate control measures.


Assuntos
Métodos Epidemiológicos , Influenza Humana/epidemiologia , Pandemias/estatística & dados numéricos , Viagem/estatística & dados numéricos , Humanos , Vírus da Influenza A Subtipo H1N1 , México/epidemiologia , Modelos Biológicos
18.
Prenat Diagn ; 34(2): 163-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24218399

RESUMO

OBJECTIVES: Cornelia de Lange syndrome (CdLS) is characterized by distinct facial features, growth retardation, upper limb reduction defects, hirsutism, and intellectual disability. NIPBL mutations have been identified in approximately 60% of patients with CdLS diagnosed postnatally. Prenatal ultrasound findings include upper limb reduction defects, intrauterine growth restriction, and micrognathia. CdLS has also been associated with decreased PAPP-A and increased nuchal translucency (NT). We reviewed NIPBL sequence analysis results for 12 prenatal samples in our laboratory to determine the frequency of mutations in our cohort. METHODS: This retrospective study analyzed data from all 12 prenatal cases with suspected CdLS, which were received by The University of Chicago Genetic Services Laboratories. Diagnostic NIPBL sequencing was performed for all samples. Clinical information was collected from referring physicians. RESULTS: NIPBL mutations were identified in 9 out of the 12 cases prenatally (75%). Amongst the NIPBL mutation-positive cases with clinical information available, the most common findings were upper limb malformations and micrognathia. Five patients had NT measurements in the first trimester, of which four were noted to be increased. CONCLUSION: We demonstrate that prenatally-detected phenotypes of CdLS, particularly severe micrognathia and bilateral upper limb defects, are associated with an increased frequency of NIPBL mutations.


Assuntos
Síndrome de Cornélia de Lange/genética , Micrognatismo/diagnóstico por imagem , Proteínas/genética , Deformidades Congênitas das Extremidades Superiores/diagnóstico por imagem , Proteínas de Ciclo Celular , Estudos de Coortes , Síndrome de Cornélia de Lange/complicações , Síndrome de Cornélia de Lange/diagnóstico por imagem , Feminino , Humanos , Recém-Nascido , Micrognatismo/etiologia , Mutação , Medição da Translucência Nucal , Gravidez , Diagnóstico Pré-Natal , Estudos Retrospectivos , Análise de Sequência de DNA , Ultrassonografia Pré-Natal , Deformidades Congênitas das Extremidades Superiores/etiologia
20.
Diabet Med ; 30(4): e127-34, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23278432

RESUMO

AIM: To assess factors influencing glycaemic control following gastric bypass surgery in patients with Type 2 diabetes and BMI< 30 kg/m(2) . METHODS: Prospective longitudinal study of 103 patients with inadequate glycaemic control who underwent gastric bypass surgery at Soonchunhyang University, Seoul, Korea (n = 66) and Min-Sheng General Hospital, Taipei, Taiwan (n = 37). Procedures were performed August 2009 to January 2011. Key outcome measures were excellent glycaemic control of Type 2 diabetes defined as HbA1c < 42 mmol/mol (≤6%); inadequate response defined as HbA1c > 53 mmol/mol (> 7%). Analysis was conducted using binary logistic regression, and cut-points obtained from receiver operator characteristics. RESULTS: Excellent glycaemic control was achieved in 31 (30%) at 1 year. Diabetes duration of < 7 years and BMI > 27 kg/m(2) provided independent predictors and useful cut-points. Likelihood of excellent glycaemic control for an individual could be estimated using loge (Odds) = -6.7 + (0.26 × BMI) + (-1.2 × diabetes duration). Baseline BMI of < 27 kg/m(2) and baseline C-peptide of < 2.0ng/ml, best predicted a poor glycaemic response. In those with favourable baseline characteristics percentage weight loss (%WL) had a dominant influence on glycaemic outcomes. Baseline C-peptide (> 2.4 ng/ml) and subsequent percentage weight loss (> 16%) were associated with excellent glycaemic control. Higher BMI was associated with greater percentage weight loss. CONCLUSION: In patients with Type 2 diabetes and BMI < 30 kg/m(2) , glycaemic response to gastric bypass is predicted by higher baseline BMI, shorter disease duration and higher fasting C-peptide. Post-surgery weight loss has a dominant effect. Baseline BMI and weight loss have a major influence on outcomes.


Assuntos
Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica/métodos , Laparoscopia/métodos , Redução de Peso/fisiologia , Adulto , Idoso , Glicemia/metabolismo , Índice de Massa Corporal , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 2/sangue , Jejum/sangue , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
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