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1.
Clin Oncol (R Coll Radiol) ; 36(2): e87-e96, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38114358

RESUMO

AIMS: Many recent studies related to cancer surgery have reported that sarcopenia influences mortality in surgical patients. However, few comprehensive studies have examined the associations between sarcopenia and short- and long-term surgical outcomes of metastatic cancer, especially breast cancer with brain metastasis. In the present study, we investigated the association between sarcopenia and mortality in patients who underwent gamma knife radiosurgery (GKRS) for brain metastasis with breast cancer. MATERIALS AND METHODS: This retrospective study analysed 157 patients who underwent GKRS for brain metastasis with breast cancer between January 2014 and December 2018. A Cox regression analysis was carried out to evaluate the association between sarcopenia and mortality at 90 days, 180 days, 1 year, 3 years and the overall period. RESULTS: In the Cox regression analysis, sarcopenia was significantly associated with high 90-day mortality (adjusted hazard ratio 3.46, 95% confidence interval 1.24-9.67, P = 0.018), 180-day mortality (adjusted hazard ratio 2.67, 95% confidence interval 1.37-5.22, P = 0.004), 1-year mortality (adjusted hazard ratio 2.39, 95% confidence interval 1.42-4.02, P = 0.001), 3-year mortality (adjusted hazard ratio 2.39, 95% confidence interval 1.53-3.74, P < 0.001) and overall mortality (adjusted hazard ratio 2.11, 95% confidence interval 1.37-3.26, P < 0.001). CONCLUSION: Sarcopenia could be a risk factor for short- and long-term mortality in patients undergoing GKRS for brain metastasis from breast cancer.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Radiocirurgia , Sarcopenia , Humanos , Feminino , Radiocirurgia/efeitos adversos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Resultado do Tratamento , Estudos Retrospectivos , Sarcopenia/complicações , Sarcopenia/cirurgia , Estudos de Coortes , Neoplasias Encefálicas/secundário
2.
Osteoporos Int ; 34(12): 2027-2045, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37566158

RESUMO

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.


Assuntos
Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Masculino , Humanos , Feminino , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/complicações , Osteoporose/complicações , Fraturas do Quadril/etiologia , Fraturas do Quadril/complicações , Densidade Óssea , Fatores de Risco , Medição de Risco
3.
Osteoporos Int ; 33(10): 2103-2136, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35639106

RESUMO

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).


Assuntos
Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Densidade Óssea , Fraturas do Quadril/complicações , Fraturas do Quadril/etiologia , Humanos , Osteoporose/complicações , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
4.
Artigo em Inglês | MEDLINE | ID: mdl-34007909

RESUMO

BACKGROUND: The exploration of Advanced Practiced Radiation Therapists (APRTs) development in Singapore started in 2011. This study aims to provide an overview of the development of the APRT roles, and to discuss the approaches used to develop and implement these roles in Singapore. MATERIALS AND METHODS: A mixed methods approach was used in the development of the APRT program. A literature review was carried out to define the APRT scope of practice and core responsibilities. A competency and assessment framework were setup to assess the core competency areas. With this framework, a structured 1-year residency training program was developed. RESULTS: The scope of practice and core responsibilities of APRTs were defined with five proposed advanced practice profiles being successfully validated. A competency framework was set up to assess the core competency domains: clinical, technical and professional competencies, research, education and leadership. A 4-point scoring system was developed for the competency assessment based on two criteria; the frequency with which RTTs would demonstrate competency, and the ability of performing the task competently. A 1-year structured APRT residency program was developed and implemented. The programme consisted of structured lectures, and clinical practice-based modules where APRT residents receive structured mentoring under a mentorship program. CONCLUSION: The APRT program in Singapore employed an evidence-based implementation process that tested the feasibility of a new practice model. Multidisciplinary involvements, mentorship and clinical training were important factors for the success of the APRT program.

5.
Int J Tuberc Lung Dis ; 25(1): 31-35, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33384042

RESUMO

BACKGROUND: Adipokines are emerging mediators of immune response, and may affect susceptibility to active TB.OBJECTIVE: To examine the associations between adipokines and the risk of active TB.METHODS: In a case-control study nested within a prospective cohort of middle-aged and older adults in Singapore, 280 incident active TB cases who donated blood for research before diagnosis were matched with 280 controls. Serum levels of adiponectin, resistin, leptin and ghrelin were measured. Multivariable logistic regression models were used to compute the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between adipokines and the risk of active TB.RESULTS: Higher levels of leptin and resistin were associated with reduced risk of TB in a dose-dependent manner. Compared to those in the lowest quartile of leptin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.26-0.82; P for trend = 0.009). Similarly, compared to those in the lowest quartile of resistin levels, those in the highest quartile had an OR of 0.46 (95%CI 0.24-0.90; P for trend = 0.03). Adiponectin and ghrelin levels were not associated with TB risk.CONCLUSION: Increased serum levels of leptin and resistin may be associated with reduced susceptibility to active TB infection.


Assuntos
Adipocinas/sangue , Tuberculose/sangue , Adiponectina , Idoso , Estudos de Casos e Controles , Grelina , Humanos , Leptina , Pessoa de Meia-Idade , Estudos Prospectivos , Resistina , Fatores de Risco , Singapura
7.
J Nutr Health Aging ; 24(4): 371-378, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32242204

RESUMO

OBJECTIVES: Asian studies on how physical tests predict short-term mortality in elderly are scarce. We assessed handgrip strength and timed-up-and-go (TUG) as such predictors among elderly Chinese in Singapore. DESIGN: Prospective cohort study. SETTING: Community-dwelling Chinese elderly in Singapore. PARTICIPANTS: We used data from 13,789 subjects in the prospective, population-based Singapore Chinese Health Study, who had a mean age of 74 (range 63 to 97) years at time of measurements. MEASUREMENTS: Subjects underwent assessment for handgrip strength and TUG. They were followed for mortality via linkage with nationwide death registry through 2018. RESULTS: In multivariable analyses, handgrip strength was inversely associated with risk of mortality in a dose-dependent manner: the hazard ratio (HR) [95% confidence interval (CI)] comparing extreme quartiles was 2.05 (1.44-2.90) (Ptrend<0.001). TUG was positively associated with mortality in a stepwise manner: the HR (95% CI) comparing extreme quartiles was 3.08 (2.17-4.38) (Ptrend<0.001). Compared to those with stronger handgrip and faster TUG, participants who either had weaker handgrip or slower TUG had a significant 1.59 to 2.11 fold increase in risk of mortality; while the HR (95% CI) for those who had both weaker handgrip and slower TUG was 3.93 (3.06-5.05). In time-dependent receiver operating characteristic curves, adding handgrip strength and TUG time to a Cox model containing sociodemographic and lifestyle factors, comorbidities, and body measurements significantly improved the area under the curve for the prediction of mortality from 0.5 to 2 years (P≤0.001). CONCLUSION: Among elderly in a Chinese population, handgrip strength and TUG test were strong and independent predictors of short-term mortality.


Assuntos
Força da Mão/fisiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Prospectivos , Singapura
9.
J Econ Ageing ; 142019.
Artigo em Inglês | MEDLINE | ID: mdl-31857943

RESUMO

Singapore is one of the fastest-aging populations due to increased life expectancy and lowered fertility. Lifestyle changes increase the burden of chronic diseases and disability. These have important implications for social protection systems. The goal of this paper is to model future functional disability and healthcare expenditures based on current trends. To project the health, disability and hospitalization spending of future elders, we adapted the Future Elderly Model (FEM) to Singapore. The FEM is a dynamic Markov microsimulation model developed in the US. Our main source of population data was the Singapore Chinese Health Study (SCHS) consisting of 63,000 respondents followed up over three waves from 1993 to 2010. The FEM model enables us to investigate the effects of disability compounded over the lifecycle and hospitalization spending, while adjusting for competing risk of multi-comorbidities. Results indicate that by 2050, 1 in 6 elders in Singapore will have at least one ADL disability and 1 in 3 elders will have at least one IADL disability, an increase from 1 in 12 elders and 1 in 5 elders respectively in 2014. The highest prevalence of functional disability will be in those aged 85 years and above. Lifetime hospitalization spending of elders aged 55 and above is US$24,400 (30.2%) higher among people with functional disability compared to those without disability. Policies that successfully tackle diabetes and promote healthy living may reduce or delay the onset of disability, leading to potential saving. In addition, further technological improvements may reduce the financial burden of disability.

11.
Osteoarthritis Cartilage ; 27(8): 1129-1137, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30902701

RESUMO

OBJECTIVES: Knee osteoarthritis (OA) is more common in women, and may be related to reproductive or hormonal factors. We evaluated these factors with the risk of total knee replacement (TKR) for severe knee OA among women. METHODS: The Singapore Chinese Health Study recruited 63,257 Chinese aged 45-74 years from 1993 to 1998, and among them, 35,298 were women. Information on height, weight, lifestyle factors, number of biological children, ages at menarche and menopause, and use of hormonal therapies was collected through interviews. Incident cases of TKR were identified via linkage with nationwide database. RESULTS: There were 1,645 women with TKR after mean follow-up of 14.8 years. Higher parity was associated with increased TKR risk in a stepwise manner (P for trend <0.001). Compared to nulliparous women, those with ≥5 children had the highest risk [hazard ratio (HR) 2.01, 95% confidence intervals (CIs) 1.50-2.70]. The effect of parity on TKR risk was significantly stronger among lean women compared to heavier women; HRs (95% CIs) for highest parity was 4.86 (2.22-10.63) for women with body mass index (BMI) <23 kg/m2 and 1.57 (1.14-2.14) for those ≥23 kg/m2 (P for interaction = 0.001). Earlier age at menarche and use of oral contraceptives were significantly associated with TKR in a stepwise manner (P for trend ≤0.002). Age at menopause and use of hormonal therapy were not associated with TKR risk. CONCLUSION: Higher parity, earlier age of menarche and use of oral contraceptives were associated with increased risk of TKR for severe knee OA among women.


Assuntos
Artroplastia do Joelho/estatística & dados numéricos , Osteoartrite do Joelho/cirurgia , História Reprodutiva , Idoso , Índice de Massa Corporal , Estudos de Coortes , Anticoncepcionais Orais , Feminino , Seguimentos , Humanos , Menarca , Pessoa de Meia-Idade , Osteoartrite do Joelho/epidemiologia , Paridade , Singapura/epidemiologia
12.
Ann Oncol ; 30(3): 478-485, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698666

RESUMO

BACKGROUND: Increased vitamin B6 catabolism related to inflammation, as measured by the PAr index (the ratio of 4-pyridoxic acid over the sum of pyridoxal and pyridoxal-5'-phosphate), has been positively associated with lung cancer risk in two prospective European studies. However, the extent to which this association translates to more diverse populations is not known. MATERIALS AND METHODS: For this study, we included 5323 incident lung cancer cases and 5323 controls individually matched by age, sex, and smoking status within each of 20 prospective cohorts from the Lung Cancer Cohort Consortium. Cohort-specific odds ratios (ORs) and 95% confidence intervals (CIs) for the association between PAr and lung cancer risk were calculated using conditional logistic regression and pooled using random-effects models. RESULTS: PAr was positively associated with lung cancer risk in a dose-response fashion. Comparing the fourth versus first quartiles of PAr resulted in an OR of 1.38 (95% CI: 1.19-1.59) for overall lung cancer risk. The association between PAr and lung cancer risk was most prominent in former smokers (OR: 1.69, 95% CI: 1.36-2.10), men (OR: 1.60, 95% CI: 1.28-2.00), and for cancers diagnosed within 3 years of blood draw (OR: 1.73, 95% CI: 1.34-2.23). CONCLUSION: Based on pre-diagnostic data from 20 cohorts across 4 continents, this study confirms that increased vitamin B6 catabolism related to inflammation and immune activation is associated with a higher risk of developing lung cancer. Moreover, PAr may be a pre-diagnostic marker of lung cancer rather than a causal factor.


Assuntos
Inflamação/sangue , Neoplasias Pulmonares/sangue , Metabolismo , Vitamina B 6/sangue , Adulto , Idoso , Feminino , Humanos , Inflamação/patologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Ácido Piridóxico/metabolismo , Fatores de Risco , Fumantes
13.
Int J Tuberc Lung Dis ; 23(12): 1277-1282, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31931911

RESUMO

SETTING: Although diabetes (DM) and low body mass index (BMI) are established risk factors for active tuberculosis (TB), the joint effect of type 2 diabetes (T2D) and BMI is unclear.DESIGN: A prospective cohort of 63,257 adults aged 45-74 years were recruited from 1993 to 1998 in Singapore. Active TB cases were identified via linkage with the National TB Registry up to December 2014. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the relations of T2D and BMI, independently and jointly, with TB risk.RESULTS: T2D was associated with increased TB risk (HR 2.31, 95% CI 1.93-2.78). Conversely, BMI was inversely associated with TB risk: HR for underweight (BMI < 18.5 kg/m²) was 2.87 (95% CI 2.15-3.82) compared to obese (BMI ≥ 27.5 kg/m²) individuals. Compared to obese individuals without T2D, HR for active TB among underweight individuals with T2D was 8.30 (95% CI 4.43-15.54). There was no statistically significant interaction between BMI and T2D on TB risk (Pinteraction = 0.85).CONCLUSION: Underweight and T2D are independent determinants for active TB. This has important public health implications in Asia where prevalence of tuberculous infection is high, and T2D occurs at lower levels of BMI.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Tuberculose Pulmonar/epidemiologia , Idoso , Índice de Massa Corporal , Estudos de Coortes , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Singapura/epidemiologia , Tuberculose Pulmonar/complicações
14.
Ann Oncol ; 29(6): 1468-1475, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29617726

RESUMO

Background: There is observational evidence suggesting that high vitamin D concentrations may protect against lung cancer. To investigate this hypothesis in detail, we measured circulating vitamin D concentrations in prediagnostic blood from 20 cohorts participating in the Lung Cancer Cohort Consortium (LC3). Patients and methods: The study included 5313 lung cancer cases and 5313 controls. Blood samples for the cases were collected, on average, 5 years before lung cancer diagnosis. Controls were individually matched to the cases by cohort, sex, age, race/ethnicity, date of blood collection, and smoking status in five categories. Liquid chromatography coupled with tandem mass spectrometry was used to separately analyze 25-hydroxyvitamin D2 [25(OH)D2] and 25-hydroxyvitamin D3 [25(OH)D3] and their concentrations were combined to give an overall measure of 25(OH)D. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for 25(OH)D as both continuous and categorical variables. Results: Overall, no apparent association between 25(OH)D and risk of lung cancer was observed (multivariable adjusted OR for a doubling in concentration: 0.98, 95% CI: 0.91, 1.06). Similarly, we found no clear evidence of interaction by cohort, sex, age, smoking status, or histology. Conclusion: This study did not support an association between vitamin D concentrations and lung cancer risk.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/epidemiologia , Neoplasias Pulmonares/epidemiologia , Carcinoma de Pequenas Células do Pulmão/epidemiologia , Deficiência de Vitamina D/fisiopatologia , Vitamina D/sangue , Adenocarcinoma/sangue , Adenocarcinoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Grandes/sangue , Carcinoma de Células Grandes/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Saúde Global , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Carcinoma de Pequenas Células do Pulmão/sangue , Vitaminas/sangue , Adulto Jovem
15.
Osteoarthritis Cartilage ; 25(12): 1962-1968, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28757187

RESUMO

OBJECTIVE: While cross-sectional and retrospective case-control studies suggest that gout is associated with knee osteoarthritis (KOA), no prospective study has evaluated the risk of total knee replacement (TKR) for KOA in association with gout. We prospectively evaluated the association between gout and the risk of TKR due to severe KOA. DESIGN: We used data from the Singapore Chinese Health Study (SCHS), a prospective cohort with 63,257 Chinese adults aged 45-74 years at recruitment (1993-1998). Self-report of physician-diagnosed gout was enquired at follow-up I interview (1999-2004) from 52,322 subjects. TKR cases for KOA after follow-up I were identified via linkage with nationwide hospital discharge database through 31 December 2011. Multivariable Cox proportional hazards regression model was applied with adjustment for potential risk factors of KOA. RESULTS: Among 51,858 subjects (22,180 men and 29,678 women) included in this analysis, after average 9.7 follow-up years, there were 1,435 cases of TKR. Gout was associated with 39% higher risk of TKR in women [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.08-1.79] but not in men (HR 0.78; 95% CI 0.49-1.23). The positive gout-TKR association in women remained after excluding participants with self-reported history of arthritis (HR 1.57; 95% CI 1.04-2.37). This association was stronger in women who were lean (body mass index [BMI] < 23 kg/m2) (HR 2.17; 95% CI 1.30-3.64) compared to their heavier counterparts (Pinteraction = 0.016). CONCLUSION: Gout is associated with risk of severe KOA, especially in lean women, suggesting the crystal arthritis may play a role in the pathogenesis or progression of OA.


Assuntos
Artroplastia do Joelho/estatística & dados numéricos , Gota/epidemiologia , Osteoartrite do Joelho/cirurgia , Idoso , Povo Asiático , Índice de Massa Corporal , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Armazenamento e Recuperação da Informação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Osteoartrite do Joelho/epidemiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Singapura/epidemiologia
16.
Int J Tuberc Lung Dis ; 21(7): 818-824, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28633708

RESUMO

SETTING: Tertiary referral centre, Samsung Medical Center, South Korea. OBJECTIVE: To evaluate the pharmacokinetic parameters and toxicities of once-daily amikacin (AMK) dosing for lung disease due to Mycobacterium abscessus. DESIGN: A retrospective review of 48 patients with M. abscessus lung disease who received once-daily AMK for 4 weeks between January 2012 and June 2015. RESULTS: With a starting dose of 15 mg/kg/day and adjustment of AMK dose according to the peak serum level (Cmax), the Cmax target of 55-65 µg/ml was achieved in 31.3% (15/48) of patients in the first week, 68.8% (33/48) in week 2, 91.7% (44/48) in week 3 and 95.8% (46/48) in week 4. Transient nephrotoxicity developed in 6.3% (3/48) of patients and ototoxicity in 25.0% (6/24), which was determined by audiogram as hearing loss, asymptomatic in five patients and tinnitus in one. Multivariate analysis revealed that the highest drug concentration 12 h after administration was significantly associated with the development of toxicities (adjusted odds ratio 1.862, P = 0.047). CONCLUSION: Our results suggest that once-daily AMK for 4 weeks with a target Cmax of 55-65 µg/ml can be used in patients with M. abscessus lung disease, with careful monitoring of toxicity.


Assuntos
Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Mycobacterium abscessus/isolamento & purificação , Idoso , Amicacina/efeitos adversos , Amicacina/farmacocinética , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Feminino , Perda Auditiva/induzido quimicamente , Perda Auditiva/epidemiologia , Humanos , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infecções por Mycobacterium não Tuberculosas/microbiologia , República da Coreia , Estudos Retrospectivos , Zumbido/induzido quimicamente , Zumbido/epidemiologia
17.
Diabet Med ; 34(8): 1145-1153, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28370329

RESUMO

AIM: To gain insight into the presence of islet cell autoimmunity in an ethnic Asian compared with a white European population. METHODS: For this cross-sectional study we recruited people with adult-onset diabetes (age of diagnosis 20-60 years), at tertiary referral centres in Germany (n=1020) and Singapore (n=1088). Glutamic acid decarboxylase and islet antigen 2 antibodies were measured according to Islet Autoantibody Standardization Program protocols. RESULTS: The prevalence of glutamic acid decarboxylase antibody positivity was 13.9% (95% CI 12.1-16.0; P<0.001) in the white European cohort compared with 6.8% (95% CI 5.5-8.4; P<0.001) in the Asian cohort. Glutamic acid decarboxylase antibody positivity was 11.4% (95% CI 7.7-16.6) in Indian, 6.0% (95% CI 3.6-9.9) in Malay and 5.8% (95% CI 4.3-7.7; P<0.001) in Chinese participants. In the white European participants, the prevalence of islet antigen 2 antibody positivity was 7.8% (95% CI 6.4-9.4) compared with 14.8% (95% CI 12.8-17.0; P<0.001) in the Asian cohort as a whole, and among the three ethnicities in the Asian cohort it was 12.4% (95% CI 8.6-17.7) in Indian, 16.8% (95% CI 12.6-22.2) in Malay and 15.7% (95% CI 13.2-18.6) in Chinese participants. Double antibody positivity was seen in 5.7% (95% CI 4.5-7.1) of white European participants compared with 1.6% (95% CI 1.0-2.5; P<0.01) of Asian participants. In the white European cohort, those who were glutamic acid decarboxylase autoantibody-positive had a lower BMI than those who were autoantibody-negative, but this trend was absent in the Asian cohort. CONCLUSIONS: A marked prevalence of islet cell autoimmunity was observed in people with adult-onset diabetes. While glutamic acid decarboxylase antibodies were more frequent in the European cohort, islet antigen 2 antibody positivity was highest in the three ethnic groups in Singapore, suggesting ethnic-specific differences in antibody profiles.


Assuntos
Autoanticorpos/análise , Doenças Autoimunes/imunologia , Autoimunidade , Diabetes Mellitus Tipo 2/imunologia , Glutamato Descarboxilase/antagonistas & inibidores , Proteínas Tirosina Fosfatases Classe 8 Semelhantes a Receptores/antagonistas & inibidores , Adulto , Povo Asiático , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/etnologia , Biomarcadores/sangue , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etnologia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Encaminhamento e Consulta , Singapura/epidemiologia , Centros de Atenção Terciária , População Branca , Adulto Jovem
18.
Int J Tuberc Lung Dis ; 21(3): 345-350, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28225347

RESUMO

OBJECTIVE: To evaluate the proportion and clinical characteristics of patients with non-tuberculous mycobacteria (NTM) lung disease diagnosed based on positive culture results in liquid medium only. METHODS: We reviewed the medical records of 978 patients diagnosed with NTM lung disease. All clinical samples were cultured in both solid and liquid media. RESULTS: Of the 978 patients, 111 (11.3%) were culture-positive in liquid medium only (liquid culture group), and 867 (88.7%) (solid culture group) on solid medium, regardless of the culture results in liquid medium. At the time of diagnosis, the liquid culture group was less likely than the solid culture group to have haemoptysis (11.7% vs. 20.0%, P = 0.04), positive sputum smear for acid-fast bacilli (14.4% vs. 50.2%, P < 0.001) or the fibrocavitary form of NTM lung disease (3.6% vs. 14.6%, P = 0.001). During the median follow-up period of 28.9 months (interquartile range 19.1-41.6), the proportion of patients requiring antibiotic treatment was lower in the liquid culture group than in the solid culture group (44.1% vs. 61.6%, P < 0.001). CONCLUSIONS: Liquid media culture is helpful in the diagnosis of patients with less severe forms of NTM lung disease.


Assuntos
Pneumopatias/diagnóstico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Micobactérias não Tuberculosas/isolamento & purificação , Escarro/microbiologia , Idoso , Meios de Cultura , Feminino , Humanos , Pneumopatias/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/microbiologia , Índice de Gravidade de Doença
19.
Int J Tuberc Lung Dis ; 21(1): 100-106, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28157472

RESUMO

SETTING: Citation analyses aid in assessing quality, trends and future directions of research fields. OBJECTIVE: To identify the most influential articles on infections caused by non-tuberculous mycobacteria (NTM) in the last 20 years. DESIGN: We performed a cited reference search of the Web of Science database from 1995 to 2015. The 100 most cited articles on NTM infections were analysed. RESULTS: The top 100 articles were cited 114-1471 times, and were published from 1995 to 2013. Sixty-five were laboratory-based, basic science articles, with the major topics being pathophysiology (n = 20) and molecular methods for NTM identification (n = 15). Among the 35 non-laboratory studies, major topics were clinical management (n = 15) and epidemiology (n = 14). The top article was a clinical treatise on the management of NTM disease, published in 2007. Although there was a correlation between article rank and journal impact factor (P = 0.043, ρ = -0.202), the five articles from the journals with highest impact factors did not rank among the top 10 articles. CONCLUSION: A large proportion of influential articles on NTM infection are basic scientific studies, and the most influential articles are not always published in high-impact journals.


Assuntos
Bibliometria , Infecções por Mycobacterium não Tuberculosas , Publicações Periódicas como Assunto/tendências , Humanos , Fator de Impacto de Revistas
20.
Int J Tuberc Lung Dis ; 20(12): 1594-1602, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27931333

RESUMO

BACKGROUND: Little information is available regarding vitamin D-associated factors in patients with non-tuberculous mycobacteria (NTM) lung disease. OBJECTIVE: To determine the association between vitamin D-related factors and susceptibility to NTM lung disease. DESIGN: The relative gene expression levels of cathelicidin (CAMP), defensin (DEFB4), vitamin D receptor (VDR) and 1-hydroxylase (CYP27B1), as well as the serum levels of 25-hydroxyvitamin D (25[OH]D), cathelicidin (LL-37), defensin (hBD-2) and vitamin D-binding protein (DBP) from 82 patients with NTM lung disease and 28 control subjects were analysed. RESULTS: Gene expression of CAMP and DEFB4 was significantly higher, and gene expression of VDR and CYP27B1 was significantly lower, in NTM patients than controls. Serum LL-37 and hBD-2 levels were not significantly different between NTM patients and controls; however, the serum DBP level was higher in NTM patients than controls. The serum vitamin D status of patients did not correlate with serum LL-37, hBD-2, or DBP concentration or gene expression of CAMP, DEFB4, VDR or CYP27B1. CONCLUSION: A higher level of gene expression for antimicrobial peptide is more likely to be associated with NTM lung disease than serum vitamin D status.


Assuntos
Infecções por Mycobacterium não Tuberculosas/sangue , Deficiência de Vitamina D/epidemiologia , Vitamina D/sangue , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/genética , 25-Hidroxivitamina D3 1-alfa-Hidroxilase/metabolismo , Idoso , Peptídeos Catiônicos Antimicrobianos/sangue , Estudos de Casos e Controles , Catelicidinas/genética , Catelicidinas/metabolismo , Linhagem Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/complicações , Micobactérias não Tuberculosas/isolamento & purificação , Prevalência , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , República da Coreia/epidemiologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/complicações , beta-Defensinas/genética , beta-Defensinas/metabolismo
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