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1.
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
2.
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
3.
Osteoporos Int ; 32(6): 1217-1219, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33903925

RESUMO

In patients with surgical repair of a low-trauma hip fracture, zoledronic acid (ZA) reduced the risk of subsequent fractures regardless of pretreatment femoral neck and total hip bone mineral density (BMD). INTRODUCTION: Zoledronic acid reduces the risk of subsequent fractures after repair of a hip fracture. It is still unclear whether the benefits in fracture reduction with ZA depend upon hip bone mineral density at the time of fracture. METHODS: We preformed additional post hoc analyses of data from the HORIZON Recurrent Fracture Trial to determine if ZA treatment reduced the risk of new clinical fractures regardless of pretreatment BMD. We modeled femoral neck and total hip BMD as both continuous and dichotomous variables (BMD T-score above and below -2.5). RESULTS: There are no evidence that baseline femoral neck and total hip BMD modified the anti-fracture efficacy of ZA when pretreatment BMD was analyzed as a continuous or a dichotomous variable (interaction p-values > 0.20). The clinical fracture efficacy of ZA was similar among patients with pretreatment femoral neck BMD values above and below -2.5 (relative hazards = 0.60 and 0.67, respectively, interaction p-value = 0.95). A similar result was obtained using pretreatment total hip BMD values (relative hazards = 0.72 and 0.57, respectively, interaction p-value = 0.41). CONCLUSION: There data should provide more comfort in prescribing ZA after surgical repair of a hip fracture, regardless of pretreatment BMD.


Assuntos
Conservadores da Densidade Óssea , Fraturas do Quadril , Densidade Óssea , Conservadores da Densidade Óssea/uso terapêutico , Colo do Fêmur/cirurgia , Fraturas do Quadril/prevenção & controle , Fraturas do Quadril/cirurgia , Humanos , Ácido Zoledrônico/uso terapêutico
5.
Osteoporos Int ; 32(5): 817-829, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33305343

RESUMO

While many clinical guidelines recommend screening for osteoporosis for early detection and treatment, there is great diversity in the case-finding strategies globally. We sought to compare case-finding strategies, focusing on the approaches used in European and Asian countries. This article provides an overview of the current case-finding strategies in the UK, Germany (including Austria and German-speaking regions of Switzerland), China, Japan, and Korea. We conducted a review of current treatment guidelines in each country and included expert opinions from key opinion leaders. Most countries define osteoporosis among patients with a radiographically identified fracture of the hip or the vertebrae. However, for other types of fractures, or in the absence of a fracture, varying combinations of risk-factor assessment and areal bone mineral density (aBMD) assessed by dual X-ray absorptiometry are used to define osteoporosis cases. A T-score ≤ - 2.5 is accepted to identify osteoporosis in the absence of a fracture; however, not all countries accept DXA alone as the sole criteria. Additionally, the critera for requiring clinical risk factors in addition to aBMD differ across countries. In most Asian countries, aBMD scanning is only provided beyond a particular age threshold. However, all guidelines recommend fracture risk assessment in younger ages if risk factors are present. Our review identified that strategies for case-finding differ regionally, particularly among patients without a fracture. More homogenized ways of identifying osteoporosis cases are needed, in both the Eastern and the Western countries, to improve osteoporosis case-finding before a fracture occurs.Case-finding in osteoporosis is essential to initiate treatment and minimize fracture risk. We identified differences in case-finding strategies between Eastern and Western countries. In the absence of a diagnosed fracture, varying combinations of risk factors and bone density measurements are used. Standardized case-finding strategies may help improve treatment rates.


Assuntos
Osteoporose , Absorciometria de Fóton , Ásia , Áustria , Densidade Óssea , China , Alemanha , Humanos , Japão , Osteoporose/diagnóstico , Osteoporose/epidemiologia , República da Coreia , Suíça
8.
Pharmacogenomics J ; 20(3): 482-493, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31806883

RESUMO

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10-8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy.


Assuntos
Negro ou Afro-Americano/genética , Diuréticos/sangue , Variação Genética/genética , Hipertensão/sangue , Hipertensão/genética , População Branca/genética , Diuréticos/efeitos adversos , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/tratamento farmacológico , Lipídeos/sangue
9.
Pharmacogenomics J ; 18(1): 127-135, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27958378

RESUMO

Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10-8), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.


Assuntos
Eletrocardiografia/efeitos dos fármacos , Etnicidade/genética , Compostos de Sulfonilureia/efeitos adversos , Idoso , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/genética , Citocromo P-450 CYP2C9/genética , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Feminino , Variação Genética/efeitos dos fármacos , Variação Genética/genética , Estudo de Associação Genômica Ampla/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodos , Testes Farmacogenômicos/métodos , Compostos de Sulfonilureia/uso terapêutico
10.
Pharmacogenomics J ; 18(2): 215-226, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28719597

RESUMO

Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.


Assuntos
Envelhecimento/genética , Etnicidade/genética , Genômica/tendências , Frequência Cardíaca/genética , Farmacogenética/tendências , Inibidores de Simportadores de Cloreto de Sódio/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/efeitos dos fármacos , Envelhecimento/etnologia , Estudos de Coortes , Eletrocardiografia/efeitos dos fármacos , Eletrocardiografia/tendências , Feminino , Genômica/métodos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodos , Polimorfismo de Nucleotídeo Único/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único/genética
11.
Physiol Genomics ; 49(12): 747-762, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29093195

RESUMO

High-fat diet (HFD) during lactation alters milk composition and is associated with development of metabolic diseases in the offspring. We hypothesized that HFD affects milk microRNA (miRNA) and mRNA content, which potentially impact offspring development. Our objective was to determine the effect of maternal HFD on secreted milk transcriptome. To meet this objective, 4 wk old female ICR mice were divided into two treatments: control diet containing 10% kcal fat and HFD containing 60% kcal fat. After 4 wk on CD or HFD, mice were bred while continuously fed the same diets. On postnatal day 2 (P2), litters were normalized to 10 pups, and half the pups in each litter were cross-fostered between treatments. Milk was collected from dams on P10 and P12. Total RNA was isolated from milk fat fraction of P10 samples and used for mRNA-Seq and small RNA-Seq. P12 milk was used to determine macronutrient composition. After 4 wk of prepregnancy feeding HFD mice weighed significantly more than did the control mice. Lactose and fat concentration were significantly ( P < 0.05) higher in milk of HFD dams. Pup weight was significantly greater ( P < 0.05) in groups suckled by HFD vs. control dams. There were 25 miRNA and over 1,500 mRNA differentially expressed (DE) in milk of HFD vs. control dams. DE mRNA and target genes of DE miRNA enriched categories that were primarily related to multicellular organismal development. Maternal HFD impacts mRNA and miRNA content of milk, if bioactive nucleic acids are absorbed by neonate differences may affect development.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Leite/metabolismo , Animais , Gorduras/análise , Feminino , Lactação/genética , Lactação/fisiologia , Lactose/análise , Camundongos , RNA Mensageiro/genética , Transcriptoma/genética , Transcriptoma/fisiologia
12.
Osteoporos Int ; 28(9): 2583-2590, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28560474

RESUMO

In a random sample of postmenopausal Chinese women, the prevalence of radiographic vertebral fractures increased from 13% between ages 50 and 59 to over 50% after age 80 years. A model with seven clinical risk factors predicted the probability of vertebral fractures as well with as without BMD and better than a model with only three risk factors. More than half an hour of outdoor activity per day might correlate with lower risk of vertebral fracture in this population. INTRODUCTION: We aimed to describe the prevalence and develop a model for prediction of radiographic vertebral fractures in a large random sample of postmenopausal Chinese women. METHODS: We enrolled 1760 women from an age-stratified random sample of postmenopausal women in Beijing, China. The presence of vertebral fracture was assessed by semi-quantitative grading of lateral thoracolumbar radiographs, risk factors by interview, bone mineral density (BMD) of the proximal femur and lumbar spine by dual x-ray absorptiometry (DXA), and markers of bone turnover from a fasting blood sample. Associations of these factors were analyzed in logistic models and discrimination by areas of receiver operating characteristics curves (AUC). RESULTS: The prevalence of vertebral fracture, ranged from 13.4% ages 50 to 59 years old to 58.1% at age 80 years or older. Older age, a history of non-vertebral fracture, lower femoral neck BMD T-score, body mass index (BMI), height loss, housework, and less than half an hour of outdoor activity were significantly associated with increased probability of having a vertebral fracture. A model with those seven factors had a similar AUC with or without BMD and performed better than a simple model with three factors. CONCLUSION: This study is from a true random sample of postmenopausal women in urban China with high response rate. The prevalence of vertebral fractures in postmenopausal women in Beijing increases from 13% under age 60 to over 50% by age 80 years. A model with seven clinical risk factors with or without BMD is better than simple models and may guide the use of spine x-rays to identify women with vertebral fractures. More than half an hour of outdoor activity might correlate with lower risk of vertebral fracture in this population.


Assuntos
Osteoporose Pós-Menopausa/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea/fisiologia , China/epidemiologia , Exercício Físico/fisiologia , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Prevalência , Curva ROC , Fatores de Risco , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/fisiopatologia
13.
Osteoporos Int ; 28(8): 2293-2297, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28444431

RESUMO

The presence of an osteoporotic vertebral fracture improves fracture risk assessment and may change management, so it is vital for healthcare professionals to assess patients for the presence or absence of these fractures. This may be particularly important in the presence of back pain. However, the correlation between low back symptoms and spinal imaging results is poor and the pathophysiology of most low back pain is not known, leading to a common conclusion that spinal radiographs are not appropriate for the assessment of back pain. For individual patients with back pain, spinal radiographs should be considered if they have certain features in the history and examination. As well as the traditional risk factors for osteoporosis, self-reported descriptives of back pain and novel physical examination findings have been shown to make the presence of vertebral fractures more likely. Systematic approaches have the potential to improve bone health across the population but need to be targeted to be cost-effective. Spinal radiographs should be considered for individual older patients with back pain if they have certain additional features in the history and examination.


Assuntos
Fraturas por Osteoporose/diagnóstico por imagem , Fraturas da Coluna Vertebral/diagnóstico por imagem , Humanos , Dor Lombar/diagnóstico por imagem , Dor Lombar/etiologia , Fraturas por Osteoporose/complicações , Exame Físico/métodos , Radiografia , Medição de Risco/métodos , Fatores de Risco , Fraturas da Coluna Vertebral/complicações
14.
Diabet Med ; 34(1): 127-134, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27100052

RESUMO

AIM: Type 1 diabetes is the product of a complex interplay between genetic susceptibility and exposure to environmental factors. Existing bacterial profiling studies focus on people who are most at risk at the time of diagnosis; there are limited data on the gut microbiota of people with long-standing Type 1 diabetes. This study compared the gut microbiota of patients with Type 1 diabetes and good glycaemic control and high levels of physical-fitness with that of matched controls without diabetes. METHODS: Ten males with Type 1 diabetes and ten matched controls without diabetes were recruited; groups were matched for gender, age, BMI, peak oxygen uptake (VO2max ), and exercise habits. Stool samples were analysed using next-generation sequencing of the 16S rRNA gene to obtain bacterial profiles from each individual. Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was implemented to predict the functional content of the bacterial operational taxonomic units. RESULTS: Faecalibacterium sp., Roseburia sp. and Bacteroides sp. were typically the most abundant members of the community in both patients with Type 1 diabetes and controls, and were present in every sample in the cohort. Each bacterial profile was relatively individual and no significant difference was reported between the bacterial profiles or the Shannon diversity indices of Type 1 diabetes compared with controls. The functional profiles were more conserved and the Type 1 diabetes group were comparable with the control group. CONCLUSIONS: We show that both gut microbiota and resulting functional bacterial profiles from patients with long-standing Type 1 diabetes in good glycaemic control and high physical fitness levels are comparable with those of matched people without diabetes.


Assuntos
Bacteroides/isolamento & purificação , Clostridiales/isolamento & purificação , Diabetes Mellitus Tipo 1/microbiologia , Disbiose/prevenção & controle , Faecalibacterium/isolamento & purificação , Microbioma Gastrointestinal , Adulto , Bacteroides/crescimento & desenvolvimento , Estudos de Casos e Controles , Clostridiales/crescimento & desenvolvimento , Estudos de Coortes , Terapia Combinada , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Disbiose/complicações , Disbiose/epidemiologia , Disbiose/microbiologia , Inglaterra/epidemiologia , Exercício Físico , Faecalibacterium/crescimento & desenvolvimento , Fezes/microbiologia , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/prevenção & controle , Hipoglicemia/prevenção & controle , Masculino , Consumo de Oxigênio , Filogenia , Aptidão Física , Risco
15.
Sci Rep ; 6: 26985, 2016 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-27245316

RESUMO

Gastro-Oesophageal Reflux (GOR) is a key problem in Cystic Fibrosis (CF), but the relationship between lung and gastric microbiomes is not well understood. We hypothesised that CF gastric and lung microbiomes are related. Gastric and sputum cultures were obtained from fifteen CF patients receiving percutaneous endoscopic gastrostomy feeding. Non-CF gastric juice data was obtained through endoscopy from 14 patients without lung disease. Bacterial and fungal isolates were identified by culture. Molecular bacterial profiling used next generation sequencing (NGS) of the 16S rRNA gene. Cultures grew bacteria and/or fungi in all CF gastric juice and sputa and in 9/14 non-CF gastric juices. Pseudomonas aeruginosa(Pa) was present in CF sputum in 11 patients, 4 had identical Pa strains in the stomach. NGS data from non-CF gastric juice samples were significantly more diverse compared to CF samples. NGS showed CF gastric juice had markedly lower abundance of normal gut bacteria; Bacteroides and Faecalibacterium, but increased Pseudomonas compared with non-CF. Multivariate partial least squares discriminant analysis demonstrated similar bacterial profiles of CF sputum and gastric juice samples, which were distinct from non-CF gastric juice. We provide novel evidence suggesting the existence of an aerodigestive microbiome in CF, which may have clinical relevance.


Assuntos
Fibrose Cística/microbiologia , Suco Gástrico/microbiologia , Refluxo Gastroesofágico/microbiologia , Microbiota/genética , Escarro/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Tipagem Bacteriana , Bacteroides/classificação , Bacteroides/genética , Bacteroides/isolamento & purificação , Fibrose Cística/complicações , Fibrose Cística/patologia , Análise Discriminante , Faecalibacterium/classificação , Faecalibacterium/genética , Faecalibacterium/isolamento & purificação , Feminino , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/patologia , Gastrostomia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pulmão/microbiologia , Masculino , Pessoa de Meia-Idade , Nutrição Parenteral , Pseudomonas aeruginosa/classificação , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/isolamento & purificação , RNA Ribossômico 16S/genética , Estômago/microbiologia
16.
J Clin Endocrinol Metab ; 101(8): 3163-70, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27270237

RESUMO

CONTEXT: Denosumab and zoledronic acid (ZOL) are parenteral treatments for patients with osteoporosis. OBJECTIVE: The objective of the study was to compare the effect of transitioning from oral bisphosphonates to denosumab or ZOL on bone mineral density (BMD) and bone turnover. DESIGN AND SETTING: This was an international, multicenter, randomized, double-blind trial. PARTICIPANTS: A total of 643 postmenopausal women with osteoporosis previously treated with oral bisphosphonates participated in the study. INTERVENTIONS: Subjects were randomized 1:1 to sc denosumab 60 mg every 6 months plus iv placebo once or ZOL 5 mg iv once plus sc placebo every 6 months for 12 months. MAIN OUTCOME MEASURES: Changes in BMD and bone turnover markers were measured. RESULTS: BMD change from baseline at month 12 was significantly greater with denosumab compared with ZOL at the lumbar spine (primary end point; 3.2% vs 1.1%; P < .0001), total hip (1.9% vs 0.6%; P < .0001), femoral neck (1.2% vs -0.1%; P < .0001), and one-third radius (0.6% vs 0.0%; P < .05). The median decrease from baseline was greater with denosumab than ZOL for serum C-telopeptide of type 1 collagen at all time points after day 10 and for serum procollagen type 1 N-terminal propeptide at month 1 and at all time points after month 3 (all P < .05). Median percentage changes from baseline in serum intact PTH were significantly greater at months 3 and 9 with denosumab compared with ZOL (all P < .05). Adverse events were similar between groups. Three events consistent with the definition of atypical femoral fracture were observed (two denosumab and one ZOL). CONCLUSIONS: In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL.


Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Denosumab/uso terapêutico , Difosfonatos/administração & dosagem , Imidazóis/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Administração Oral , Idoso , Densidade Óssea/efeitos dos fármacos , Difosfonatos/uso terapêutico , Método Duplo-Cego , Substituição de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Ácido Zoledrônico
17.
J Intern Med ; 277(6): 650-61, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25832448

RESUMO

The global trend towards increased longevity has resulted in ageing populations and a rise in diseases or conditions that primarily affect older persons. One such condition is osteoporosis (fragile or porous bones), which causes an increased fracture risk. Vertebral and hip fractures lead to increased morbidity and mortality and result in enormous healthcare costs. Here, we review the evolution of the diagnosis of osteoporosis. In an attempt to separate patients with normal bones from those with osteoporosis and to define the osteoporosis diagnosis, multiple factors and characteristics have been considered. These include pathology and histology of the disease, the endocrine regulation of bone metabolism, bone mineral density (BMD), fracture type or trauma severity, risk models for fracture prediction, and thresholds for pharmacological intervention. The femoral neck BMD -2.5 SDs cut-off for the diagnosis of osteoporosis is arbitrarily chosen, and there is no evidence to support the notion that fracture location (except vertebral fractures) or severity is useful to discriminate osteoporotic from normal bones. Fracture risk models (including factors unrelated to bone) dissociate bone strength from the diagnosis, and treatment thresholds are often based on health-economic considerations rather than bone properties. Vertebral fractures are a primary feature of osteoporosis, characterized by decreased bone mass, strength and quality, and a high risk of another such fracture that can be considerably reduced by treatment. We believe that the 2001 definition of osteoporosis by the National Institutes of Health Consensus Development Panel on Osteoporosis is still valid and useful: 'Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture'.


Assuntos
Absorciometria de Fóton , Envelhecimento , Densidade Óssea , Osteoporose/diagnóstico , Absorciometria de Fóton/métodos , Alendronato/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Fraturas Ósseas/etiologia , Fraturas Ósseas/prevenção & controle , Fraturas do Quadril/etiologia , Humanos , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Fatores de Risco , Resultado do Tratamento
18.
J Appl Microbiol ; 119(1): 208-14, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25866080

RESUMO

AIMS: To identify changes in the bacterial community, at the phylum level brought about by varied crop management. METHODS AND RESULTS: Next-generation sequencing methods were used to compare the taxonomic structure of the bacterial community within 24 agricultural soils managed with either organic or conventional methods, over a 3-year period. Relative abundance of the proportionately larger phyla (e.g. Acidobacteria and Actinobacteria) was primarily affected by sample year rather than crop management. Changes of abundance in these phyla were correlated with changes in pH, organic nitrogen and soil basal respiration. Crop management affected some of the less dominant phyla (Chloroflexi, Nitrospirae, Gemmatimonadetes) which also correlated with pH and organic N. CONCLUSION: Soil diversity can vary with changing environmental variables and soil chemistry. If these factors remain constant, soil diversity can also remain constant even under changing land use. SIGNIFICANCE AND IMPACT OF THE STUDY: The impact of crop management on environmental variables must be considered when interpreting bacterial diversity studies in agricultural soils. Impact of land use change should always be monitored across different sampling time points. Further studies at the functional group level are necessary to assess whether management-induced changes in bacterial community structure are of biological and agronomic relevance.


Assuntos
Agricultura/métodos , Bactérias/isolamento & purificação , Produtos Agrícolas/crescimento & desenvolvimento , Microbiologia do Solo , Bactérias/classificação , Bactérias/genética , Biodiversidade , Dados de Sequência Molecular , Nitrogênio/análise , Nitrogênio/metabolismo , RNA Ribossômico 16S , Solo/química
19.
J Clin Endocrinol Metab ; 100(4): 1343-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25642590

RESUMO

CONTEXT: Higher dietary net acid loads have been associated with increased bone resorption, reduced bone mineral density (BMD), and increased fracture risk. OBJECTIVE: The objective was to compare bicarbonate (HCO3) measured in arterialized venous blood samples to skeletal outcomes. DESIGN: Arterialized venous samples collected from participants in the Health, Aging and Body Composition (Health ABC) Study were compared to BMD and rate of bone loss. SETTING: The setting was a community-based observational cohort. PARTICIPANTS: A total of 2287 men and women age 74 ± 3 years participated. INTERVENTION: Arterialized venous blood was obtained at the year 3 study visit and analyzed for pH and pCO2. HCO3 was determined using the Henderson-Hasselbalch equation. MAIN OUTCOME MEASURE: BMD was measured at the hip by dual-energy x-ray absorptiometry at the year 1 (baseline) and year 3 study visits. RESULTS: Plasma HCO3 was positively associated with BMD at both year 1 (P = .001) and year 3 (P = .001) in models adjusted for age, race, sex, clinic site, smoking, weight, and estimated glomerular filtration rate. Plasma HCO3 was inversely associated with rate of bone loss at the total hip over the 2.1 ± 0.3 (mean ± SD) years between the two bone density measurements (P < .001). Across quartiles of plasma HCO3, the rate of change in BMD over the 2.1 years ranged from a loss of 0.72%/y in the lowest quartile to a gain of 0.15%/y in the highest quartile of HCO3. CONCLUSIONS: Arterialized plasma HCO3 was associated positively with cross-sectional BMD and inversely with the rate of bone loss, implying that systemic acid-base status is an important determinant of skeletal health during aging. Ongoing bone loss was linearly related to arterialized HCO3, even after adjustment for age and renal function. Further research in this area may have major public health implications because reducing dietary net acid load is possible through dietary intervention or through supplementation with alkaline potassium compounds.


Assuntos
Envelhecimento/fisiologia , Bicarbonatos/sangue , Densidade Óssea , Reabsorção Óssea , Osteoporose/sangue , Idoso , Envelhecimento/sangue , Gasometria/métodos , Composição Corporal/fisiologia , Reabsorção Óssea/sangue , Reabsorção Óssea/fisiopatologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Osteoporose/fisiopatologia
20.
Eur J Clin Microbiol Infect Dis ; 34(3): 519-25, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25308827

RESUMO

The purpose of this study was to evaluate a new chromogenic medium, chromID OXA-48, for the isolation of carbapenemase-producing Enterobacteriaceae (CPE) directly from rectal swabs. chromID CARBA and chromID OXA-48 are two chromogenic media that have been commercialized for the isolation of CPE directly from clinical samples. Both media were evaluated alongside a broth enrichment method recommended by the CDC for isolation of CPE, with rectal swabs from 302 unique hospitalized patients at the Hacettepe University Hospital, Ankara, Turkey. A total of 33 patients (11 %) were found to be colonized with CPE using a combination of all methods, and all CPE produced OXA-48 carbapenemase. Klebsiella pneumoniae was by far the most dominant species of CPE and was isolated from 31 patients. Culture on chromID OXA-48 offered the highest sensitivity (75.8 %) for detection of CPE compared with the other two methods (sensitivity for both other methods was 57.6 %) and also offered the highest specificity (99.3 %). However, a combination of methods (either chromID OXA-48 plus CDC method or chromID OXA-48 plus chromID CARBA) was necessary to achieve an acceptable sensitivity (90.9 %). For isolation of CPE, in a setting where OXA-48 carbapenemase is the dominant type of carbapenemase, chromID OXA-48 is a highly useful medium but using a combination of methods is optimal for adequate detection. The combined use of two chromogenic media offered acceptable sensitivity (90.9 %) and the highest specificity (98.5 %) and also allowed for isolation of CPE within 18-20 h.


Assuntos
Proteínas de Bactérias/análise , Técnicas Bacteriológicas/métodos , Meios de Cultura/química , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/enzimologia , Enterobacteriaceae/isolamento & purificação , beta-Lactamases/análise , Compostos Cromogênicos/metabolismo , Cor , Hospitais Universitários , Humanos , Reto/microbiologia , Sensibilidade e Especificidade , Turquia
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