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2.
Bone Joint J ; 102-B(1): 72-81, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31888363

RESUMO

AIMS: The early mortality in patients with hip fractures from bony metastases is unknown. The objectives of this study were to quantify 30- and 90-day mortality in patients with proximal femoral metastases, and to create a mortality prediction tool based on biomarkers associated with early death. METHODS: This was a retrospective cohort study of consecutive patients referred to the orthopaedic department at a UK trauma centre with a proximal femoral metastasis (PFM) over a seven-year period (2010 to 2016). The study group were compared to a matched control group of non-metastatic hip fractures. Minimum follow-up was one year. RESULTS: There was a 90-day mortality of 46% in patients with metastatic hip fractures versus 12% in controls (89/195 and 24/192, respectively; p < 0.001). Mean time to surgery was longer in symptomatic metastases versus complete fractures (9.5 days (SD 19.8) and 3.4 days (SD 11.4), respectively; p < 0.05). Albumin, urea, and corrected calcium were all independent predictors of early mortality and were used to generate a simple tool for predicting 90-day mortality, titled the Metastatic Early Prognostic (MEP) score. An MEP score of 0 was associated with the lowest risk of death at 30 days (14%, 3/21), 90 days (19%, 4/21), and one year (62%, 13/21). MEP scores of 3/4 were associated with the highest risk of death at 30 days (56%, 5/9), 90 days (100%, 9/9), and one year (100%, 9/9). Neither age nor primary cancer diagnosis was an independent predictor of mortality at 30 and 90 days. CONCLUSION: This score could be used to predict early mortality and guide perioperative counselling. The delay to surgery identifies a potential window to intervene and correct these abnormalities with the aim of improving survival. Cite this article: Bone Joint J. 2020;102-B(1):72-81.


Assuntos
Neoplasias Femorais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Feminino , Neoplasias Femorais/secundário , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Escócia/epidemiologia , Índice de Gravidade de Doença , Análise de Sobrevida , Tempo para o Tratamento
4.
Artigo em Inglês | MEDLINE | ID: mdl-31725531

RESUMO

OBJECTIVES: Extracorporeal membrane oxygenation is a treatment for Persistent Pulmonary Hypertension of the Newborn with high mortality. HYPOTHESIS: the extracorporeal membrane oxygenation circuit results in inflammatory responses that mitigate against successful weaning. DESIGN: Single-center prospective observational feasibility study. SETTING: PICU. PATIENTS: Twenty-four neonates requiring extracorporeal membrane oxygenation support for Persistent Pulmonary Hypertension of the Newborn. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The reference outcome was death or more than 7 days of extracorporeal membrane oxygenation support. Other outcomes included serial measures of plasma-free hemoglobin and markers of its metabolism, leucocyte, platelet and endothelial activation, and biomarkers of inflammation. Of 24 participants recruited between February 2016 and June 2017, 10 died or required prolonged extracorporeal membrane oxygenation support. These patients were sicker at baseline with higher levels of plasma-free hemoglobin within 12 hours of cannulation (geometric mean ratio, 1.92; 95% CIs, 1.00-3.67; p = 0.050) but not thereafter, versus those requiring less than 7 days extracorporeal membrane oxygenation. Serum haptoglobin concentrations were significantly elevated in both groups. Patients who died or required prolonged extracorporeal membrane oxygenation support demonstrated elevated levels of platelet-leucocyte aggregation, but decreased concentrations of mediators of the inflammatory response: interleukin-8, C-reactive protein, and tumor necrosis factor α. CONCLUSIONS: Clinical status at baseline and not levels of plasma-free hemoglobin or the systemic inflammatory response may determine the requirement for prolonged extracorporeal membrane oxygenation support in neonates.

5.
J Infect ; 79(4): 373-382, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31323249

RESUMO

OBJECTIVES: To improve our understanding of the global epidemiology of common respiratory viruses by analysing their contemporaneous incidence at multiple sites. METHODS: 2010-2015 incidence data for influenza A (IAV), influenza B (IBV), respiratory syncytial (RSV) and parainfluenza (PIV) virus infections were collected from 18 sites (14 countries), consisting of local (n = 6), regional (n = 9) and national (n = 3) laboratories using molecular diagnostic methods. Each site submitted monthly virus incidence data, together with details of their patient populations tested and diagnostic assays used. RESULTS: For the Northern Hemisphere temperate countries, the IAV, IBV and RSV incidence peaks were 2-6 months out of phase with those in the Southern Hemisphere, with IAV having a sharp out-of-phase difference at 6 months, whereas IBV and RSV showed more variable out-of-phase differences of 2-6 months. The tropical sites Singapore and Kuala Lumpur showed fluctuating incidence of these viruses throughout the year, whereas subtropical sites such as Hong Kong, Brisbane and Sydney showed distinctive biannual peaks for IAV but not for RSV and PIV. CONCLUSIONS: There was a notable pattern of synchrony of IAV, IBV and RSV incidence peaks globally, and within countries with multiple sampling sites (Canada, UK, Australia), despite significant distances between these sites.

6.
BMC Cardiovasc Disord ; 19(1): 24, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30665364

RESUMO

Following publication of the original article [1], the author reported his name has erroneously spelled as Abishek Shetye. The correct name is Abhishek Shetye.

7.
Circ Genom Precis Med ; 12(1): e002196, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30645167

RESUMO

BACKGROUND: Although short-term trials have suggested that PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are safe and reduce risk of cardiovascular diseases, their long-term safety is unclear. Genetic variants associated with lower activity of a gene can act as proxies to identify potential long-term side effects of drugs as recently exemplified by association of LDL (low-density lipoprotein)-lowering variants in the HMGCR (target for statins) and PCSK9 genes with increased risk of type 2 diabetes mellitus (T2DM). However, analyses of the full spectrum of potential side effects of PCSK9 inhibition using a genetic approach have not been undertaken. METHODS: We examined the association of an LDL-lowering variant in the PCSK9 gene (T allele of rs1159147), as well as 2 LDL-lowering HGCMR variants (G allele of rs17238484 and T allele of rs12916) with 80 diseases and traits in up to 479 522 individuals in UK Biobank. RESULTS: The PCSK9 T allele was significantly (Bonferroni P<6.25×10-4) associated with risk of T2DM, increased body mass index, waist circumference, waist-hip ratio, diastolic blood pressure, type 1 diabetes mellitus, and insulin use. The HMGCR variants were also associated with risk of T2DM, although their previously reported associations with anthropometric traits were found to be confounded. Mediation analysis suggested that the association of the PCSK9 T allele with risk of T2DM but not diastolic blood pressure was largely independent of its association with body mass index and central obesity. Nominally significant associations of the PCSK9 T allele were also seen with peptic ulcer disease, depression, asthma, chronic kidney disease, and venous thromboembolism. CONCLUSIONS: Our findings support previous genetic analyses suggesting that long-term use of PCSK9 inhibitors, like statins, may be associated with increased risk of T2DM. Some other potential side effects need to be looked for in future studies of PCSK9 inhibitors, although we did not find signals that raise substantial concerns about their long-term safety.

8.
Int J Cardiol ; 278: 157-161, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30528627

RESUMO

BACKGROUND: In patients with heart failure, downregulation of adenosine receptor gene expression and impaired adenosine-related signal transduction may result in a diminished response to adenosine. This may have implications for cardiac stress testing. We evaluated the haemodynamic response to intravenous adenosine in patients with left ventricular systolic dysfunction (LVSD) undergoing stress cardiovascular magnetic resonance imaging (CMR). METHODS AND RESULTS: We retrospectively examined 497 consecutive patients referred for clinical stress CMR. Blood pressure and heart rate responses with intravenous adenosine were compared in patients with normal, mild-moderately impaired and severely impaired LV systolic function (ejection fraction [EF] > 55%, 36-55% and < 35%, respectively). Following 2 min of adenosine infusion, there was a significant difference between the groups in the heart rate change from baseline, with a diminished heart rate response in patients with LVSD (p < 0.001). An increase in the dose of adenosine (up to 210 µg/kg/min) was required to achieve a sufficient haemodynamic response in more patients with severe LVSD (41%) than those with mild-moderately impaired and normal LV systolic function (24% and 19%, respectively, p < 0.001). Even with increased doses of adenosine in subjects with severe LVSD, peak haemodynamic response remained blunted. With multivariate analysis age (p < 0.001) and LVEF (p = 0.031) were independent predictors of heart rate response to adenosine. CONCLUSION: Patients with reduced LVEF referred for stress CMR may have a blunted heart rate response to adenosine. Further study is warranted to determine whether this may be associated with reduced diagnostic accuracy and also the potential utility of further dose increases or alternative stressors.


Assuntos
Adenosina/administração & dosagem , Teste de Esforço/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Administração Intravenosa , Idoso , Teste de Esforço/métodos , Feminino , Frequência Cardíaca/fisiologia , Hemodinâmica/fisiologia , Humanos , Imagem Cinética por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Disfunção Ventricular Esquerda/fisiopatologia
9.
Transl Res ; 205: 1-16, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30528323

RESUMO

The clinical efficacy of organ protection interventions are limited by the redundancy of cellular activation mechanisms. Interventions that target epigenetic mechanisms overcome this by eliciting genome wide changes in transcription and signaling. We aimed to review preclinical studies evaluating the organ protection effects of histone deacetylase inhibitors (HDACi) with a view to informing the design of early phase clinical trials. A systematic literature search was performed. Methodological quality was assessed against prespecified criteria. The primary outcome was mortality, with secondary outcomes assessing mechanisms. Prespecified analyses evaluated the effects of likely moderators on heterogeneity. The analysis included 101 experimental studies in rodents (n = 92) and swine (n = 9), exposed to diverse injuries, including: ischemia (n = 72), infection (n = 7), and trauma (n = 22). There were a total of 448 comparisons due to the evaluation of multiple independent interventions within single studies. Sodium valproate (VPA) was the most commonly evaluated HDACi (50 studies, 203 comparisons). All of the studies were judged to have significant methodological limitations. HDACi reduced mortality in experimental models of organ injury (risk ratio = 0.52, 95% confidence interval 0.40-0.68, p < 0.001) without heterogeneity. HDACi administration resulted in myocardial, brain and kidney protection across diverse species and injuries that was attributable to increases in prosurvival cell signaling, and reductions in inflammation and programmed cell death. Heterogeneity in the analyses of secondary outcomes was explained by differences in species, type of injury, HDACi class (Class I better), drug (trichostatin better), and time of administration (at least 6 hours prior to injury better). These findings highlight a potential novel application for HDACi in clinical settings characterized by acute organ injury.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Preservação de Órgãos/métodos , Animais , Inibidores de Histona Desacetilases/administração & dosagem , Humanos , Pesquisa Médica Translacional
10.
Pediatr Infect Dis J ; 38(2): e36-e38, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30001232

RESUMO

Comparison of children hospitalized with enterovirus or human parechovirus (HPeV) detected in their cerebrospinal fluid revealed that HPeV infections presented with more persistent fever, irritability and feeding problems, more frequent leukopenia and lymphopenia and higher admission rates to high dependency or intensive care units. Few HPeV cases were followed up, further studies on long-term outcomes are needed.

11.
Clin Kidney J ; 11(6): 864-873, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30524722

RESUMO

Background: Aortic stiffness is one of the earliest signs of cardiovascular disease (CVD) in patients with chronic kidney disease and an independent predictor of mortality. It is thought to drive left ventricular (LV) remodelling, an established biomarker for mortality. The relationship between direct and indirect measures of aortic stiffness and LV remodelling is not defined in dialysis patients, nor are the reproducibility of methods used to assess aortic stiffness using cardiac magnetic resonance (CMR) imaging. Methods: Using 3T CMR, we report the results of (i) the interstudy, interobserver and intra-observer reproducibility of ascending aortic distensibility (AAD), descending aortic distensibility (DAD) and aortic pulse wave velocity (aPWV) in 10 haemodialysis (HD) patients and (ii) the relationship between AAD, DAD and aPWV and LV mass index (LVMi) and LV remodelling in 70 HD patients. Results: Inter- and intra-observer variability of AAD, DAD and aPWV were excellent [intraclass correlation (ICC) > 0.9 for all]. Interstudy reproducibility of AAD was excellent {ICC 0.94 [95% confidence interval (CI) 0.78-0.99]}, but poor for DAD and aPWV [ICC 0.51 (-0.13-0.85) and 0.51 (-0.31-0.89)]. AAD, DAD and aPWV associated with LVMi on univariate analysis (ß = -0.244, P = 0.04; ß =-0.315, P < 0.001 and ß = 0.242, P = 0.04, respectively). Only systolic blood pressure, serum phosphate and a history of CVD remained independent determinants of LVMi on multivariable linear regression. Conclusions: AAD is the most reproducible CMR-derived measure of aortic stiffness in HD patients. CMR-derived measures of aortic stiffness were not independent determinants of LVMi in HD patients. Whether one should target blood pressure over aortic stiffness to mitigate cardiovascular risk still needs determination.

12.
J Am Coll Cardiol ; 72(16): 1883-1893, 2018 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-30309464

RESUMO

BACKGROUND: Coronary artery disease (CAD) has substantial heritability and a polygenic architecture. However, the potential of genomic risk scores to help predict CAD outcomes has not been evaluated comprehensively, because available studies have involved limited genomic scope and limited sample sizes. OBJECTIVES: This study sought to construct a genomic risk score for CAD and to estimate its potential as a screening tool for primary prevention. METHODS: Using a meta-analytic approach to combine large-scale, genome-wide, and targeted genetic association data, we developed a new genomic risk score for CAD (metaGRS) consisting of 1.7 million genetic variants. We externally tested metaGRS, both by itself and in combination with available data on conventional risk factors, in 22,242 CAD cases and 460,387 noncases from the UK Biobank. RESULTS: The hazard ratio (HR) for CAD was 1.71 (95% confidence interval [CI]: 1.68 to 1.73) per SD increase in metaGRS, an association larger than any other externally tested genetic risk score previously published. The metaGRS stratified individuals into significantly different life course trajectories of CAD risk, with those in the top 20% of metaGRS distribution having an HR of 4.17 (95% CI: 3.97 to 4.38) compared with those in the bottom 20%. The corresponding HR was 2.83 (95% CI: 2.61 to 3.07) among individuals on lipid-lowering or antihypertensive medications. The metaGRS had a higher C-index (C = 0.623; 95% CI: 0.615 to 0.631) for incident CAD than any of 6 conventional factors (smoking, diabetes, hypertension, body mass index, self-reported high cholesterol, and family history). For men in the top 20% of metaGRS with >2 conventional factors, 10% cumulative risk of CAD was reached by 48 years of age. CONCLUSIONS: The genomic score developed and evaluated here substantially advances the concept of using genomic information to stratify individuals with different trajectories of CAD risk and highlights the potential for genomic screening in early life to complement conventional risk prediction.


Assuntos
Doença da Artéria Coronariana , Genômica , Prevenção Primária/métodos , Medição de Risco/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/genética , Feminino , Estudo de Associação Genômica Ampla , Genômica/métodos , Genômica/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Herança Multifatorial , Valor Preditivo dos Testes , Projetos de Pesquisa , Fatores de Risco , Reino Unido/epidemiologia
13.
BMC Med ; 16(1): 187, 2018 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-30355295

RESUMO

BACKGROUND: Adult height is associated with risk of several diseases, but the breadth of such associations and whether these associations are primary or due to confounding are unclear. We examined the association of adult height with 50 diseases spanning multiple body systems using both epidemiological and genetic approaches, the latter to identify un-confounded associations and possible underlying mechanisms. METHODS: We examined the associations for adult height (using logistic regression adjusted for potential confounders) and genetically determined height (using a two-sample Mendelian randomisation approach with height-associated genetic variants as instrumental variables) in 417,434 individuals of white ethnic background participating in the UK Biobank. We undertook pathway analysis of height-associated genes to identify biological processes that could link height and specific diseases. RESULTS: Height was associated with 32 diseases and genetically determined height associated with 12 diseases. Of these, 11 diseases showed a concordant association in both analyses, with taller height associated with reduced risks of coronary artery disease (odds ratio per standard deviation (SD) increase in height ORepi = 0.80, 95% CI 0.78-0.81; OR per SD increase in genetically determined height ORgen = 0.86, 95% CI 0.82-0.90), hypertension (ORepi = 0.83, 95% CI 0.82-0.84; ORgen = 0.88, 95% CI 0.85-0.91), gastro-oesophageal reflux disease (ORepi = 0.85, 95% CI 0.84-0.86; ORgen = 0.94, 95% CI 0.92-0.97), diaphragmatic hernia (ORepi = 0.81, 95% CI 0.79-0.82; ORgen = 0.91, 95% CI 0.88-0.94), but increased risks of atrial fibrillation (ORepi = 1.42, 95% CI 1.38-1.45; ORgen = 1.33, 95% CI 1.26-1.40), venous thromboembolism (ORepi = 1.18, 95% CI 1.16-1.21; ORgen = 1.15, 95% CI 1.11-1.19), intervertebral disc disorder (ORepi = 1.15, 95% CI 1.13-1.18; ORgen = 1.14, 95% CI 1.09-1.20), hip fracture (ORepi = 1.19, 95% CI 1.12-1.26; ORgen = 1.27, 95% CI 1.17-1.39), vasculitis (ORepi = 1.15, 95% CI 1.11-1.19; ORgen = 1.20, 95% CI 1.14-1.28), cancer overall (ORepi = 1.09, 95% CI 1.08-1.11; ORgen = 1.06, 95% CI 1.04-1.08) and breast cancer (ORepi = 1.08, 95% CI 1.06-1.10; ORgen = 1.07, 95% CI 1.03-1.11). Pathway analysis showed multiple height-associated pathways associating with individual diseases. CONCLUSIONS: Adult height is associated with risk of a range of diseases. We confirmed previously reported height associations for coronary artery disease, atrial fibrillation, venous thromboembolism, intervertebral disc disorder, hip fracture and cancer and identified potential novel associations for gastro-oesophageal reflux disease, diaphragmatic hernia and vasculitis. Multiple biological mechanisms affecting height may affect the risks of these diseases.


Assuntos
Estatura/genética , Doença/genética , Testes Genéticos/métodos , Análise da Randomização Mendeliana/métodos , Adulto , Idoso , Doença/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
14.
Heart ; 104(23): 1955-1962, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29748420

RESUMO

BACKGROUND: Remote ischaemic conditioning (rIC) is a cardioprotective tool which has shown promise in preclinical and clinical trials in the context of acute ischaemia. Repeated rIC post myocardial infarction may provide additional benefits which have not previously been tested clinically. METHODS: The trial assessed the role of daily rIC in enhancing left ventricular ejection fraction (LVEF) recovery in patients with impaired LVEF (<45%) after ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (P-PCI). Patients were recruited from four UK hospitals and randomised to receive either 4 weeks of daily rIC or sham conditioning using the autoRIC Device (CellAegis) starting on day 3 post P-PCI. The primary endpoint was the improvement in LVEF over 4 months assessed by cardiac MRI (CMR). Seventy-three patients (38 cases, 35 controls) completed the study. RESULTS: The treatment and control groups were well matched at baseline including for mean LVEF (42.8% vs 44.3% respectively, p=0.952). There was no difference in the improvement in LVEF over 4 months between the treatment and control groups (4.8%±7.8% vs 4.6%±5.9% respectively, p=0.924). No differences were seen in the secondary outcome measures including changes in infarct size and left ventricular end-diastolic and systolic volumes, major adverse cardiac and cerebral event, mean Kansas City Cardiomyopathy Questionnaire score and change in N-terminal pro-brain natriuretic peptide levels. CONCLUSIONS: Daily rIC starting on day 3 and continued for 4 weeks following successful P-PCI for STEMI did not improve LVEF as assessed by CMR after 4 months when compared with a matched control group. TRIAL REGISTRATION NUMBER: NCT0166461.


Assuntos
Precondicionamento Isquêmico Miocárdico/métodos , Intervenção Coronária Percutânea , Complicações Pós-Operatórias/prevenção & controle , Infarto do Miocárdio com Supradesnível do Segmento ST , Disfunção Ventricular Esquerda , Idoso , Feminino , Monitorização Hemodinâmica/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/análise , Fragmentos de Peptídeos/análise , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Volume Sistólico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/prevenção & controle
15.
Diabetes ; 67(7): 1395-1400, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29661781

RESUMO

Individuals with type 2 diabetes have a three- to fivefold increased risk of developing heart failure. Diabetic cardiomyopathy is typified by left ventricular (LV) concentric remodeling, which is a recognized predictor of adverse cardiovascular events. Although the mechanisms underlying LV remodeling in type 2 diabetes are unclear, progressive aortic stiffening may be a key determinant. The aim of this study was to assess the relationship between aortic stiffness and LV geometry in younger adults with type 2 diabetes, using multiparametric cardiovascular MRI. We prospectively recruited 80 adults (aged 18-65 years) with type 2 diabetes and no cardiovascular disease and 20 age- and sex-matched healthy control subjects. All subjects underwent comprehensive bio-anthropometric assessment and cardiac MRI, including measurement of aortic stiffness by aortic distensibility (AD). Type 2 diabetes was associated with increased LV mass, concentric LV remodeling, and lower AD compared with control subjects. On multivariable linear regression, AD was independently associated with concentric LV remodeling in type 2 diabetes. Aortic stiffness may therefore be a potential therapeutic target to prevent the development of heart failure in type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Rigidez Vascular/fisiologia , Remodelação Ventricular/fisiologia , Adolescente , Adulto , Idoso , Doenças da Aorta/diagnóstico , Doenças da Aorta/epidemiologia , Doenças da Aorta/etiologia , Doenças da Aorta/fisiopatologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/fisiopatologia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/diagnóstico , Hipertrofia Ventricular Esquerda/epidemiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
17.
Hypertension ; 70(5): 1042-1048, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28847892

RESUMO

We hypothesized that screening for nonadherence to antihypertensive treatment using liquid chromatography-tandem mass spectrometry-based biochemical analysis of urine/serum has therapeutic applications in nonadherent hypertensive patients. A retrospective analysis of hypertensive patients attending specialist tertiary care centers was conducted in 2 European countries (United Kingdom and Czech Republic). Nonadherence to antihypertensive treatment was diagnosed using biochemical analysis of urine (United Kingdom) or serum (Czech Republic). These results were subsequently discussed with each patient, and data on follow-up clinic blood pressure (BP) measurements were collected from clinical files. Of 238 UK patients who underwent biochemical urine analysis, 73 were nonadherent to antihypertensive treatment. Their initial urinary adherence ratio (the ratio of detected to prescribed antihypertensive medications) increased from 0.33 (0-0.67) to 1 (0.67-1) between the first and the last clinic appointments. The observed increase in the urinary adherence ratio in initially nonadherent UK patients was associated with the improved BP control; by the last clinic appointment, systolic and diastolic BPs were ≈19.5 and 7.5 mm Hg lower than at baseline (P=0.001 and 0.009, respectively). These findings were further corroborated in 93 nonadherent hypertensive patients from Czech Republic-their average systolic and diastolic BPs dropped by ≈32.6 and 17.4 mm Hg, respectively (P<0.001), on appointments after the biochemical analysis. Our data show that nonadherent hypertensive patients respond to liquid chromatography-tandem mass spectrometry-based biochemical analysis with improved adherence and significant BP drop. Such repeated biochemical analyses should be considered as a therapeutic approach in nonadherent hypertensive patients.


Assuntos
Anti-Hipertensivos , Biomarcadores , Pressão Sanguínea/efeitos dos fármacos , Hipertensão , Adesão à Medicação/psicologia , Conduta do Tratamento Medicamentoso/normas , Adulto , Idoso , Anti-Hipertensivos/análise , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangue , Biomarcadores/urina , Determinação da Pressão Arterial/métodos , Determinação da Pressão Arterial/psicologia , Cromatografia Líquida/métodos , República Tcheca/epidemiologia , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Melhoria de Qualidade , Reino Unido/epidemiologia
18.
Nat Genet ; 49(9): 1385-1391, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28714975

RESUMO

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10-8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; ncases = 10,801) as well as a stricter definition without angina (HARD; ncases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.


Assuntos
Doença da Artéria Coronariana/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Estudos de Associação Genética/métodos , Estudos de Associação Genética/normas , Estudos de Associação Genética/estatística & dados numéricos , Estudo de Associação Genômica Ampla/normas , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Genótipo , Sistemas de Informação em Saúde/normas , Sistemas de Informação em Saúde/estatística & dados numéricos , Humanos , Metanálise como Assunto , Fenótipo , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , Fatores de Risco , Reino Unido
19.
Hypertension ; 69(6): 1113-1120, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28461599

RESUMO

Nonadherence to antihypertensive treatment is a critical contributor to suboptimal blood pressure control. There are limited and heterogeneous data on the risk factors for nonadherence because few studies used objective-direct diagnostic methods. We used high-performance liquid chromatography-tandem mass spectrometry of urine and serum to detect nonadherence and explored its association with the main demographic- and therapy-related factors in 1348 patients with hypertension from 2 European countries. The rates of nonadherence to antihypertensive treatment were 41.6% and 31.5% in the UK and Czech populations, respectively. Nonadherence was inversely related to age and male sex. Each increase in the number of antihypertensive medications led to 85% and 77% increase in nonadherence (P<0.001) in the UK and Czech populations, respectively. The odds of nonadherence to diuretics were the highest among 5 classes of antihypertensive medications (P≤0.005 in both populations). The predictive model for nonadherence, including age, sex, diuretics, and the number of prescribed antihypertensives, showed area under the curves of 0.758 and 0.710 in the UK and Czech populations, respectively. The area under the curves for the UK model tested on the Czech data and for the Czech model tested on UK data were calculated at 0.708 and 0.756, respectively. We demonstrate that the number and class of prescribed antihypertensives are modifiable risk factors for biochemically confirmed nonadherence to blood pressure-lowering therapy. Further development of discriminatory models incorporating these parameters might prove clinically useful in assessment of nonadherence in countries where biochemical analysis is unavailable.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diuréticos/uso terapêutico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Fatores Etários , Idoso , Determinação da Pressão Arterial/métodos , Estudos de Coortes , República Tcheca , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Reino Unido
20.
BMC Cardiovasc Disord ; 17(1): 98, 2017 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-28390413

RESUMO

BACKGROUND: Late gadolinium enhanced cardiovascular magnetic resonance (LGE-CMR) has excellent specificity, sensitivity and diagnostic accuracy for differentiating between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (NICM). CMR first-pass myocardial perfusion imaging (perfusion-CMR) may also play role in distinguishing heart failure of ischemic and non-ischemic origins, although the utility of additional of stress perfusion imaging in such patients is unclear. The aim of this retrospective study was to assess whether the addition of adenosine stress perfusion imaging to LGE-CMR is of incremental value for differentiating ICM and NICM in patients with severe left ventricular systolic dysfunction (LVSD) of uncertain etiology. METHODS: We retrospectively identified 100 consecutive adult patients (median age 69 years (IQR 59-73)) with severe LVSD (mean LV EF 26.6 ± 7.0%) referred for perfusion-CMR to establish the underlying etiology of heart failure. The cause of heart failure was first determined on examination of CMR cine and LGE images in isolation. Subsequent examination of complete adenosine stress perfusion-CMR studies (cine, LGE and perfusion images) was performed to identify whether this altered the initial diagnosis. RESULTS: On LGE-CMR, 38 patients were diagnosed with ICM, 46 with NICM and 16 with dual pathology. With perfusion-CMR, there were 39 ICM, 44 NICM and 17 dual pathology diagnoses. There was excellent agreement in diagnoses between LGE-CMR and perfusion-CMR (κ 0.968, p<0.001). The addition of adenosine stress perfusion images to LGE-CMR altered the diagnosis in only two of the 100 patients. CONCLUSION: The addition of adenosine stress perfusion-CMR to cine and LGE-CMR provides minimal incremental diagnostic yield for determining the etiology of heart failure in patients with severe LVSD.


Assuntos
Adenosina/administração & dosagem , Cardiomiopatias/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Insuficiência Cardíaca/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Meglumina/administração & dosagem , Isquemia Miocárdica/diagnóstico por imagem , Imagem de Perfusão do Miocárdio/métodos , Compostos Organometálicos/administração & dosagem , Vasodilatadores/administração & dosagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Angiografia Coronária , Diagnóstico Diferencial , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda
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