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1.
Curr Biol ; 22(22): R953-6, 2012 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-23174297

RESUMO

Two recent studies describe mechanisms by which sexually dimorphic responses to pheromones in the nematode worm Caenorhabditis elegans are driven by differences in the balance of neural circuits that control attraction and repulsion behaviors.


Assuntos
Caenorhabditis elegans/fisiologia , Neurônios/fisiologia , Atrativos Sexuais/fisiologia , Comportamento Sexual Animal/fisiologia , Animais , Comportamento de Escolha/fisiologia , Conectoma , Feminino , Masculino
2.
BMJ Open ; 2(4)2012.
Artigo em Inglês | MEDLINE | ID: mdl-22858459

RESUMO

OBJECTIVES: Reducing emergency admissions is a priority for the NHS. A single hospital's emergency care system was reorganised with the principles of front-loaded investigations, integration of specialties, reduced duplication, earlier decision making by senior clinicians and a combined emergency assessment area. The authors relocated our Medical Assessment Unit into our emergency department in 2006. The authors evaluated changes in admissions and mortality before and after 2006, compared with other similar hospitals. DESIGN: Quasi-experimental before and after study using routinely collected data. SETTING AND PARTICIPANTS: 1 acute hospital in England, the intervention site, was compared with 23 other English hospitals between 2001 and 2009. OUTCOME MEASURES: Our outcome measures were hospital standardised mortality ratios (HSMRs) for non-elective admissions and standardised admission ratios (SARs). RESULTS: The authors observed a statistically and clinically significant decrease in HSMR and SAR. The intervention hospital had the lowest HSMR and SAR of all the hospitals in our sample. This was statistically significant, p=0.0149 and p=0.0002, respectively. CONCLUSION: Integrating emergency care in one location is associated with a meaningful reduction in mortality and emergency admissions to hospital.

3.
J Am Coll Cardiol ; 59(17): 1509-18, 2012 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-22405632

RESUMO

OBJECTIVES: This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). BACKGROUND: Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. METHODS: A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure-related hospitalization. RESULTS: The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). CONCLUSIONS: Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure-related hospitalization. (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy [TARGET] study); ISRCTN19717943).


Assuntos
Terapia de Ressincronização Cardíaca/mortalidade , Terapia de Ressincronização Cardíaca/métodos , Insuficiência Cardíaca/terapia , Ventrículos do Coração/diagnóstico por imagem , Idoso , Dispositivos de Terapia de Ressincronização Cardíaca , Causas de Morte , Ecocardiografia/métodos , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Método Simples-Cego , Volume Sistólico , Taxa de Sobrevida , Resultado do Tratamento , Reino Unido , Remodelação Ventricular/fisiologia
4.
Acta Radiol ; 51(4): 368-74, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20350244

RESUMO

BACKGROUND: Changes in diagnostic confidence are used as a measure of a test's efficacy. There are several methods for analyzing such data, but it is unclear which are most robust. PURPOSE: To compare analytical methods for assessing diagnostic confidence, applied to data from a prospective study of computed tomography (CT) for acute abdominal pain. MATERIAL AND METHODS: Changes in diagnostic confidence in an illustrative case study were evaluated using five methods: "Basic," "Retained diagnosis," "Omary," "Tsushima," and "Score-based." The case study was a randomized controlled trial of patients admitted to hospital for acute abdominal pain for whom immediate CT was not indicated, comparing "early" CT undertaken within 24 h of admission versus routine standard practice. Admitting surgeons recorded their diagnoses and confidences (5-point scale, 10-90%) both on admission and after 24 h. One- and two-sample t tests, and intention-to-treat and as-treated analyzes, were performed using all five analytic methods. RESULTS: In the case study, 118 patients were randomized to early CT (n=55) or standard practice (n=63). Mean (SD) diagnostic confidence increased between the two time points by 20.7 (25.2)% and 13.0 (24.9)%, respectively. Early CT showed increases in diagnostic confidence by all one-sample analyzes (all P<0.055). Compared with standard practice, early CT showed significant increases in diagnostic confidence on an a) as-treated basis when using Basic, Omary and Score-based analyzes (P<0.045), but not by the other two analytic methods, and b) intention-to-treat, only by Omary analysis. CONCLUSION: The method of analysis used to evaluate diagnostic confidence can influence conclusions about a test's efficacy. Methods incorporating the soundest analytical principles are recommended.


Assuntos
Abdome Agudo/diagnóstico por imagem , Tomografia Computadorizada por Raios X/normas , Tomada de Decisões , Erros de Diagnóstico , Humanos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estatística como Assunto
5.
Liver Transpl ; 16(3): 279-88, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20209638

RESUMO

The selection of patients with hepatocellular carcinoma for liver transplantation is currently based on the size and number of tumors to minimize the risk of recurrence. These criteria measure tumor bulk but may not reflect tumor behavior accurately. A biological marker of tumor behavior could aid with patient selection further. The aims of this study were to determine factors associated with a higher risk of tumor recurrence and to assess the role of tumor proliferation status with respect to recurrence following transplantation. Pathological data on 67 patients who underwent transplantation for hepatocellular carcinoma were reviewed, and tumor proliferation was assessed by minichromosome maintenance protein-2 (MCM-2) and cyclin A expression. A Cox regression analysis of factors related to tumor recurrence and overall survival was carried out. Recurrence-free survival was assessed according to compatibility with selection criteria, vascular invasion, and proliferation status. Tumor size, vascular invasion, and highest MCM-2 expression were associated with tumor recurrence by multivariate analysis (P < 0.02). Recurrence-free survival was significantly better for those patients without vascular invasion, those who were within the Milan, University of California San Francisco (UCSF), or Up-to-Seven selection criteria, and those with lower expression of MCM-2. In conclusion, tumors meeting the Milan, UCSF, or Up-to-Seven selection criteria had a lower rate of recurrence following liver transplantation. Vascular invasion and tumor proliferation status were associated with the risk of recurrence independently of tumor size. Biopsy of larger tumors to assess proliferative activity could identify those at lower risk of recurrence who could also benefit from liver transplantation.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Proliferação de Células , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Recidiva Local de Neoplasia/epidemiologia , Adolescente , Adulto , Idoso , Biópsia , Carcinoma Hepatocelular/irrigação sanguínea , Proteínas de Ciclo Celular/metabolismo , Criança , Pré-Escolar , Ciclina A/metabolismo , Feminino , Humanos , Fígado/metabolismo , Fígado/patologia , Neoplasias Hepáticas/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo , Análise Multivariada , Neovascularização Patológica/patologia , Proteínas Nucleares/metabolismo , Seleção de Pacientes , Alocação de Recursos , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Obtenção de Tecidos e Órgãos , Adulto Jovem
6.
Acta Neurochir (Wien) ; 152(6): 953-7, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20069321

RESUMO

PURPOSE: Numerous statistical methods have been utilised to generate predictive models that identify clinical and biochemical parameters of prognostic value following traumatic brain injury. While these methods provide an accurate statistical description between these variables and outcome, they are difficult to interpret intuitively. Hierarchical log linear analysis can be utilised to present the complex interactions between these variables and outcome visually. METHODS: We compiled a database of 327 traumatic brain injury patients, their admission blood parameters, clinical admission parameters, and 6-month Glasgow Outcome Score. Seven variables (age, injury severity, Glasgow Coma Score, glucose, albumin, haemoglobin, white cell count) that correlated with outcome in a univariate analysis and two further variables, included on the basis of biological plausibility, (abnormal clotting and magnesium) were used to derive and present a hierarchical log linear model. RESULTS: Seventeen (out of an original forty-five possible) inter-relationships between the chosen variables were identified as remaining in the hierarchical log linear model. This data is presented pictorially in a hierarchy demonstrating the directness of the statistical association between each of the variables and dichotomised outcome. Four variables within the hierarchical log linear model (age, raised serum glucose, low haemoglobin, Glasgow Coma Score) had a direct independent statistical relationship with outcome. The remaining five variables only had a statistical relationship with outcome via at least one other variable. CONCLUSIONS: Hierarchical log linear analysis allows the presentation of multivariate, categorical data sets in a pictorial and more easily interpretable fashion.


Assuntos
Análise Química do Sangue/estatística & dados numéricos , Lesões Encefálicas/diagnóstico , Complicações Pós-Operatórias/sangue , APACHE , Escala de Coma de Glasgow/estatística & dados numéricos , Escala de Resultado de Glasgow/estatística & dados numéricos , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Modelos Lineares , Auditoria Médica , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Retrospectivos , Estatística como Assunto , Reino Unido
7.
N Engl J Med ; 359(18): 1873-84, 2008 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-18971490

RESUMO

BACKGROUND: Studies involving adults and children being treated in intensive care units indicate that insulin therapy and glucose control may influence survival. Hyperglycemia in very-low-birth-weight infants is also associated with morbidity and mortality. This international randomized, controlled trial aimed to determine whether early insulin replacement reduced hyperglycemia and affected outcomes in such neonates. METHODS: In this multicenter trial, we assigned 195 infants to continuous infusion of insulin at a dose of 0.05 U per kilogram of body weight per hour with 20% dextrose support and 194 to standard neonatal care on days 1 to 7. The efficacy of glucose control was assessed by continuous glucose monitoring. The primary outcome was mortality at the expected date of delivery. The study was discontinued early because of concerns about futility with regard to the primary outcome and potential harm. RESULTS: As compared with infants in the control group, infants in the early-insulin group had lower mean (+/-SD) glucose levels (6.2+/-1.4 vs. 6.7+/-2.2 mmol per liter [112+/-25 vs. 121+/-40 mg per deciliter], P=0.007). Fewer infants in the early-insulin group had hyperglycemia for more than 10% of the first week of life (21% vs. 33%, P=0.008). The early-insulin group had significantly more carbohydrate infused (51+/-13 vs. 43+/-10 kcal per kilogram per day, P<0.001) and less weight loss in the first week (standard-deviation score for change in weight, -0.55+/-0.52 vs. -0.70+/-0.47; P=0.006). More infants in the early-insulin group had episodes of hypoglycemia (defined as a blood glucose level of <2.6 mmol per liter [47 mg per deciliter] for >1 hour) (29% in the early-insulin group vs. 17% in the control group, P=0.005), and the increase in hypoglycemia was significant in infants with birth weights of more than 1 kg. There were no differences in the intention-to-treat analyses for the primary outcome (mortality at the expected date of delivery) and the secondary outcome (morbidity). In the intention-to-treat analysis, mortality at 28 days was higher in the early-insulin group than in the control group (P=0.04). CONCLUSIONS: Early insulin therapy offers little clinical benefit in very-low-birth-weight infants. It reduces hyperglycemia but may increase hypoglycemia (Current Controlled Trials number, ISRCTN78428828.)


Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Recém-Nascido de muito Baixo Peso/sangue , Insulina/uso terapêutico , Glicemia/análise , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Mortalidade Infantil , Recém-Nascido , Infusões Intravenosas , Insulina/efeitos adversos , Masculino , Resultado do Tratamento
8.
Acad Radiol ; 15(5): 584-92, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18423315

RESUMO

RATIONALE AND OBJECTIVES: The ability of a test to influence diagnostic confidence is used as a measure of its efficacy. Our aim was to compare analytic methods that evaluate changes in confidence. MATERIALS AND METHODS: The approaches compared were "basic," "retained diagnoses," "Omary," "Tsushima," and "score-based" methods. For illustration, data from a clinical study assessing changes in diagnostic confidence (0%-100%) before and after abdominopelvic computed tomography (CT) in patients with acute abdominal pain were used. RESULTS: The basic, retained diagnoses and Omary methods all ignore whether the test yields a correct diagnosis (confident, but incorrect, diagnoses are regarded positively). Although the Tsushima method takes some account of diagnostic accuracy, all misdiagnoses are considered equal. The score-based method addresses some of the fundamental limitations in the other analytical methods, such as diagnostic accuracy and the varying nature of different misdiagnoses. In the case study, mean (SD) diagnostic confidence for the cohort as a whole (n = 62) increased following CT: 50.7% (20.8%) to 73.2% (20.9%). Pretest diagnoses were changed following CT in 43% (27 of 62) of patients. Pretest diagnoses proved to be incorrect in 52% (32 of 62), and post-test diagnoses incorrect in as many as 19% (12 of 62) of patients. All five analytic methods indicated a positive contribution for CT (all P < or = .003). CONCLUSION: Although our illustrative case study revealed no consequential differences across the five methods, there remain substantial differences in the fundamental principles underlying them that should affect choice of analytic method when assessing diagnostic confidence.


Assuntos
Abdome Agudo/diagnóstico por imagem , Radiografia Abdominal , Tomografia Computadorizada por Raios X/normas , Tomada de Decisões , Erros de Diagnóstico , Humanos
9.
Liver Transpl ; 13(12): 1694-702, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18044728

RESUMO

Renal impairment is common in patients after liver transplantation and is attributable in large part to the use of calcineurin inhibitor (CNI)-based immunosuppression. We sought to determine whether conversion to sirolimus-based immunosuppression was associated with improved renal function. In a single-center, randomized, controlled trial, 30 patients at least 6 months post liver transplantation were randomized to remain on CNI-based immunosuppression or to switch to sirolimus-based immunosuppression. The primary outcome measure was change in measured glomerular filtration rate (GFR) between baseline and 12 months. Of 30 patients randomized, 3 were withdrawn at randomization, leaving 14 patients on CNI and 13 on sirolimus. There was a significant improvement in delta GFR following conversion to sirolimus at 3 months (7.7 mL/minute/1.73 m2; 95% confidence interval, 3.5-11.9) and 1 yr (6.1 mL/minute/1.73 m2; 95% confidence interval, 0.9-11.4). The difference in absolute GFR between the 2 study groups was significant at 3 months (P=0.02), but not at 12 months (P=0.07). The principal adverse events following conversion were the development of skin rash (9 of 13 patients, 69%) and mouth ulcers (5 of 13 patients, 38%). Two patients developed acute rejection at 2 and 3 months following conversion, 1 in association with low sirolimus levels and 1 having stopped the drug inadvertently. In conclusion, overall, this study suggests that conversion to sirolimus immunosuppression is associated with a modest improvement in renal function. Side effects were common, but tolerable in most patients and controlled with dose reduction.


Assuntos
Inibidores de Calcineurina , Ciclosporina/efeitos adversos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/efeitos adversos , Nefropatias/induzido quimicamente , Transplante de Fígado , Sirolimo/efeitos adversos , Tacrolimo/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Nefropatias/sangue , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Fatores de Tempo , Resultado do Tratamento
10.
Stat Med ; 26(27): 4939-57, 2007 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-17582801

RESUMO

This paper addresses two main questions: first, why should Bayesian and other innovative, data-dependent design models be put into practice and, secondly, given the past dearth of actual applications, how might one example of such a design be implemented in a genuine example trial? Clinical trials amalgamate theory, practice and ethics, but this last point has become relegated to the background, rather than taking often a more appropriate primary role. Trial practice has evolved but has its roots in R. A. Fisher's randomized agricultural field trials of the 1920s. Reasons for, and consequences of, this are discussed from an ethical standpoint, drawing on an under-used dichotomy introduced by French authors Lellouch and Schwartz (Int. Statist. Rev. 1971; 39:27-36). Plenty of ethically motivated designs for trials, including Bayesian designs have been proposed, but have found little application thus far. One reason for this is a lack of awareness of such alternative designs among trialists, while another reason is a lack of user-friendly software to allow study simulations. To encourage implementation, a new C++ program called 'Daniel' is introduced, offering much potential to assist the design of today's randomized controlled trials. Daniel evaluates a particular decision-theoretic method suitable for coping with either two or three Bernoulli response treatments with input features allowing user-specified choices of: patient horizon (number to be treated before and after the comparative stages of the trial); an arbitrary fixed trial truncation size (to allow ready comparison with traditional designs or to cope with practical constraints); anticipated success rates and a measure of their uncertainty (a matter ignored in standard power calculations); and clinically relevant, and irrelevant, differences in treatment effect sizes. Error probabilities and expected trial durations can be thoroughly explored via simulation, it being better by far to harm 'computer patients' instead of real ones. Suppose the objective in a clinical trial is to select between two treatments using a maximum horizon of 500 patients, when the truly superior treatment is expected to yield a 40 per cent success rate, but is believed to really range between 20 and 60 per cent. Simulation studies show that to detect a clinically relevant, absolute difference of 10 per cent between treatments, simulation studies show the decision-theoretic procedure would treat a mean 68 pairs of patients (SD 37) before correctly identifying the better treatment 96.7 per cent of the time, an error rate of 3.3 per cent. Having made a recommendation based on these patients, the remaining, on average 364 individuals, could either be given the indicated treatment, knowing its choice is optimal for the chosen horizon, or, alternatively, they could be entered into another, separate clinical trial. For comparison, a fixed sample size trial, with standard 5 per cent level of significance and 80 per cent power to detect a 10 per cent difference, requires treating over 700 patients in two groups, with the half allocated to inferior treatment considerably outnumbering the 68 expected under the decision-theoretic design, and the overall number simply too high for realistic application. In brief, the keys to answering the above 'why?' and 'how?' questions are ethics and software, respectively. Wider implications, both pros and cons, of implementing the particular method described will be discussed, with the overall conclusion that, where appropriate, clinical trials are now ready to undergo modernization from the agricultural age to the information age.


Assuntos
Teorema de Bayes , Teoria da Decisão , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Software , Cuidados Críticos/métodos , Tomada de Decisões/ética , Humanos , Intubação/métodos , Oxigênio/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto/ética
11.
Int J Antimicrob Agents ; 30(1): 78-82, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17475448

RESUMO

We questioned 62 dermatology outpatients with atopic eczema and Staphylococcus aureus colonisation regarding their use of topical preparations containing fusidic acid during the previous 6 months as well as the pattern of any such use. Recent exposure to topical fusidic acid was significantly correlated with the presence of fusidic acid-resistant S. aureus (FRSA) (P=0.04). There was also a significant trend towards increasing FRSA carriage with increased duration of use. Short courses of 2 weeks or less did not appear to change the FRSA profile compared with non-exposure, and intermittent usage appeared to be the most detrimental, although subgroup sizes were small. Our study cautions against prolonged or intermittent use of fusidic acid-containing products in patients with eczema.


Assuntos
Dermatite Atópica/microbiologia , Farmacorresistência Bacteriana , Ácido Fusídico/farmacologia , Ácido Fusídico/uso terapêutico , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Administração Tópica , Portador Sadio/microbiologia , Criança , Pré-Escolar , Dermatite Atópica/complicações , Feminino , Ácido Fusídico/administração & dosagem , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Staphylococcus aureus/isolamento & purificação
12.
Am J Transplant ; 5(10): 2496-503, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16162200

RESUMO

Maintenance immunosuppression with calcineurin inhibitors (CNIs) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. We aimed to assess whether conversion to sirolimus-based immunosuppression would affect the progression of renal impairment. In this single center, randomized controlled trial, 40 renal transplant recipients between 6 months and 8 years post-transplant were randomly assigned to remain on their CNI (cyclosporin or tacrolimus) or to switch to sirolimus. The primary outcome measure was change in glomerular filtration rate (GFR) measurement at 12 months. Analysis was by intention-to-treat. Of the 40 patients randomized, 2 patients never took the study drugs and were excluded, leaving 19 patients per group. There was a significant change in GFR at 12 months following conversion to sirolimus (12.9 mL/min, 95% CI 6.1-19.7; p < 0.001). Following conversion, the principal adverse events were the development of rashes (68%), particularly acne, and mouth ulcers (32%). No patient in either group experienced an acute rejection episode. In renal transplant recipients, a change in maintenance therapy from CNIs to sirolimus is associated with significant improvement in GFR at 12 months.


Assuntos
Inibidores de Calcineurina , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Sirolimo/administração & dosagem , Adulto , Idoso , Pressão Sanguínea , Radioisótopos de Cromo/uso terapêutico , Ácido Edético/química , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Tolerância Imunológica , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Rim/patologia , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Projetos de Pesquisa , Fatores de Tempo , Resultado do Tratamento
13.
Arch Intern Med ; 164(22): 2459-64, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15596636

RESUMO

BACKGROUND: Increasing evidence suggests renal involvement in hypertension-related cardiovascular and cerebrovascular complications. To assess this role of renal function in more detail, we studied the evolution of renal function and the relationship of renal function with mortality and morbidity in the Intervention as a Goal in Hypertension Treatment (INSIGHT) study. METHODS: The INSIGHT study was a double-blind, randomized, multicenter trial in patients with hypertension and at least 1 additional cardiovascular risk factor. Treatment consisted of nifedipine gastrointestinal therapeutic system, 30 mg/d, or hydrochlorothiazide-amiloride (25 mg/d of hydrochlorothiazide and 2.5 mg/d of amiloride hydrochloride). Primary outcome was a composite of cardiovascular death, myocardial infarction, heart failure, and stroke. Renal function was assessed by measuring creatinine clearance, serum creatinine level, and serum uric acid level and by the presence of proteinuria. RESULTS: Creatinine clearance fell more in nifedipine recipients than in hydrochlorothiazide-amiloride recipients. Renal insufficiency developed in 2% of nifedipine recipients and 5% of hydrochlorothiazide-amiloride recipients. Primary outcomes occurred in 15% of patients with increased serum creatinine levels and 6% of patients with normal levels (odds ratio [OR] 2.89; 95% confidence interval [CI], 1.92-4.36; P<.001). Primary outcomes were more likely in patients with low creatinine clearance (<60 mL/min) than in those with higher clearances (9% vs 5%, respectively [OR, 1.51, 95%CI, 1.22-1.88; P<.001]). CONCLUSIONS: Renal function is an important predictor of risk in hypertensive patients at high risk. Antihypertensive treatment with a long-acting dihydropyridine calcium channel blocker may better preserve renal function than would treatment with diuretics.


Assuntos
Hipertensão/fisiopatologia , Rim/fisiopatologia , Idoso , Amilorida/uso terapêutico , Doenças Cardiovasculares/etiologia , Creatinina/sangue , Método Duplo-Cego , Feminino , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Nifedipino/uso terapêutico , Insuficiência Renal/prevenção & controle , Fatores de Risco , Vasodilatadores/uso terapêutico
14.
Physiol Behav ; 78(3): 395-401, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12676274

RESUMO

The aim of two studies was to examine both between-subjects and within-subjects associations between daily amounts of physical activity and sleep in the home environment. Study 1 examined self-reported exercise durations and sleep diaries for 105 consecutive days in 31 college students who were normal sleepers. Between-subjects associations of mean exercise with mean sleep were assessed with Spearman rank-order correlations. Within-subjects correlations were determined across 105 days, and by comparing sleep on the 11 most active vs. the 11 least active days. Study 2 examined 71 physically active adults (n=38 ages 18-30 years, and n=33 ages 60-75 years), the majority of whom were normal sleepers. Over seven consecutive days, physical activity was assessed via actigraphy and a diary-derived estimate of energy expenditure, and sleep was assessed via actigraphy and sleep diaries. Between-subjects associations of mean physical activity with mean sleep were assessed with partial correlations, controlling for age. Within-subjects associations were assessed with ANCOVAs, with daily physical activity serving as the covariate, and by comparing sleep on the most active vs. the least active day. No significant within-subjects associations between physical activity and sleep were found in the main analyses of either study. Two small, but significant, between-subjects correlations between different physical activity measures and subjective sleep were found in Study 2. These results fail to support epidemiologic data on the value of exercise for sleep, but are consistent with experimental evidence showing only modest effects of exercise on sleep.


Assuntos
Metabolismo Energético , Esforço Físico/fisiologia , Sono/fisiologia , Adolescente , Adulto , Idoso , Exercício Físico/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estatística como Assunto
16.
Hypertension ; 41(3): 431-6, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12623939

RESUMO

To investigate the impact of treatment on cardiovascular mortality and morbidity, we assessed outcomes in patients with hypertension and diabetes who received co-amilozide or nifedipine in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension. Participants had to be 55 to 80 years of age, with hypertension (> or =150/95 or > or =160 mm Hg) and at least one additional cardiovascular risk factor. Patients received 30 mg nifedipine once daily or co-amilozide (25 mg hydrochlorothiazide and 2.5 mg amiloride) daily. Doses were doubled if target blood pressures (<140/90 mm Hg) were not achieved. Primary (composite of cardiovascular death, myocardial infarction, heart failure, and stroke) and secondary outcomes (composite of primary outcomes, including all-cause mortality and death from vascular and nonvascular causes) were assessed by means of intent-to-treat analyses. There was no significant difference in the incidence of primary outcomes between nifedipine-treated and co-amilozide-treated patients with diabetes at baseline (n=1302) (8.3% versus 8.4%; relative risk, 0.99, 95% CI, 0.69 to 1.42; P=1.00). A significant benefit for nifedipine-treated patients was seen for the composite secondary outcome (14.2% versus 18.7%; relative risk, 0.76, 95% CI, 0.59 to 0.97; P=0.03). Among patients without diabetes at baseline (n=5019), there was a significant difference in the incidence of new diabetes (nifedipine 4.3% versus co-amilozide 5.6%, P=0.023). Nifedipine GITS once daily is as effective as diuretic therapy in reducing cardiovascular complications in hypertensive diabetics. Nifedipine-treated patients were also less likely to have diabetes or have secondary events (a composite of all-cause mortality, death from a vascular cause, and death from a nonvascular cause) than co-amilozide recipients. Our results suggest that nifedipine could be considered as first-line therapy for hypertensive diabetics.


Assuntos
Amilorida/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Complicações do Diabetes , Diuréticos/uso terapêutico , Hidroclorotiazida/uso terapêutico , Hipertensão/tratamento farmacológico , Nifedipino/uso terapêutico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus/epidemiologia , Combinação de Medicamentos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/complicações , Hipertensão/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Objetivos Organizacionais , Resultado do Tratamento
17.
Behav Sleep Med ; 1(4): 213-26, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15602801

RESUMO

This study tested whether a newly designed enhanced evening light therapy was well tolerated and effective in relieving symptoms of Advanced, Sleep Phase Syndrome (ASPS). Participants with self-reported ASPS symptoms were 47 older adults (21 men and 26 women, age 60-86). After baseline, participants underwent 28 consecutive days of either dim or enhanced intensity light treatment for 2-3 hr in the evening. Enhanced evening light (approximately 265 lux) exposure was no more effective than a placebo dim light (approximately 2 lux) at alleviating advanced sleep phase as measured by actigraphically recorded sleep and urinary 6-sulphatoxymelatonin (aMT6s) excretion patterns. Participants receiving the enhanced light reported subjective benefit and a significant delay in sleep onset as compared to the placebo. Although compliance was good and the new enhanced evening light therapy design was well tolerated, the benefits were statistically equivocal.


Assuntos
Ritmo Circadiano/fisiologia , Fototerapia/métodos , Transtornos do Sono-Vigília/terapia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
18.
BMJ ; 325(7377): 1387, 2002 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-12480851

RESUMO

OBJECTIVES: To evaluate the impact of early abdominopelvic computed tomography in patients with acute abdominal pain of unknown cause on length of hospital stay and accuracy of diagnosis. DESIGN: Randomised, prospective controlled trial. SETTING: Teaching hospital in England. PARTICIPANTS: 120 patients admitted with acute abdominal pain for which no immediate surgical intervention or computed tomography was indicated. INTERVENTION: 55 participants were prospectively randomised to early computed tomography (within 24 hours of admission) and 65 to standard practice (radiological investigations as indicated). MAIN OUTCOME MEASURES: Length of hospital stay, accuracy of diagnosis, and, owing to a possible effect on inpatient mortality, deaths during the study. RESULTS: Early computed tomography reduced the length of hospital stay by 1.1 days (geometric mean 5.3 days (range 1 to 31) v 6.4 days (1 to 60)), but the difference was non-significant (95% confidence interval, 8% shorter stay to 56% longer stay, P=0.17). Early computed tomography missed significantly fewer serious diagnoses. Seven inpatients in the standard practice arm died. Only 50% (59 of 118) of diagnoses on admission were correct at follow up at 6 months, but this improved to 76% (90) of diagnoses after 24 hours. CONCLUSIONS: Early abdominopelvic computed tomography for acute abdominal pain may reduce mortality and length of hospital stay. It can also identify unforeseen conditions and potentially serious complications.


Assuntos
Dor Abdominal/diagnóstico por imagem , Dor Abdominal/etiologia , Adulto , Idoso , Humanos , Tempo de Internação , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas
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