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1.
Medicine (Baltimore) ; 98(44): e17760, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689835

RESUMO

BACKGROUND: The risk of recurrent herniation after lumbar discectomy is highest during the first postoperative year. The purpose of this study was to determine whether implantation of a bone-anchored annular closure device (ACD) following limited lumbar discectomy reduced the risk of recurrent herniation and complications during the first year of follow-up compared to limited lumbar discectomy alone (Controls) and whether this risk was influenced by patient characteristics. METHODS: In this randomized multicenter trial, patients with symptomatic lumbar disc herniation and with a large annular defect following limited lumbar discectomy were randomized to bone-anchored ACD or Control groups. The risks of symptomatic reherniation, reoperation, and device- or procedure-related serious adverse events were reported over 1 year of follow-up. RESULTS: Among 554 patients (ACD 276; Control 278), 94% returned for 1-year follow-up. Bone-anchored ACD resulted in lower risks of symptomatic reherniation (8.4% vs. 17.3%, P = .002) and reoperation (6.7% vs. 12.9%, P = .015) versus Controls. Device- or procedure-related serious adverse events through 1 year were reported in 7.1% of ACD patients and 13.9% of Controls (P = .009). No baseline patient characteristic significantly influenced these risks. CONCLUSIONS: Among patients with large annular defects following limited lumbar discectomy, additional implantation with a bone-anchored ACD lowered the risk of symptomatic reherniation and reoperation over 1 year follow-up. Device- or procedure-related serious adverse events occurred less frequently in the ACD group. These conclusions were not influenced by patient characteristics. ClinicalTrials.gov (NCT01283438).


Assuntos
Prótese Ancorada no Osso , Discotomia/instrumentação , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Prevenção Secundária/métodos , Adulto , Discotomia/métodos , Feminino , Humanos , Masculino , Recidiva , Reoperação/estatística & dados numéricos , Resultado do Tratamento
2.
BMJ ; 366: l4697, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31434641

RESUMO

OBJECTIVE: To assess effects of increasing omega-3, omega-6, and total polyunsaturated fatty acids (PUFA) on diabetes diagnosis and glucose metabolism. DESIGN: Systematic review and meta-analyses. DATA SOURCES: Medline, Embase, Cochrane CENTRAL, WHO International Clinical Trials Registry Platform, Clinicaltrials.gov, and trials in relevant systematic reviews. ELIGIBILITY CRITERIA: Randomised controlled trials of at least 24 weeks' duration assessing effects of increasing α-linolenic acid, long chain omega-3, omega-6, or total PUFA, which collected data on diabetes diagnoses, fasting glucose or insulin, glycated haemoglobin (HbA1c), and/or homoeostatic model assessment for insulin resistance (HOMA-IR). DATA SYNTHESIS: Statistical analysis included random effects meta-analyses using relative risk and mean difference, and sensitivity analyses. Funnel plots were examined and subgrouping assessed effects of intervention type, replacement, baseline risk of diabetes and use of antidiabetes drugs, trial duration, and dose. Risk of bias was assessed with the Cochrane tool and quality of evidence with GRADE. RESULTS: 83 randomised controlled trials (mainly assessing effects of supplementary long chain omega-3) were included; 10 were at low summary risk of bias. Long chain omega-3 had little or no effect on likelihood of diagnosis of diabetes (relative risk 1.00, 95% confidence interval 0.85 to 1.17; 58 643 participants, 3.7% developed diabetes) or measures of glucose metabolism (HbA1c mean difference -0.02%, 95% confidence interval -0.07% to 0.04%; plasma glucose 0.04, 0.02 to 0.07, mmol/L; fasting insulin 1.02, -4.34 to 6.37, pmol/L; HOMA-IR 0.06, -0.21 to 0.33). A suggestion of negative outcomes was observed when dose of supplemental long chain omega-3 was above 4.4 g/d. Effects of α-linolenic acid, omega-6, and total PUFA on diagnosis of diabetes were unclear (as the evidence was of very low quality), but little or no effect on measures of glucose metabolism was seen, except that increasing α-linolenic acid may increase fasting insulin (by about 7%). No evidence was found that the omega-3/omega-6 ratio is important for diabetes or glucose metabolism. CONCLUSIONS: This is the most extensive systematic review of trials to date to assess effects of polyunsaturated fats on newly diagnosed diabetes and glucose metabolism, including previously unpublished data following contact with authors. Evidence suggests that increasing omega-3, omega-6, or total PUFA has little or no effect on prevention and treatment of type 2 diabetes mellitus. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017064110.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/prevenção & controle , Gorduras Insaturadas na Dieta/uso terapêutico , Prevenção Primária/métodos , Prevenção Secundária/métodos , Adulto , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Suplementos Nutricionais , Jejum/sangue , Ácidos Graxos Ômega-3/uso terapêutico , Ácidos Graxos Ômega-6/uso terapêutico , Ácidos Graxos Insaturados/uso terapêutico , Feminino , Hemoglobina A Glicada/análise , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Lancet ; 394(10199): 672-683, 2019 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-31448738

RESUMO

BACKGROUND: A fixed-dose combination therapy (polypill strategy) has been proposed as an approach to reduce the burden of cardiovascular disease, especially in low-income and middle-income countries (LMICs). The PolyIran study aimed to assess the effectiveness and safety of a four-component polypill including aspirin, atorvastatin, hydrochlorothiazide, and either enalapril or valsartan for primary and secondary prevention of cardiovascular disease. METHODS: The PolyIran study was a two-group, pragmatic, cluster-randomised trial nested within the Golestan Cohort Study (GCS), a cohort study with 50 045 participants aged 40-75 years from the Golestan province in Iran. Clusters (villages) were randomly allocated (1:1) to either a package of non-pharmacological preventive interventions alone (minimal care group) or together with a once-daily polypill tablet (polypill group). Randomisation was stratified by three districts (Gonbad, Aq-Qala, and Kalaleh), with the village as the unit of randomisation. We used a balanced randomisation algorithm, considering block sizes of 20 and balancing for cluster size or natural log of the cluster size (depending on the skewness within strata). Randomisation was done at a fixed point in time (Jan 18, 2011) by statisticians at the University of Birmingham (Birmingham, UK), independent of the local study team. The non-pharmacological preventive interventions (including educational training about healthy lifestyle-eg, healthy diet with low salt, sugar, and fat content, exercise, weight control, and abstinence from smoking and opium) were delivered by the PolyIran field visit team at months 3 and 6, and then every 6 months thereafter. Two formulations of polypill tablet were used in this study. Participants were first prescribed polypill one (hydrochlorothiazide 12·5 mg, aspirin 81 mg, atorvastatin 20 mg, and enalapril 5 mg). Participants who developed cough during follow-up were switched by a trained study physician to polypill two, which included valsartan 40 mg instead of enalapril 5 mg. Participants were followed up for 60 months. The primary outcome-occurrence of major cardiovascular events (including hospitalisation for acute coronary syndrome, fatal myocardial infarction, sudden death, heart failure, coronary artery revascularisation procedures, and non-fatal and fatal stroke)-was centrally assessed by the GCS follow-up team, who were masked to allocation status. We did intention-to-treat analyses by including all participants who met eligibility criteria in the two study groups. The trial was registered with ClinicalTrials.gov, number NCT01271985. FINDINGS: Between Feb 22, 2011, and April 15, 2013, we enrolled 6838 individuals into the study-3417 (in 116 clusters) in the minimal care group and 3421 (in 120 clusters) in the polypill group. 1761 (51·5%) of 3421 participants in the polypill group were women, as were 1679 (49·1%) of 3417 participants in the minimal care group. Median adherence to polypill tablets was 80·5% (IQR 48·5-92·2). During follow-up, 301 (8·8%) of 3417 participants in the minimal care group had major cardiovascular events compared with 202 (5·9%) of 3421 participants in the polypill group (adjusted hazard ratio [HR] 0·66, 95% CI 0·55-0·80). We found no statistically significant interaction with the presence (HR 0·61, 95% CI 0·49-0·75) or absence of pre-existing cardiovascular disease (0·80; 0·51-1·12; pinteraction=0·19). When restricted to participants in the polypill group with high adherence, the reduction in the risk of major cardiovascular events was even greater compared with the minimal care group (adjusted HR 0·43, 95% CI 0·33-0·55). The frequency of adverse events was similar between the two study groups. 21 intracranial haemorrhages were reported during the 5 years of follow-up-ten participants in the polypill group and 11 participants in the minimal care group. There were 13 physician-confirmed diagnoses of upper gastrointestinal bleeding in the polypill group and nine in the minimal care group. INTERPRETATION: Use of polypill was effective in preventing major cardiovascular events. Medication adherence was high and adverse event numbers were low. The polypill strategy could be considered as an additional effective component in controlling cardiovascular diseases, especially in LMICs. FUNDING: Tehran University of Medical Sciences, Barakat Foundation, and Alborz Darou.


Assuntos
Fármacos Cardiovasculares/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Combinação de Medicamentos , Prevenção Secundária/métodos , Adulto , Idoso , Anticolesterolemiantes/administração & dosagem , Anti-Hipertensivos/administração & dosagem , Aspirina/administração & dosagem , Atorvastatina/administração & dosagem , Pressão Sanguínea/efeitos dos fármacos , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol/efeitos dos fármacos , Diabetes Mellitus/epidemiologia , Enalapril/administração & dosagem , Feminino , Humanos , Hidroclorotiazida/administração & dosagem , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/administração & dosagem , Valsartana/administração & dosagem
4.
Ther Umsch ; 76(2): 65-70, 2019 08.
Artigo em Alemão | MEDLINE | ID: mdl-31429395

RESUMO

Skin cancer - prevention and therapy Abstract. Skin cancers are increasing in western countries. Prevention consists mainly of primary (UV- protection) and secondary (early detection) prevention. Family physicians are often the first contact persons to evaluate the dignity of skin lesions of high-risk patients and help to perform the diagnosis. If skin cancer is detected early, surgical removal is highly likely to achieve complete cure and reduce the financial burden due to malignant skin tumors. Great progress has been made in the local and systemic therapy of skin tumors in recent years.


Assuntos
Prevenção Primária/métodos , Prevenção Secundária/métodos , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/prevenção & controle
5.
Expert Rev Clin Pharmacol ; 12(8): 771-780, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31269825

RESUMO

Introduction: The current approach of using only antiplatelet therapy for secondary prevention leaves a substantial risk of recurrent cardiovascular complications and mortality. Areas covered: In this manuscript, the role of coagulation in atherothrombosis is reviewed, as well as the impact of vascular doses of rivaroxaban on major cardiovascular outcomes and major adverse limb events. Expert opinion: In COMPASS, among patients with coronary heart disease and/or peripheral artery disease, compared to aspirin, the addition of rivaroxaban 2.5 mg twice daily to aspirin, significantly reduced the risk of major atherosclerotic outcomes, cardiovascular death and death for any cause, with a significant increase in the risk of major bleeding, but not fatal or intracranial bleedings. Preclinical data strongly suggest that rivaroxaban exerts vascular protection through different mechanisms, including improvement of endothelial functionality and fibrinolytic activity at endothelium, anti-inflammatory properties, and platelet-dependent thrombin generation. All these data indicate that among patients with atherosclerotic vascular disease, the addition of rivaroxaban 2.5 mg may provide further vascular protection.


Assuntos
Aterosclerose/prevenção & controle , Inibidores do Fator Xa/administração & dosagem , Rivaroxabana/administração & dosagem , Animais , Aspirina/administração & dosagem , Aterosclerose/patologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Quimioterapia Combinada , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/farmacologia , Hemorragia/induzido quimicamente , Humanos , Rivaroxabana/efeitos adversos , Rivaroxabana/farmacologia , Prevenção Secundária/métodos
6.
Lancet ; 394(10202): 929-938, 2019 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-31327563

RESUMO

BACKGROUND: Primaquine is the only widely used drug that prevents Plasmodium vivax malaria relapses, but adherence to the standard 14-day regimen is poor. We aimed to assess the efficacy of a shorter course (7 days) of primaquine for radical cure of vivax malaria. METHODS: We did a randomised, double-blind, placebo-controlled, non-inferiority trial in eight health-care clinics (two each in Afghanistan, Ethiopia, Indonesia, and Vietnam). Patients (aged ≥6 months) with normal glucose-6-phosphate dehydrogenase (G6PD) and presenting with uncomplicated vivax malaria were enrolled. Patients were given standard blood schizontocidal treatment and randomly assigned (2:2:1) to receive 7 days of supervised primaquine (1·0 mg/kg per day), 14 days of supervised primaquine (0·5 mg/kg per day), or placebo. The primary endpoint was the incidence rate of symptomatic P vivax parasitaemia during the 12-month follow-up period, assessed in the intention-to-treat population. A margin of 0·07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen. This trial is registered at ClinicalTrials.gov (NCT01814683). FINDINGS: Between July 20, 2014, and Nov 25, 2017, 2336 patients were enrolled. The incidence rate of symptomatic recurrent P vivax malaria was 0·18 (95% CI 0·15 to 0·21) recurrences per person-year for 935 patients in the 7-day primaquine group and 0·16 (0·13 to 0·18) for 937 patients in the 14-day primaquine group, a difference of 0·02 (-0·02 to 0·05, p=0·3405). The incidence rate for 464 patients in the placebo group was 0·96 (95% CI 0·83 to 1·08) recurrences per person-year. Potentially drug-related serious adverse events within 42 days of starting treatment were reported in nine (1·0%) of 935 patients in the 7-day group, one (0·1%) of 937 in the 14-day group and none of 464 in the control arm. Four of the serious adverse events were significant haemolysis (three in the 7-day group and one in the 14-day group). INTERPRETATION: In patients with normal G6PD, 7-day primaquine was well tolerated and non-inferior to 14-day primaquine. The short-course regimen might improve adherence and therefore the effectiveness of primaquine for radical cure of P vivax malaria. FUNDING: UK Department for International Development, UK Medical Research Council, UK National Institute for Health Research, and the Wellcome Trust through the Joint Global Health Trials Scheme (MR/K007424/1) and the Bill & Melinda Gates Foundation (OPP1054404).


Assuntos
Antimaláricos/administração & dosagem , Malária Vivax/tratamento farmacológico , Primaquina/administração & dosagem , Adolescente , Adulto , Antimaláricos/efeitos adversos , Antimaláricos/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Esquema de Medicação , Estudos de Equivalência como Asunto , Feminino , Seguimentos , Humanos , Malária Vivax/parasitologia , Masculino , Adesão à Medicação/estatística & dados numéricos , Parasitemia/tratamento farmacológico , Parasitemia/parasitologia , Plasmodium vivax/isolamento & purificação , Primaquina/efeitos adversos , Primaquina/uso terapêutico , Recidiva , Prevenção Secundária/métodos , Adulto Jovem
7.
J Stroke Cerebrovasc Dis ; 28(9): 2363-2375, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31281110

RESUMO

The prevalence of atrial fibrillation (AF), the most common cardiac arrhythmia, increases with age, predisposing elderly patients to an increased risk of embolic stroke. With an increasingly aged population the number of people who experience a stroke every year, overall global burden of stroke, and numbers of stroke survivors and related deaths continue to increase. Anticoagulation with vitamin K antagonists (VKAs) reduces the risk of ischemic stroke in patients with AF; however, increased bleeding risk is well documented, particularly in the elderly. Consequently, VKAs have been underused in the elderly. Alternative anticoagulants may offer a safer choice, particularly in patients who have experienced previous stroke. The aim of this narrative review is to examine available evidence for the effective treatment of patients with AF and previous cerebral vascular events with non-VKA oral anticoagulants, including the most appropriate time to start or reinitiate treatment after a stroke, systemic embolism, or clinically relevant bleed. For patients with AF treated with oral anticoagulants it is important to balance increased protection against future stroke/systemic embolism and reduced risk of major bleeding events. For patients with AF who have previously experienced a cerebrovascular event, the use of oral anticoagulants alone also appears more effective than low-molecular weight heparin (LMWH) alone or LMWH followed by oral anticoagulants. Available data suggest that significant reduction in stroke, symptomatic cerebral bleeding, and major extracranial bleeding within 90 days from acute stroke can be achieved if oral anticoagulation is initiated at 4-14 days from stroke onset.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Prevenção Secundária/métodos , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Anticoagulantes/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Esquema de Medicação , Humanos , Hemorragias Intracranianas/induzido quimicamente , Hemorragias Intracranianas/epidemiologia , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do Tratamento
8.
BMJ ; 365: l1800, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31335316

RESUMO

OBJECTIVE: To determine whether extending initial prednisolone treatment from eight to 16 weeks in children with idiopathic steroid sensitive nephrotic syndrome improves the pattern of disease relapse. DESIGN: Double blind, parallel group, phase III randomised placebo controlled trial, including a cost effectiveness analysis. SETTING: 125 UK National Health Service district general hospitals and tertiary paediatric nephrology centres. PARTICIPANTS: 237 children aged 1-14 years with a first episode of steroid sensitive nephrotic syndrome. INTERVENTIONS: Children were randomised to receive an extended 16 week course of prednisolone (total dose 3150 mg/m2) or a standard eight week course of prednisolone (total dose 2240 mg/m2). The drug was supplied as 5 mg tablets alongside matching placebo so that participants in both groups received the same number of tablets at any time point in the study. A minimisation algorithm ensured balanced treatment allocation by ethnicity (South Asian, white, or other) and age (5 years or less, 6 years or more). MAIN OUTCOME MEASURES: The primary outcome measure was time to first relapse over a minimum follow-up of 24 months. Secondary outcome measures were relapse rate, incidence of frequently relapsing nephrotic syndrome and steroid dependent nephrotic syndrome, use of alternative immunosuppressive treatment, rates of adverse events, behavioural change using the Achenbach child behaviour checklist, quality adjusted life years, and cost effectiveness from a healthcare perspective. Analysis was by intention to treat. RESULTS: No significant difference was found in time to first relapse (hazard ratio 0.87, 95% confidence interval 0.65 to 1.17, log rank P=0.28) or in the incidence of frequently relapsing nephrotic syndrome (extended course 60/114 (53%) v standard course 55/109 (50%), P=0.75), steroid dependent nephrotic syndrome (48/114 (42%) v 48/109 (44%), P=0.77), or requirement for alternative immunosuppressive treatment (62/114 (54%) v 61/109 (56%), P=0.81). Total prednisolone dose after completion of the trial drug was 6674 mg for the extended course versus 5475 mg for the standard course (P=0.07). There were no statistically significant differences in serious adverse event rates (extended course 19/114 (17%) v standard course 27/109 (25%), P=0.13) or adverse event rates, with the exception of behaviour, which was poorer in the standard course group. Scores on the Achenbach child behaviour checklist did not, however, differ. Extended course treatment was associated with a mean increase in generic quality of life (0.0162 additional quality adjusted life years, 95% confidence interval -0.005 to 0.037) and cost savings (difference -£1673 ($2160; €1930), 95% confidence interval -£3455 to £109). CONCLUSIONS: Clinical outcomes did not improve when the initial course of prednisolone treatment was extended from eight to 16 weeks in UK children with steroid sensitive nephrotic syndrome. However, evidence was found of a short term health economic benefit through reduced resource use and increased quality of life. TRIAL REGISTRATION: ISRCTN16645249; EudraCT 2010-022489-29.


Assuntos
Assistência de Longa Duração , Síndrome Nefrótica , Prednisolona , Qualidade de Vida , Prevenção Secundária , Adolescente , Criança , Pré-Escolar , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Monitoramento de Medicamentos/métodos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/economia , Humanos , Imunossupressores/uso terapêutico , Lactente , Análise de Intenção de Tratamento , Assistência de Longa Duração/economia , Assistência de Longa Duração/métodos , Masculino , Síndrome Nefrótica/diagnóstico , Síndrome Nefrótica/tratamento farmacológico , Síndrome Nefrótica/economia , Síndrome Nefrótica/psicologia , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisolona/economia , Prevenção Secundária/economia , Prevenção Secundária/métodos , Resultado do Tratamento
9.
BMC Public Health ; 19(1): 788, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221143

RESUMO

BACKGROUND: Depression is the leading cause of disability in young people (aged 15-25) globally. Loneliness is a major factor in the development and relapse of depression in young people, yet few interventions directly address loneliness. Groups 4 Health (G4H) - a novel, theoretically derived group psychotherapy intervention - may address this disconnect. Previous trials (Phase I and Phase II) have found G4H to be efficacious in reducing symptoms of depression. However, the efficacy of G4H compared to current evidence-based treatments (Phase III) has not been investigated. This protocol details the design and methodology of the Connecting Adolescents to Reduce Relapse (CARR) trial, a randomised control trial assessing the efficacy of G4H in young people relative to cognitive behavioural therapy (CBT). METHODS: The CARR trial is a two-arm non-inferiority randomised controlled trial that will compare the efficacy of G4H to the most widely used evidence-based treatment for depression, CBT, at program completion and 6- and 12-month follow up. Participants will be 200 young people (aged 15-25) with symptoms of depression and/or loneliness recruited from community and university mental health services. We hypothesise that the interventions will be comparable in reducing depression symptoms, but that G4H will be superior in reducing loneliness. Because loneliness is a primary risk factor for depression relapse in young people, we therefore expect the benefits of Groups 4 Health to be particularly apparent at 12-month follow up. DISCUSSION: This trial will be the first to evaluate an intervention that targets loneliness, in comparison to the current gold standard treatment approach - CBT. If found to be effective, this program offers a new approach to treatment and relapse prevention of depression among young people. TRIAL REGISTRATION: Trial prospectively registered on ANZCTR ( ACTRN12618000440224 ), registered on 27/03/2018.


Assuntos
Terapia Cognitivo-Comportamental , Depressão/prevenção & controle , Psicoterapia de Grupo , Psicoterapia/métodos , Prevenção Secundária/métodos , Adolescente , Adulto , Depressão/psicologia , Humanos , Solidão/psicologia , Projetos de Pesquisa , Resultado do Tratamento , Adulto Jovem
10.
Mol Biol (Mosk) ; 53(3): 456-466, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31184611

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative therapy for hematopoietic malignancies. The graft-derived donor lymphocytes are capable of eliminating the residual recipient malignant cells in the course of allogeneic immune response, thus decreasing the chances of a relapse of the disease. Foreign peptides of the recipient presented by the MHC molecules are able to elicit the immune response immunologically. These polymorphic peptides are known as minor histocompatibility antigens (MiHAs). MiHAs occur due to the nonsynonymous single nucleotide polymorphisms in human genome. Transfusion of T cells specific to MiHAs presented predominantly in the cells of hematopoietic origin will allow the targeted elimination of residual malignant clones avoiding undesirable damage to healthy tissues. To induce the immune response, the donor must be homozygous by the MiHA allele and the recipient must either be homozygous or heterozygous by the alternative MiHA allele. The therapeutic mismatch occurs in 25% of cases under the optimal frequency of allelic variants. Minor antigen ACC-1Y originates from polymorphism in the BCL-2A1 gene; its immunogenic mismatch occurrence approaches the theoretical maximum. In addition, BCL2A1 is overexpressed in cells of various lymphomas. ACC-1Y is presented on allele HLA-A*24:02, which is relatively frequent in the Russian population. Combination of these factors makes the minor antigen ACC-1Y a promising target for immunotherapy. Transfusion of donor CD8^(+) lymphocytes modified with transgenic MiHA-specific TCR is one of the promising methods of posttransplant leukemia therapy and relapse prophylaxis. We obtained a sequence of high-affinity ACC-1Y-specific TCR after the antigen-specific expansion of T cells derived from a healthy ACC-IY^(-/-) donor. We cloned this sequence into the lentiviral vector and obtained the assembled viral particles. Further, we transduced the CD8^(+) lymphocyte culture and demonstrated its antigen-specific cytotoxic activity. It is suggested that CD8^(+) lymphocytes modified by the described method could be potentially transferred to recipients as a therapy against relapse after allo-HSCT.


Assuntos
Engenharia Celular , Transplante de Células-Tronco Hematopoéticas , Antígenos de Histocompatibilidade Menor/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Aloenxertos , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Humanos , Antígenos de Histocompatibilidade Menor/genética , Receptores de Antígenos de Linfócitos T/genética , Federação Russa , Prevenção Secundária/métodos
11.
BMC Health Serv Res ; 19(1): 364, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182100

RESUMO

BACKGROUND: Electronic health (e-Health) interventions are emerging as an effective alternative model for improving secondary prevention of coronary artery disease (CAD). The aim of this study was to describe the effectiveness of different modes of delivery and components in e-Health secondary prevention programmes on adherence to treatment, modifiable CAD risk factors and psychosocial outcomes for patients with CAD. METHOD: A systematic review was carried out based on articles found in MEDLINE, CINAHL, and Embase. Studies evaluating secondary prevention e-Health programmes provided through mobile-Health (m-Health), web-based technology or a combination of m-Health and web-based technology were eligible. The main outcomes measured were adherence to treatment, modifiable CAD risk factors and psychosocial outcomes. The quality appraisal of the studies included was conducted using the Joanna Briggs Institute critical appraisal tool for RCT. The results were synthesised narratively. RESULT: A total of 4834 titles were identified and 1350 were screened for eligibility. After reviewing 123 articles in full, 24 RCTs including 3654 participants with CAD were included. Eight studies delivered secondary prevention programmes through m-Health, nine through web-based technology, and seven studies used a combination of m-Health and web-based technology. The majority of studies employed two or three secondary prevention components, of which health education was employed in 21 studies. The m-Health programmes reported positive effects on adherence to medication. Most studies evaluating web-based technology programmes alone or in combination with m-Health also utilised traditional CR, and reported improved modifiable CAD risk factors. The quality appraisal showed a moderate methodological quality of the studies. CONCLUSION: Evidence exists that supports the use of e-Health interventions for improving secondary prevention of CAD. However, a comparison across studies highlighted a wide variability of components and outcomes within the different modes of delivery. High quality trials are needed to define the most efficient mode of delivery and components capable of addressing a favourable outcome for patients. TRIAL REGISTRATION: Not applicable.


Assuntos
Doença da Artéria Coronariana/terapia , Prevenção Secundária/métodos , Telemedicina , Reabilitação Cardíaca , Doença da Artéria Coronariana/reabilitação , Promoção da Saúde , Humanos , Estudos Prospectivos , Telemedicina/métodos
12.
Dis Colon Rectum ; 62(7): 882-892, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31188190

RESUMO

BACKGROUND: Despite significant advances in the medical management of Crohn's disease, many patients will require intestinal resection during their lifetime. It is disappointing that many will also develop disease recurrence. OBJECTIVES: The current study utilizes meta-analytical techniques to determine the effect of positive histological margins at the time of index resection on disease recurrence. DATA SOURCES: Embase, Medline, PubMed, PubMed Central, and Cochrane databases were searched using a Boolean search algorithm for articles published up to August 2017. STUDY SELECTION: Meta-analysis was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. MAIN OUTCOME MEASURES: Databases were searched for studies reporting the outcomes for patients with Crohn's disease undergoing primary resection that correlated resection margin status with disease recurrence. Results were reported as pooled ORs with 95% CI. RESULTS: A total of 176 citations were reviewed; 18 studies comprising 1833 patients were ultimately included in the analysis, with a mean rate of histopathological margin positivity of 41.7 ± 17.4% and a pooled mean follow-up of 69 ± 39 months. Histopathological margin positivity was associated with a higher rate of overall recurrence (OR, 1.7; 95% CI, 1.3-2.1; p < 0.001), clinical recurrence (OR, 1.7; 95% CI, 1.0-2.8; p = 0.04), and anastomotic recurrence (OR, 1.6; 95% CI, 1.0-2.3; p = 0.03). In studies reporting plexitis specifically at the resection margin, there was an increase in recurrence (OR, 2.3; 95% CI, 1.1-4.9; p = 0.02). LIMITATIONS: The definitions of histological margin positivity and postoperative recurrence vary between the studies and follow-up durations vary. CONCLUSIONS: The presence of involved histological margins at the time of index resection in Crohn's disease is associated with recurrence, and plexitis shows promise as a marker of more aggressive disease. Further studies with homogeneity of histopathological and recurrence reporting are required.


Assuntos
Doença de Crohn/patologia , Doença de Crohn/cirurgia , Margens de Excisão , Anastomose Cirúrgica/efeitos adversos , Humanos , Recidiva , Reoperação , Prevenção Secundária/métodos
13.
J Stroke Cerebrovasc Dis ; 28(8): 2124-2131, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31147254

RESUMO

BACKGROUND: Orthostatic hypotension (OH) has been independently associated with increased risk of stroke and other cardiovascular events. We sought to investigate the relationship between OH at follow-up and recurrent stroke risk in SPS3 (Secondary Prevention of Small Subcortical Strokes) trial patient cohort. This is a retrospective cohort analysis. METHODS: We included all SPS3 trial participants with blood pressure measurements in both sitting and standing position per protocol at baseline, with at least 1 follow-up visit to establish the relationship between OH at follow-up and recurrent stroke risk (primary outcome). Secondary outcomes included major vascular events, myocardial infarction, all-cause mortality, and, ischemic and hemorrhagic stroke subtypes. Participants were classified as having OH at baseline and at each follow-up visit based on a systolic BP decline ≥20 mm Hg or a diastolic BP decline ≥10 mm Hg on position change from sitting to standing. We used Cox proportional hazards regression modeling to compare the risk of outcomes among those with and without OH. RESULTS: A total of 2275 patients were included with a mean follow up time 3.2 years (standard deviation = 1.6 years). 39% (881/2275) had OH at some point during their follow-up. Of these, 41% (366/881) had orthostatic symptoms accompanying the BP drop. In a fully adjusted model, those with OH had a 1.8 times higher risk of recurrent stroke than those without OH (95% confidence interval: 1.1-3.0). The risk of ischemic stroke, major vascular events, and all-cause mortality was similarly elevated among the OH group. CONCLUSION: OH was associated with increased recurrent stroke risk, vascular events, and all-cause death in this large cohort of lacunar stroke patients. Whether minimizing OH in the management of poststroke hypertension in patients with lacunar stroke reduces recurrent stroke risk deserves further study.


Assuntos
Pressão Sanguínea , Hipotensão Ortostática/complicações , Prevenção Secundária/métodos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Causas de Morte , Feminino , Humanos , Hipotensão Ortostática/mortalidade , Hipotensão Ortostática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
14.
J Stroke Cerebrovasc Dis ; 28(8): 2268-2272, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31160220

RESUMO

BACKGROUND AND PURPOSE: Early disability after stroke is common, though many patients improve. Stroke secondary prevention trials often prohibit the recruitment of nonambulatory patients, limiting their access to potential treatment options and impeding trial enrollment. We aimed to determine outcomes after early dependence around the time of transition from acute care to recovery. METHODS: Data were obtained from a composite of patients enrolled in acute stroke clinical trials within the Virtual International Stroke Trials Archive (VISTA-Acute). Early disability was defined by the modified Rankin Scale (mRS) of 4 or 5 between days 3-10 after onset, representing the time of discharge or transition to a rehabilitation-focused care setting. We developed multivariable models to identify factors associated with recovery to independent ambulatory function and recurrent stroke during the 90 days after stroke. RESULTS: 4965 patients were included, with 2905 (59%) having early disability. Patients with early dependence were older, more likely to be women, had higher baseline NIHSS scores, and had more atrial fibrillation and diabetes mellitus, compared with those who were initially ambulatory. Recovery to ambulatory function occurred in 58% with early mRS = 4, compared to only 16% with early mRS = 5. Of those with early mRS = 4, return to independent ambulatory status by 90 days was associated in multivariable analysis with age, diabetes, prior stroke, NIH motor and gaze subscores, and thrombolysis. Recurrent ischemic stroke through day 90 was reported in 126 of 2905 (4.3%) subjects with early dependence compared to 63 of 2060 (3.1%), which was not different after adjustment for age, sex, and risk factors (odds ratio 1.27; 95% confidence interval 0.92-1.73). CONCLUSIONS: Favorable outcomes are common among ischemic stroke patients previously enrolled in acute clinical trials despite early dependence (mRS = 4) after initial acute hospital care. Further, their risk of recurrent stroke is high in the short term. These patients likely benefit from aggressive poststroke care and should be actively recruited into secondary prevention trials.


Assuntos
Ensaios Clínicos como Assunto/métodos , Avaliação da Deficiência , Definição da Elegibilidade , Seleção de Pacientes , Prevenção Secundária/métodos , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Limitação da Mobilidade , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Recidiva , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
15.
JAMA ; 321(21): 2092-2100, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31162569

RESUMO

Importance: Whether exercise reduces subsequent falls in high-risk older adults who have already experienced a fall is unknown. Objective: To assess the effect of a home-based exercise program as a fall prevention strategy in older adults who were referred to a fall prevention clinic after an index fall. Design, Setting, and Participants: A 12-month, single-blind, randomized clinical trial conducted from April 22, 2009, to June 5, 2018, among adults aged at least 70 years who had a fall within the past 12 months and were recruited from a fall prevention clinic. Interventions: Participants were randomized to receive usual care plus a home-based strength and balance retraining exercise program delivered by a physical therapist (intervention group; n = 173) or usual care, consisting of fall prevention care provided by a geriatrician (usual care group; n = 172). Both were provided for 12 months. Main Outcomes and Measures: The primary outcome was self-reported number of falls over 12 months. Adverse event data were collected in the exercise group only and consisted of falls, injuries, or muscle soreness related to the exercise intervention. Results: Among 345 randomized patients (mean age, 81.6 [SD, 6.1] years; 67% women), 296 (86%) completed the trial. During a mean follow-up of 338 (SD, 81) days, a total of 236 falls occurred among 172 participants in the exercise group vs 366 falls among 172 participants in the usual care group. Estimated incidence rates of falls per person-year were 1.4 (95% CI, 0.1-2.0) vs 2.1 (95% CI, 0.1-3.2), respectively. The absolute difference in fall incidence was 0.74 (95% CI, 0.04-1.78; P = .006) falls per person-year and the incident rate ratio was 0.64 (95% CI, 0.46-0.90; P = .009). No adverse events related to the intervention were reported. Conclusions and Relevance: Among older adults receiving care at a fall prevention clinic after a fall, a home-based strength and balance retraining exercise program significantly reduced the rate of subsequent falls compared with usual care provided by a geriatrician. These findings support the use of this home-based exercise program for secondary fall prevention but require replication in other clinical settings. Trial Registration: ClinicalTrials.gov Identifiers: NCT01029171; NCT00323596.


Assuntos
Acidentes por Quedas/prevenção & controle , Terapia por Exercício , Acidentes por Quedas/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Vida Independente , Masculino , Equilíbrio Postural , Treinamento de Resistência , Prevenção Secundária/métodos , Método Simples-Cego
17.
Medicine (Baltimore) ; 98(22): e15681, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145281

RESUMO

BACKGROUND: Studies that used short message service (SMS) programs as an intervention to promote health care have shown beneficial results in the control of risk factors for ischemic heart disease in patients of high-income countries, but evidence is lacking in low or middle-income countries. AIMS: The purpose of this study is to evaluate whether the use of SMS increases risk factor control within 6 months after discharge by acute coronary syndrome (ACS) in a middle-income country. METHODS: It will be a 2-arm, parallel, double-blind, randomized clinical trial of 160 patients discharged after an ACS from a single center with 6 months of follow-up. The intervention group will receive 4 SMS per week offering advice, motivation and information about medication adherence, increase of regular physical activity, adoption of healthy dietary measures, and smoking cessation (if appropriate). The primary outcome is achieving 4 or 5 points in a risk factor control score, which combines the cluster effect of 5 main modifiable risk factors for ACS [low-density lipoprotein cholesterol, LDL-C <70 mg/dL, blood pressure <140/90 mm Hg, regular exercise (≥5 days/week × 30 minutes of moderate exercise per session), nonsmoker status, and body mass index, BMI <25 kg/m]. Secondary outcomes are plasma LDL-C level, level of physical activity, blood pressure, medication adherence, proportion of nonsmokers, BMI, rehospitalization, cardiovascular death, and death from any cause. This study, as a randomized clinical trial protocol, followed the recommendations of the Standard Protocol Items (SPIRIT). EXPECTED OUTCOMES: This study aims to provide evidence of whether SMS interventions are effective in improving cardiovascular disease risk factors control in post-ACS patients in a middle-income country. CLINICALTRIALS. GOV IDENTIFIER: NCT03414190 (First posted on January 29, 2018; last update on May 14, 2018) - Retrospectively registered.


Assuntos
Síndrome Coronariana Aguda/terapia , Avaliação de Resultados (Cuidados de Saúde)/métodos , Prevenção Secundária/métodos , Telemedicina/métodos , Mensagem de Texto , Síndrome Coronariana Aguda/sangue , Pressão Sanguínea , LDL-Colesterol/sangue , Método Duplo-Cego , Exercício , Terapia por Exercício , Feminino , Humanos , Renda , Masculino , Adesão à Medicação , Motivação , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
18.
Medicine (Baltimore) ; 98(22): e15927, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31145359

RESUMO

INTRODUCTION: A network meta-analysis was conducted to regard the effects of available immunosuppressive medications in pediatric frequently-relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). METHODS: We reviewed systematically 26 randomized controlled trials (1311 patients) that compared any of the following immunosuppressive agents to placebo/nontreatment (P/NT) or another drug for FRNS/SDNS treatment in children. RESULTS: The main outcomes were efficacy and acceptability. At the 6-month, cyclophosphamide, chlorambucil, levamisole, and rituximab had better efficacy than P/NT (odds ratio [OR]: 0.09, 0.03, 0.28, and 0.07, respectively); cyclophosphamide was significantly more effective than azathioprine and chlorambucil. At 12 months, cyclophosphamide, chlorambucil, cyclosporine, levamisole, and rituximab had better efficacy than P/NT (0.10, 0.03, 0.10, 0.23, and 0.07, respectively); Chlorambucil were found to be more efficacious than levamisole and MMF (0.12 and 0.09, respectively). At 24 months, cyclophosphamide, chlorambucil, and levamisole had better efficacy than P/NT (0.09, 0.04, and 0.03, respectively); cyclophosphamide had better efficacy than cyclosporine and vincristine (0.17 and 0.39, respectively). CONCLUSION: No significant differences in acceptability were found. Our results suggest that cyclophosphamide may be preferred initially in children with FRSN/SDNS, chlorambucil, and rituximab may be acceptable medications for patients with FRSN/SDNS. Long-term follow-up trials focused on gonadal toxicity and limitation of maximum dosage of cyclophosphamide should been carried out.


Assuntos
Glucocorticoides/uso terapêutico , Imunossupressores/uso terapêutico , Síndrome Nefrótica/tratamento farmacológico , Adolescente , Azatioprina/uso terapêutico , Criança , Pré-Escolar , Clorambucila/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Lactente , Levamisol/uso terapêutico , Masculino , Meta-Análise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Rituximab/uso terapêutico , Prevenção Secundária/métodos , Resultado do Tratamento
19.
J Stroke Cerebrovasc Dis ; 28(7): 1860-1865, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31064695

RESUMO

BACKGROUND AND PURPOSE: Previous studies have shown that common variants within CYP3A4 and CYP3A5 are associated with statin pharmacokinetics and the risk of cardiovascular disease. However, the association of variants in CYP3A4 and CYP3A5 with the prognosis of ischemic stroke remains undetermined. Therefore, we investigated this herein. METHODS: Four hundred thirty-three consecutive patients with acute ischemic stroke were recruited. The outcome at the 1-year follow-up was assessed using the modified Rankin Scale (mRS). Two variants, CYP3A4*1G and CYP3A5*3, were genotyped by the improved Multiple Ligase Detection Reaction platform. RESULTS: Binary logistic regression analysis showed that the CYP3A4*1G/*1G homozygote was associated with poor outcome at 1 year (mRS score ≥2) after adjustment for conventional factors in the additive model (odds ratio [OR] = 2.92; 95% confidence interval, 1.07-7.98; P = .037) and recessive model (OR = 3.37; 95% confidence interval, 1.26-9.04; P = .016). Subgroup analysis indicated that the CYP3A4*1G/*1G homozygote was associated with poor prognosis at 1 year among patients with stable high-intensity atorvastatin therapy (40-80 mg/d) after adjustment for conventional factors in the additive model (OR = 8.16; 95% confidence interval, 1.50-44.44; P = .015) and recessive model (OR = 9.06; 95% confidence interval, 1.72-47.64; P = .009). No significant association was identified between CYP3A5*3 and the 1-year outcome of patients with ischemic stroke. CONCLUSIONS: Our study findings suggest that the CYP3A4*1G/CYP3A4*1G genotype may be associated with poor prognosis at 1 year after acute ischemic stroke in the Han Chinese population.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Isquemia Encefálica/genética , Citocromo P-450 CYP3A/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Acidente Vascular Cerebral/genética , Idoso , Atorvastatina/administração & dosagem , Atorvastatina/farmacocinética , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/enzimologia , Isquemia Encefálica/etnologia , China/epidemiologia , Citocromo P-450 CYP3A/metabolismo , Avaliação da Deficiência , Feminino , Frequência do Gene , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Prevenção Secundária/métodos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/enzimologia , Acidente Vascular Cerebral/etnologia , Fatores de Tempo , Resultado do Tratamento
20.
J Stroke Cerebrovasc Dis ; 28(7): 1810-1815, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31097326

RESUMO

OBJECTIVE: The concept of embolic stroke of undetermined source refers to cryptogenic strokes caused by either major or minor risks. Although antiplatelet treatments are most often used for secondary prevention of embolic stroke of undetermined source, optimal strategies remain unclear. To determine the ideal treatment strategy for secondary prevention, we investigated embolic sources among patients with embolic stroke of undetermined source. METHODS: The study included 292 consecutive patients (135 men, 157 women; mean age: 74.3 ± 11.6 years) diagnosed with cerebral infarction, 27 of whom were diagnosed with embolic stroke of undetermined source (9.2%; 14 men, 13 women; mean age: 70.7 ± 11.5 years). These 27 patients were examined using contrast-enhanced whole-body computed tomography, transesophageal echocardiography, and Holter electrocardiography. We evaluated whether antiplatelet or anticoagulant treatment was preferred based on the embolic source. RESULTS: Embolic sources among patients with embolic stroke of undetermined source included valve calcification (11.1%), left ventricle diastolic dysfunction (18.5%), cancer-associated stroke (25.9%), covert atrial fibrillation (7.4%), aortic arch atherosclerotic plaques (11.1%), paradoxical embolism (3.7%), and sick sinus syndrome (3.7%). Embolic sources remained unidentified in 5 patients (18.5%). Our analysis revealed that 21 of the 27 patients (77.8%) with embolic stroke of undetermined source required anticoagulant therapy for secondary prevention. CONCLUSION: Although aspirin is the most commonly used antithrombotic drug for embolic stroke of undetermined source, our results suggest that some patients require anticoagulant therapy. Determining embolic sources is important for selecting the appropriate treatment options for this patient population.


Assuntos
Embolia Intracraniana/etiologia , Acidente Vascular Cerebral/etiologia , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Imagem de Difusão por Ressonância Magnética , Ecocardiografia Transesofagiana , Eletrocardiografia Ambulatorial , Feminino , Humanos , Embolia Intracraniana/diagnóstico por imagem , Embolia Intracraniana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação de Plaquetas/uso terapêutico , Valor Preditivo dos Testes , Recidiva , Fatores de Risco , Prevenção Secundária/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/prevenção & controle , Tomografia Computadorizada por Raios X , Imagem Corporal Total/métodos
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