RESUMO
For the detection of unwanted outcomes of new interventions, physicians rely on adverse event reporting. We attempt to quantify the reported incidence of venous thromboembolism (VTE) and arterial thrombosis (AT) in randomized clinical trials (RCTs), and evaluate the extent of under-reporting. We selected all therapeutic RCTs published in the four highest-impact general medicine journals between January 2011 and July 2011. Patients were categorized according to VTE risk. The occurrences of VTE and AT, either as predefined outcome or adverse event, were assessed. We identified 131 RCTs. VTE and AT were not reported in 89 and 70 % of these studies, respectively. The raw-unweighted reported incidence in the 3 studies with predefined outcomes for VTE was 8.4 (7.8-9.1) per 1,000 person-years. In the 128 studies without predefined outcomes for VTE, (consisting of 322,029 individuals, including patients with cancer, inflammatory disease, cardiovascular disease, surgery, adding up to a follow-up >500,000 person-years), an incidence of 0.4 (0.4-0.5) per 1,000 person-years was found. The reported incidence of AT in 18 studies in which AT was part of predefined outcomes was 25.6 (24.9-26.3) per 1,000 person-years. In 92 studies without predefined outcomes for AT (231,638 individuals, follow-up >200,000 person-years,), the incidence was 2.5 (2.3-2.7) per 1,000 person-years. The incidence of VTE and AT in RCTs is highly under-reported. Uniform registration of adverse events, even when unlikely to be related to the intervention, is necessary to be able to inform physicians about the potential toxicities of new therapeutic strategies.
Assuntos
Artérias/patologia , Embolia/epidemiologia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Projetos de Pesquisa/normas , Tromboembolia Venosa/epidemiologia , Humanos , Incidência , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Fatores de RiscoRESUMO
Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of thyroid diseases, cortisol excess and deficiency, pheochromocytoma, hyperparathyroidism, hyperaldosteronism, hyperprolactinemia, and growth hormone excess and deficiency; on parameters of hemostasis; and on arterial and venous thrombotic events. All these endocrine diseases do have, or may have, influence either on hemostasis or on the risk of thrombotic events. Future studies are needed to establish the clinical relevance of these associations.
Assuntos
Arteriopatias Oclusivas/complicações , Doenças do Sistema Endócrino/complicações , Hemostasia , Trombose/complicações , Trombose Venosa/complicações , Hormônio do Crescimento/deficiência , Hormônio do Crescimento/metabolismo , Humanos , Hidrocortisona/deficiência , Hidrocortisona/metabolismo , Doenças da Glândula Tireoide/complicaçõesRESUMO
BACKGROUND: Recently, endogenous glucocorticoid excess has been identified as a risk factor for VTE. Whether exogenous use of glucocorticoids is associated with an increased risk of VTE is unclear. We aimed to quantify the risk of symptomatic pulmonary embolism (PE) in patients using corticosteroids. METHODS: A case-control study using the PHARMO Record Linkage System, a Dutch population-based pharmacy registry, was conducted. Cases were 4,495 patients with a first hospital admission for PE between 1998 and 2008. Control subjects were 16,802 sex- and age-matched subjects without a history of PE. International Classification of Diseases codes for hospitalization were used to retrieve information on underlying conditions. RESULTS: The risk of PE was highest in the first 30 days of glucocorticoid exposure (adjusted OR, 5.9; 95% CI, 2.3-3.9) and gradually decreased with increasing duration of use (OR, 1.9; 95% CI, 1.3-2.9) for long-term users (> 1 year). Low-dose glucocorticoid use (prednisolone daily dose equivalent < 5 mg) carried a twofold increased risk of PE (OR, 1.8; 95% CI, 1.3-2.4), whereas a 10-fold increased risk was observed for the highest dose of glucocorticoids (prednisolone > 30 mg) (OR, 9.6; 95% CI, 4.3-20.5). Stratification for both duration and dose of glucocorticoid showed the highest risk of PE in recently started users compared with long-term users at the time of PE, irrespective of the dose. CONCLUSION: Patients treated with oral glucocorticoids may be at an increased risk of PE, especially during the first month of exposure. This hypothesis requires confirmation in future studies.
Assuntos
Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Embolia Pulmonar/epidemiologia , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite/tratamento farmacológico , Asma/tratamento farmacológico , Estudos de Casos e Controles , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/uso terapêutico , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Endocrine disorders affect both the coagulation and fibrinolytic systems, and have been associated with the development of cardiovascular diseases. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a link between coagulation and the fibrinolytic system. The aim of this study was to determine the effect of thyroid hormone excess and deficiency on TAFI levels and function. The effect of hyperthyroxinemia on TAFI was studied in healthy volunteers who were randomised to receive levothyroxine or no medication for 14 days in a crossover design. The effect of hypothyroidism on TAFI was studied in a multicentre observational cohort study. Blood was drawn before treatment of patients with newly diagnosed hypothyroidism and when euthyroidism was achieved. Plasma clot-lysis times, activated TAFI (TAFIa)-dependent prolongation of clot-lysis and TAFI levels were measured. Thyroid hormone excess resulted in a hypofibrinolytic condition and in an enhanced TAFIa-dependent prolongation of clot lysis. A trend towards decreased plasma TAFI levels was observed in healthy volunteers who used levothyroxine. Hypothyroidism resulted in hyperfibrinolysis and a reduced TAFIa-dependent prolongation of clot lysis. In conclusion, alterations of TAFIa-dependent prolongation of clot lysis in patients with thyroid disorders may cause an impaired haemostatic balance. The disturbed haemostatic balance in patients with hyperthyroidism might make them prone to thrombosis, while the risk for bleeding may increase in patients with hypothyroidism.
Assuntos
Carboxipeptidase B2/sangue , Hemostasia , Hipertireoxinemia/sangue , Hipotireoidismo/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea , Estudos Cross-Over , Feminino , Tempo de Lise do Coágulo de Fibrina , Fibrinólise , Hemorragia/sangue , Hemorragia/etiologia , Hemostasia/efeitos dos fármacos , Humanos , Hipertireoxinemia/complicações , Hipotireoidismo/complicações , Masculino , Pessoa de Meia-Idade , Países Baixos , Método Simples-Cego , Trombose/sangue , Trombose/etiologia , Tireotropina/sangue , Tiroxina/administração & dosagem , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Toxocara infection is associated with an increased prevalence of airway symptoms and may be a possible aetiologic agent of chronic cough. The occurrence of toxocariasis in Hungary is mild and/or sporadic. The purpose of this study was to investigate the levels of serum cytokines (IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IFN-gamma and TNF-alpha) and total IgE, the blood eosinophil count, the results of skin prick and non-specific bronchus provocation tests in Toxocara-seropositive children with chronic cough relative to those in healthy controls. The patients exhibited moderate eosinophilia, significantly elevated levels of serum total IgE, IL-6, IL-10, IL-13 and IFN-gamma, and higher skin reactivity to common allergens, whereas the bronchial hyperreactivity was similar in the two groups. The protective proinflammatory cytokines (IL-6, IFN-gamma and IL-13) in association with the anti-inflammatory cytokine (IL-10) were simultaneously increased in Toxocara-infected children with chronic cough. During infections, the activation and suppression of immune processes occur simultaneously and cytokines of Th1/Th2 and regulatory T cells contribute to the regulation of the immune response evoked by helminth infections (depending on the parasite load, the timing and duration of the infection and the status of the host immune system).
Assuntos
Tosse/etiologia , Citocinas/sangue , Toxocara canis/imunologia , Toxocara canis/patogenicidade , Toxocaríase/imunologia , Toxocaríase/patologia , Adolescente , Animais , Criança , Pré-Escolar , Eosinófilos , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Contagem de Leucócitos , MasculinoRESUMO
Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.
Assuntos
Hipertireoidismo/sangue , Coagulação Sanguínea/fisiologia , Fatores de Coagulação Sanguínea/metabolismo , Fibrinólise/fisiologia , Humanos , Hipertireoidismo/complicações , Fatores de Risco , Trombose/sangue , Trombose/etiologia , Tireotoxicose/sangueRESUMO
The pituitary hormone prolactin is thought to influence coagulation. We aimed to study the relation between prolactin levels, coagulation factors and risk of venous thrombosis (VT). We used data from a large population based case-control study into aetiology of first VT (MEGA-study). Prolactin levels were determined in 2,068 patients with VT and 2,785 age- and sex matched control subjects. The relation between levels of coagulation factors and prolactin was studied among the controls. In addition, odds ratios (OR) and 95% confidence intervals (95%CI) were calculated for the risk of VT for different cut-off points of prolactin levels based on percentiles determined in the controls. Restricted analysis was performed among cases in whom blood was sampled within six months after VT. We found a rise in factor VIII and von Willebrand factor with increasing levels of prolactin in the controls. An increased risk of VT was observed when blood was sampled within six months after thrombosis (OR 2.9, 95%CI 1.1-8.1) for prolactin levels above the 99th percentile (42.6 µg/l) relative to levels between the 20th to 80th percentile. When blood was sampled more than six months after VT no clear association could be observed (OR 1.3, 95%CI 0.7-2.3). In conclusion, we found a modest association between prolactin and symptomatic venous thromboembolism, particularly when blood was sampled close to the event. This may be explained by a causal relation or by prolactin being a marker of stress due to the thrombotic event.
Assuntos
Fator VIII/análise , Prolactina/sangue , Tromboembolia Venosa/epidemiologia , Fator de von Willebrand/análise , Adulto , Idoso , Proteína C-Reativa/análise , Estudos de Casos e Controles , Anticoncepcionais Orais Hormonais/efeitos adversos , Convalescença , Feminino , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hiperprolactinemia/sangue , Hiperprolactinemia/epidemiologia , Masculino , Menopausa/sangue , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Gravidez , Complicações Hematológicas na Gravidez/sangue , Complicações Hematológicas na Gravidez/epidemiologia , Recidiva , Risco , Fatores de Risco , Fatores de Tempo , Tromboembolia Venosa/sangue , Adulto JovemRESUMO
Hyperthyroidism is associated with several changes in the haemostatic system resulting in a hypercoagulable state. It is uncertain at this stage whether this leads to an increased risk of venous thromboembolism (VTE). The aim of this retrospective cohort study was to determine the risk of VTE in all patients with overt hyperthyroidism and to compare this to the risk of VTE in the general population. In three hospitals in the Netherlands, patients with biochemically confirmed hyperthyroidism caused by Graves' disease, multinodular goiter or toxic adenoma were included. All available electronic and handwritten records were examined. Primary outcome was the occurrence of VTE within six months before and until six months after the diagnosis of hyperthyroidism. We included a total of 587 patients. Five patients experienced a VTE during the study period, resulting in an incidence rate of 8.7 (95% CI 2.8 - 20.2) per 1,000 person-years. Three of these five patients had a first VTE (incidence rate for first VTE was 5.3 [95% CI 1.1 - 15.6] per 1,000 person-years). Incidence rates of VTE in the general population are between 0.6 and 1.6 per 1,000 person-years for first VTE and 0.7 and 1.8 per 1,000 person-years for all VTE. In conclusion, the incidence rate of VTE in patients with hyperthyroidism appears to be high. Future prospective studies are needed to further explore this possible association and to address its clinical implications.
Assuntos
Doença de Graves/epidemiologia , Hipertireoidismo/epidemiologia , Tromboembolia Venosa/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Doença de Graves/sangue , Doença de Graves/complicações , Humanos , Hipertireoidismo/sangue , Hipertireoidismo/complicações , Incidência , Masculino , Pessoa de Meia-Idade , Países Baixos , Estudos Retrospectivos , Risco , Tromboembolia Venosa/sangue , Tromboembolia Venosa/etiologia , Adulto JovemRESUMO
We describe 2 patients, a 49-year-old man presenting with dyspnoea and fatigue, and a 50-year-old woman referred for hypercholesterolaemia and hypertension. Both patients appeared to have hypothyroidism-induced dyslipidaemia. The lipid abnormalities resolved completely following thyroid hormone replacement therapy. Hypothyroidism is a well-known cause of secondary dyslipidaemia and may therefore predispose to the development of atherosclerotic disease. Measurement of thyroid hormone levels are, however, often not included in the screening of dyslipidaemia patients. The cases presented illustrate the insidious and diverse clinical presentations and diagnostic challenges of hypothyroidism. In addition, these cases demonstrate that clinical and biochemical screening for thyroid dysfunction is of paramount importance in all dyslipidaemia patients to prevent inappropriate initiation of lipid-lowering therapy.
Assuntos
Dislipidemias/etiologia , Hipotireoidismo/complicações , Hormônios Tireóideos/uso terapêutico , Diagnóstico Diferencial , Erros de Diagnóstico , Dislipidemias/diagnóstico , Dislipidemias/tratamento farmacológico , Feminino , Humanos , Hipolipemiantes/uso terapêutico , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Atherothrombosis is a multifactorial process, governed by an interaction between the vessel wall, hemodynamic factors and systemic atherothrombotic risk factors. Recent in vitro, human ex vivo and animal studies have implicated the hormone prolactin as an atherothrombotic mediator. To address this issue, we evaluated the anatomy and function of various microvascular beds as well as plasma atherothrombosis markers in patients with elevated prolactin levels. In this pilot study, involving 10 prolactinoma patients and 10 control subjects, sidestream dark field (SDF) imaging revealed a marked perturbation of the sublingual microcirculation in prolactinoma patients compared to control subjects, as attested to by significant changes in microvascular flow index (2.74 ± 0.12 vs. 2.91 ± 0.05, respectively; P = 0.0006), in heterogeneity index (0.28 [IQR 0.18-0.31] vs. 0.09 [IQR 0.08-0.17], respectively; P = 0.002) and lower proportion of perfused vessels (90 ± 4.0% vs. 95 ± 3.0%, respectively; P = 0.016). In the retina, fluorescein angiography (FAG) confirmed these data, since prolactinoma patients more often have dilatated perifoveal capillaries. In plasma, prolactinoma patients displayed several pro-atherogenic disturbances, including a higher endogenous thrombin potential and prothrombin levels as well as decreased HDL-cholesterol levels. Prolactinoma patients are characterized by microvascular dysfunction as well as plasma markers indicating a pro-atherothrombotic state. Further studies are required to assess if prolactin is causally involved in atherothrombotic disease.
Assuntos
Microcirculação/fisiologia , Prolactinoma/sangue , Prolactinoma/fisiopatologia , Adulto , HDL-Colesterol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prolactinoma/metabolismo , Protrombina/metabolismo , Trombina/metabolismoAssuntos
Anticoagulantes/uso terapêutico , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/epidemiologia , Trombose/tratamento farmacológico , Trombose/epidemiologia , Vitamina K/antagonistas & inibidores , Idoso , Comorbidade , Feminino , Humanos , Masculino , Países Baixos/epidemiologia , Prevalência , Medição de Risco , Fatores de Risco , Resultado do TratamentoRESUMO
Human trichinellosis was first documented in Hungary in 1891 and then there were an increased number of reports up to 1964 when the most severe outbreak occurred. After that, no information was available on the international literature on human trichinellosis which occurred from 1965 up to the present years. The aim of this study was to collect all the data available in Hungarian official data-sources on human trichinellosis which occurred from 1965 up to 2009 in Hungary. Furthermore, a comparative analysis was performed on the different serological tests used along the 45 years of investigation. In the period in question, 573 infections were documented in Hungary. Of them, 57 occurred in the years 1965-69, 130 in 1970-79, 302 in 1980-89, 27 in 1990-99, and 57 in 200009. The most common sources of infection were pork from backyard pigs and hunted wild boars. Sporadic cases and small family outbreaks marked the last ten years. The comparison of serological tests shows that the ELISA is a good test for the first screening, but ELISA-positive serum samples should be confirmed by western blot except for clinically clear-cut cases.
Assuntos
Triquinelose/epidemiologia , Animais , Surtos de Doenças/estatística & dados numéricos , Documentação/métodos , Ensaio de Imunoadsorção Enzimática , Humanos , Hungria/epidemiologia , Política , Prevalência , Suínos/parasitologia , Trichinella/isolamento & purificação , Triquinelose/transmissãoRESUMO
Chronic cough lasting 8 weeks or more often seems to be an intractable problem in childhood. Toxocara infection is associated with an increased prevalence of airway symptoms and may be the possible aetiological agent of chronic cough. Of 425 children aged 2-17 years with chronic cough who were investigated for toxocariasis and the distribution of bronchial asthma (BA), cough variant asthma (CVA) and non-asthmatic eosinophilic bronchitis (NAEB), 136 (32%) were seropositive for Toxocara canis antigens. Ninety-three of the 136 were adequately assessed, diagnosed and followed up during 1 year. BA was diagnosed in 40%, CVA in 27% and NAEB in 33% of the children. The eosinophil cell count, serum T. canis IgG levels and symptoms are predictors of the improvement or the decline of the condition. Presuming the aetiopathogenetic role of T. canis in the inflammatory process of chronic cough, we treated the children not only with inhaled corticosteroid (ICS), but also with a 1-week course of anthelminthics. We could significantly decrease the dose of ICS in 23 (62%) of the 37 with BA. The administration of anthelminthics and the avoidance of sensitizers were sufficient for those with NAEB; none needed ICS. ICS therapy could be stopped 2-3 months later in 17 (68%) of the 25 with CVA. We found that 8 of the 25 with CVA (32%) presented asthmatic symptoms at the end of the 1-year period. In Hungary, T. canis may be a potential sensitizer for chronic cough in seropositive children. Deworming therapy will then alleviate the airway symptoms without exacerbation in patients with BA, and have a positive effect on those with NAEB and the majority of those with CVA.
Assuntos
Tosse/parasitologia , Toxocaríase/complicações , Adolescente , Alérgenos , Animais , Anti-Helmínticos/uso terapêutico , Anticorpos Anti-Helmínticos/sangue , Testes de Provocação Brônquica , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Doença Crônica , Tosse/tratamento farmacológico , Tosse/imunologia , Quimioterapia Combinada , Eosinofilia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Hungria , Imunoglobulina G/sangue , Testes Intradérmicos , Estudos Longitudinais , Masculino , Estudos Soroepidemiológicos , Espirometria , Toxocara canis/imunologia , Toxocaríase/tratamento farmacológico , Toxocaríase/imunologiaRESUMO
The disease process of uveitis due to Toxocara canis infection has a much more severe course in children than in adults. It can be cured by special drugs (Mintezol) and corticosteroids, which at the same time also reduce the inflammatory symptoms. In patients with endophthalmitis, vitrectomy may be indicated. The improvement in visual acuity depends both on the localization of the degenerations and on the duration of the disease. The authors consider sonographic examination indispensable for differential diagnosis.