RESUMO
Anticoagulant therapy reduces deaths and disability in patients with or at risk of both arterial and venous thromboembolism. Highly effective antithrombotic therapies now exist that reduce the risk of both arterial thrombosis and venous thrombosis. Anticoagulant strategies include platelet inhibition, using a variety of potent platelet inhibitors, and antithrombotic therapy, designed to interfere with thrombosis by blocking activation of the coagulation cascade. All anticoagulants increase the risk of bleeding. Older antithrombotic agents have, in most cases, effective antidotes and well-developed (although perhaps not very evidence-based) treatment strategies. Newer anticoagulants, and most antiplatelet drugs, do not have effective antidotes or well-tested reversal strategies. This narrative review will provide advice on the diagnosis and management of anticoagulant bleeding with a particular focus on the antithrombotic drugs, including warfarin, heparin, and the novel agents.
Assuntos
Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/diagnóstico , Anticoagulantes/administração & dosagem , Gerenciamento Clínico , Hemorragia/tratamento farmacológico , HumanosAssuntos
Antitrombinas/efeitos adversos , Benzimidazóis/efeitos adversos , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Protrombina/administração & dosagem , beta-Alanina/análogos & derivados , Idoso de 80 Anos ou mais , Encéfalo/patologia , Dabigatrana , Feminino , Hematoma Subdural/induzido quimicamente , Hematoma Subdural/diagnóstico , Hematoma Subdural/tratamento farmacológico , Hemorragia/diagnóstico , Humanos , Masculino , Tomografia Computadorizada por Raios X , beta-Alanina/efeitos adversosRESUMO
PURPOSE: The objective of this study is to estimate the proportion of the relationship between low socioeconomic status (SES) and the incidence of these cancer types accounted for by health risk behaviors. METHODS: A study population of 569 bladder, 592 colon, and 558 rectal cancer cases and 1549 controls was used to investigate health risk behaviors and SES effects. Odds ratios and 95 % confidence intervals (CIs) estimated by multivariate logistic regression approximated relative risks. The explanatory role of health risk behaviors was assessed by the change in the risk estimate on SES following their omission from the model. RESULTS: For each cancer site, individual education remained a predictor of risk after controlling for health risk behaviors. Adjustments for health risk behaviors (smoking) shifted the age- and sex-adjusted relative risk (RR) associated with bladder cancer from 2.24 to 1.74 (29.5%). No health risk behaviors (smoking, diet, obesity) resulted in substantial change in the low education risk estimates for colon cancer (RR = 2.88) or rectal cancer (RR = 2.42). CONCLUSIONS: Given the strength of SES relationships persisting after adjustment for health risk behaviors, this study suggests that our knowledge of SES pathways and risk factors for bladder, colon, and rectal cancers is incomplete.
Assuntos
Neoplasias Colorretais/etiologia , Comportamentos Relacionados com a Saúde , Classe Social , Neoplasias da Bexiga Urinária/etiologia , Adulto , Idoso , Neoplasias Colorretais/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Assunção de Riscos , Inquéritos e Questionários , Neoplasias da Bexiga Urinária/epidemiologiaRESUMO
While an association between low socio-economic status (SES) and increased risk of stillbirth has been observed consistently over several decades, the pathways through which SES exerts these effects have not been established. Given that some key health-risk behaviours for stillbirth, including smoking and pre-pregnancy obesity, have strong relationships with SES, health-risk behaviours may serve as a channel through which low SES contributes to stillbirth outcomes. The objective of this study was to estimate the proportion of the relationship between low SES and the occurrence of stillbirth that is explained by health-risk behaviours in populations of Eastern Ontario and Nova Scotia (112 stillbirth cases and 398 controls). Both area and individual level influences of SES were assessed. The study population consisted of 112 cases (women delivering stillborn infants) and 398 controls. Odds ratios and 95% confidence intervals estimated by multivariable logistic regression were used to approximate relative risks. The contribution of health-risk behaviours to relationships between SES and stillbirth was assessed by a change in the relative risk estimate following omission of each health-risk behaviour from the model. Of the three measures of individual level SES examined (household income, education, Blishen occupational index), only household income was a statistically significant predictor of stillbirth. After controlling for individual level SES, no community level SES effects were observed for stillbirth. Adjustments for key health-risk behaviours (smoking) resulted in an 18.5% reduction in the odds ratio estimate for low SES, from 3.31 to 2.79. This large unexplained SES effect that remained highlights the need for research into other potential pathways that may account for increased risk of stillbirth among those of lower SES.
Assuntos
Classe Social , Natimorto/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Exercício Físico , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Idade Materna , Análise Multivariada , Nova Escócia/epidemiologia , Ontário/epidemiologia , Gravidez , Fatores de Risco , Assunção de Riscos , Fumar/efeitos adversos , Fatores SocioeconômicosRESUMO
BACKGROUND: Chronic lymphocytic leukemia (CLL) patients with 11q22.3 deletion (11q-) have an aggressive clinical course, and thus selection of first-line therapy in this group is important. This study aimed to improve our understanding of real-world practice patterns and outcomes of CLL patients with 11q- in a population-based setting. PATIENTS AND METHODS: The British Columbia CLL Database was used to identify patients with 11q-. Overall survival (OS) and treatment-free survival (TFS) were assessed after adjustment for prognostic factors. RESULTS: Of 1044 patients in the database, 125 had 11q- (12%). Sixty-nine patients had 11q- identified before therapy initiation and had a median OS and TFS of 14.7 (95% confidence interval [CI], 11.3-18.1) and 2.5 (95% CI, 1.5-3.6) years. Patient with copresence of 11q- and deletion 17p had a markedly worse prognosis, with median OS of 4.9 versus 14.7 years (P < .001). Most treated patients (33 of 52) received fludarabine with or without rituximab (FR). Patients treated with FR had a median OS of 12.8 years (standard error, 1.0), which was not statistically different from those treated with alkylator-containing therapy (P = .35). CONCLUSION: Although median TFS of 11q- patients in this cohort was short at 2.5 years, OS remains long at 14.7 years, even when most patients received initial treatment without alkylators.
Assuntos
Cromossomos Humanos Par 11/genética , Hibridização in Situ Fluorescente/métodos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Colúmbia Britânica , Canadá , Estudos de Coortes , Citogenética , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Deleção de Sequência , Análise de SobrevidaRESUMO
BACKGROUND: Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review and a meta-analysis of randomised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response. METHODS: We searched MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Library Database for papers published from 1970 to July, 2016, and abstracts from American Society of Hematology annual meetings published from 2004 to 2015 for randomised trials comparing different corticosteroid regimens for patients with previously untreated immune thrombocytopenia who achieved a platelet count response. Trials that compared corticosteroids exclusively with other interventions were excluded. The primary endpoint was overall (platelets >30â×â109/L) and complete (platelets >100â×â109/L) platelet count response at 6 months with high-dose dexamethasone compared with standard-dose prednisone. Children and adults were analysed separately. Estimates of effect were pooled with a random-effects model. FINDINGS: Nine randomised trials (n=1138) were included. Of those, five (n=533) compared one to three cycles of dexamethasone (40 mg per day for 4 days) with prednisone (1 mg per kg) for 14-28 days followed by dose tapering in adults. We found no difference in overall platelet count response at 6 months (pooled proportions 54% vs 43%, relative risk [RR] 1·16, 95% CI 0·79-1·71; p=0·44). At 14 days, overall platelet count response was higher with dexamethasone (79% vs 59%, RR 1·22, 95% CI 1·00-1·49; p=0·048). The dexamethasone group had fewer reported toxicities. Long-term response rates were similar when the data were analysed by cumulative corticosteroid dose over the course of treatment. No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children. INTERPRETATION: In adults with previously untreated immune thrombocytopenia, high-dose dexamethasone did not improve durable platelet count responses compared with standard-dose prednisone. High-dose dexamethasone might be preferred over prednisone for patients with severe immune thrombocytopenia who require a rapid rise in platelet count. FUNDING: Canadian Institutes of Health Research, and Canadian Blood Services, and Health Canada.
Assuntos
Anti-Inflamatórios/administração & dosagem , Dexametasona/administração & dosagem , Prednisona/administração & dosagem , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Adulto , Idoso , Criança , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Metanálise como Assunto , Pessoa de Meia-Idade , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVE: Rofecoxib, a selective cyclo-oxygenase-2 (COX-2) inhibitor, has been associated with increased arterial thrombosis. It is unknown whether (COX-2) inhibition is associated with venous thromboembolism (VTE).We investigated, using a systematic review of the literature, the association between rofecoxib and venous thrombosis. METHODS: A search strategy was developed and implemented to identify all English language studies in which rofecoxib was compared with placebo, irrespective of the primary outcome of the study. Study methodology and results were reviewed in a standardized manner using RefMan software. Confidence intervals and risk difference were calculated using a Poisson distribution. RESULTS: The search strategy identified 1339 papers; 15 studies met our pre-specified inclusion criteria. The majority of trials were short in duration (~12 weeks). All studies met at least two of the three quality criteria. In 15,160 (9217 person years follow up) patients allocated to rofecoxib there were 8 VTEs reported, compared with 9 VTEs in 13147 (9092 person years) patients allocated to placebo (relative risk 0.87, 95% CI 0.29-2.56, p=NS). The estimated incidence of VTE was 86.8 per 100,000 (95% CI 37.5 -171.2) person years with rofecoxib, and 99.1 per 100,000 person years with placebo (95%CI 45.3 - 188). This difference is not statistically significant (p=0.78). CONCLUSIONS: Our findings are limited by the relatively small number of events, although, the contributing sample size of 28307 subjects (18309 person years) is reasonable. From our best available data outlined in this manuscript, there is no increase in the risk of VTE with rofecoxib use.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Inibidores de Ciclo-Oxigenase 2/efeitos adversos , Lactonas/efeitos adversos , Sulfonas/efeitos adversos , Tromboembolia Venosa/induzido quimicamente , Humanos , Fatores de RiscoRESUMO
OBJECTIVES/HYPOTHESIS: The objective of this study was to examine the evidence for an association between patient and/or provider-related diagnostic delay and late stage at diagnosis. STUDY DESIGN: We identified all English language published studies worldwide and present a summary of the direction and magnitudes of the associations observed. We consider the role of study population characteristics and symptom variation across the head and neck cancer sites on the delay-stage association. RESULTS: The 27 eligible studies reviewed varied considerably in the cancer types grouped by analysis, types of delay, and measurement of delay. The relationship between diagnostic delay and stage at diagnosis varied in direction and magnitude, with no consistent positive association in any of the head and neck cancer sites. CONCLUSIONS: Possible explanations for the lack of an observed relationship between patient delay and stage include: inaccurate measurement of delay, lack of sensitivity of disease stage to delay-related disease progression, and variation in tumor aggressiveness, which could lead to variation in symptom progression rates. We call for better evidence about the relationship between diagnostic delay and disease progression and/or disease outcomes. If demonstrated and validated, such associations would provide a much stronger argument than description of delay alone for education programs around symptom recognition and for more active screening of high-risk individuals.