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Essentials Competing risk by death may lead to overestimation of venous thromboembolism (VTE) risk in cancers. We assessed the risk of VTE in cancer with and without accounting for competing risk by death. The risk of VTE was influenced by the mortality rate and the time since cancer diagnosis. Competing risk by death should be taken into account when exploring VTE risk in cancer. SUMMARY: Background Venous thromboembolism (VTE) is a common complication in cancer, and studies have suggested that aggressive cancers create the highest risk of VTE. However, competing risk by death may result in overestimation of VTE risk in patients with cancers associated with high mortality. Therefore, we estimated the risk of VTE by cancer site, accounting for the differential mortality between cancers. Methods The Scandinavian Thrombosis and Cancer cohort included 144 952 participants followed from 1993-1997 to 2008-2012. Incidence rates, cause-specific hazard ratios (HRs) and subdistribution HRs (SHRs) were assessed for overall cancer and by cancer site according to time intervals since cancer diagnosis. Results During follow-up, 14 272 subjects developed cancer, and 567 had cancer-related VTE. In cause-specific analyses, the VTE risk was highest in the first 6 months after cancer diagnosis (HR 17.5, 95% confidence interval [CI] 15.1-20.3), and declined rapidly thereafter. However, when mortality was taken into account, the risk was similar in the periods 6 months before (SHR 4.8, 95% CI 3.6-6.4) and 6 months after (SHR 4.6, 95% CI 3.9-5.4) cancer diagnosis. The range of the 2-year cumulative VTE incidence rates was substantially narrowed for all cancer sites after competing risk by death was taken into account (from 1-10% to 1-4%). Conclusion VTE risk by cancer site was influenced by the mortality rate and the time since cancer diagnosis. Our findings suggest that the cancer itself is a major contributor to VTE risk, and that competing risk by death should be taken into account when VTE risk in cancer is explored.
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Neoplasias/diagnóstico , Neoplasias/mortalidad , Tromboembolia Venosa/mortalidad , Adulto , Anciano , Dinamarca/epidemiología , Femenino , Finlandia/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias/sangre , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Tromboembolia Venosa/sangre , Tromboembolia Venosa/diagnóstico , Adulto JovenRESUMEN
Essentials Impact of cancer stage on venous thromboembolism (VTE) risk is not well-known in all cancers. The Scandinavian Thrombosis and Cancer Cohort provides person-time data and validated VTEs. Impact of cancer stage on VTE incidence tended to vary with cancer type. Cancer stage may not per se be a risk factor for VTE in all cancer types. SUMMARY: Background Absolute measures of the impact of cancer stage on the incidence of venous thromboembolism (VTE) in patients with distinct cancer types have not been investigated in a large population-based cohort study. Objectives To investigate differences in the incidence rates of objectively confirmed VTE according to the development of cancer in a large population-based cohort study. Cancer type and stage at the time of diagnosis were taken into account. Patients and Methods The Scandinavian Thrombosis and Cancer Cohort includes data regarding cancer types, stages and objectively confirmed VTE diagnoses among 144 952 participants followed from 1993 to 2012. We studied stage-specific incidence rates of VTE, and calculated incidence rate differences (IRDs) for VTE according to stages in patients with 10 types of solid cancer. Results During the entire follow-up, 335 VTEs occurred, of which 293 occurred within 5 years. The IRD of VTE in patients with distant metastasis as compared with those with localized disease indicated large variation depending on cancer type. The highest IRD was observed for pancreatic cancer (IRD of 187.0 × 10-3 person-years [p-y]; 95% confidence interval [CI] - 6.7 to 380.8), and the lowest IRD was observed for prostate cancer (IRD of 3.7 × 10-3 p-y; 95% CI - 7 to 15.2). Regional spread as compared with localized disease also indicated large variation depending on cancer type; the highest IRD was observed for uterine cancer (IRD of 37.6 × 10-3 p-y; 95% CI - 23.7 to 99), and the IRDs for breast and prostate cancer were close to zero. Conclusion More advanced cancer at the time of diagnosis was associated with a higher risk of VTE, but the strength of the associations differed substantially between cancer types.
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Neoplasias/epidemiología , Neoplasias/patología , Tromboembolia Venosa/epidemiología , Anciano , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Medición de Riesgo , Factores de Riesgo , Países Escandinavos y Nórdicos/epidemiología , Factores de Tiempo , Tromboembolia Venosa/diagnósticoRESUMEN
As the world population ages, the comorbidity burden in acute myeloid leukemia (AML) patients increases. Evidence on how to integrate comorbidity measures into clinical decision-making is sparse. We determined the prognostic impact of comorbidity and World Health Organization Performance Status (PS) on achievement of complete remission and mortality in all Danish AML patients treated between 2000 and 2012 overall and stratified by age. Comorbidity was measured using a modified version of the Charlson Comorbidity Index, with separate adjustment for pre-leukemic conditions. Of 2792 patients, 1467 (52.5%) were allocated to intensive therapy. Of these patients, 76% did not have any comorbidities, 19% had one comorbid disease and 6% had two or more comorbidities. Low complete remission rates were associated with poor PS but not with comorbidity. Surprisingly, among all intensive therapy patients, presence of comorbidity was not associated with an increased short-term mortality (adjusted 90 day mortality rate (MR)=1.06 (95% confidence interval (CI)=0.76-1.48)) and, if any, only a slight increase in long-term mortality (91 day-3 year adjusted MR=1.18 (95%CI=0.97-1.44). Poor PS was strongly associated with an increased short- and long-term mortality (adjusted 90 day MR, PS⩾2=3.43 (95%CI=2.30-5.13); adjusted 91 day-3 year MR=1.35 (95%CI=1.06-1.74)). We propose that more patients with comorbidity may benefit from intensive chemotherapy.
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Enfermedades Cardiovasculares/epidemiología , Leucemia Mieloide Aguda/epidemiología , Enfermedades Pulmonares/epidemiología , Sistema de Registros , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/patología , Estudios de Cohortes , Comorbilidad , Dinamarca/epidemiología , Femenino , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/patología , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/patología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Análisis de SupervivenciaAsunto(s)
Sistema del Grupo Sanguíneo ABO , Factor V/genética , Mutación Puntual , Fumar/efectos adversos , Tromboembolia Venosa/epidemiología , Tipificación y Pruebas Cruzadas Sanguíneas , Dinamarca/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Estilo de Vida , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Fumar/epidemiología , Tromboembolia Venosa/sangre , Tromboembolia Venosa/genéticaRESUMEN
BACKGROUND: Large-scale prospective studies are needed to assess whether smoking is associated with venous thromboembolism (VTE) (i.e. deep venous thrombosis and pulmonary embolism) independently of established risk factors. OBJECTIVE: To investigate the association between smoking and the risk of VTE among middle-aged men and women. METHODS: From 1993 to 1997, 27,178 men and 29,875 women, aged 50-64 years and born in Denmark, were recruited into the Danish prospective study 'Diet, Cancer and Health'. During follow-up, VTE cases were identified in the Danish National Patient Registry. Medical records were reviewed and only verified VTE cases were included in the study. Baseline data on smoking and potential confounders were included in gender stratified Cox proportional hazard models to asses the association between smoking and the risk of VTE. The analyses were adjusted for alcohol intake, body mass index, physical activity, and in women also for use of hormone replacement therapy. RESULTS: During follow-up, 641 incident cases of VTE were verified. We found a positive association between current smoking and VTE, with a hazard ratio of 1.52 (95% CI, 1.15-2.00) for smoking women and 1.32 (95% CI, 1.00-1.74) for smoking men, and a positive dose-response relationship. Former smokers had the same hazard as never smokers. CONCLUSIONS: Smoking was an independent risk factor for VTE among middle-aged men and women. Former smokers have the same risk of VTE as never smokers, indicating acute effects of smoking, and underscoring the potential benefits of smoking cessation.
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Fumar/efectos adversos , Tromboembolia Venosa/etiología , Dinamarca/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Factores de Riesgo , Factores Sexuales , Tromboembolia Venosa/epidemiologíaRESUMEN
Many philosophers and medical scientists assume that disease categories or entities used to classify concrete cases of disease, are often defined by disease mechanisms or causal processes. Others suggest that diseases should always be defined in this manner. This paper discusses these standpoints critically and concludes that they are untenable, not only when 'disease mechanism' refers to an objective mechanism, but also when 'mechanism' refers to a pragmatically demarcated part of the total "objective" causal structure of diseases. As an alternative to principles that use the concept of disease mechanism or analogous concepts, a pragmatic approach is suggested and described. This approach has been suggested before, but in problematic or inadequate versions. This paper proposes a version compiled of two "pragmatic principles" and shows that they are much more adequate than the principle of disease mechanism. With reference to a case study of a still ongoing international discussion of various candidates for a classification system for malignant lymphomas, including REAL (Revised European-American Classification of Lymphoid Neoplasms) in which the concept of disease mechanism or analogous concepts plays a very small part, it is shown just how pivotal these two pragmatic principles can be in actual discussions of definitions of diseases. Finally, it is pointed out that with regard to modern philosophy of language it may, at least in some cases, be problematic to distinguish between the two pragmatic principles as they stand.
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Enfermedad/clasificación , Filosofía Médica , Bioética , Dinamarca , Humanos , Linfoma/clasificaciónRESUMEN
PH1 is caused by deficiency of the liver-specific peroxisomal enzyme alanine: glycoxylate aminotransferase (AGT). Early onset with progressive renal failure and systemic oxalosis is typical. We report a case of a 42 year-old man with PH1 in whom liver biopsy and DNA-analysis showed reduced AGT-activity and homozygosity for the polymorphism C154T and the point mutation G630A. The patient seems to respond to pyridoxine treatment. We suggest that clinical suspicion of PH1 be pursued with a diagnostic liver biopsy.