RESUMO
BACKGROUND: Platelets (PLTs) differ in glycolytic activity, resulting in rapid acidification of 'poor' storing PLT concentrates (PCs) in plasma, or depletion of glucose when stored in PLT additive solution (PAS). We aimed to understand why PLT glycolysis rates vary between donors and how this affects storage performance. STUDY DESIGN AND METHODS: Buffy coats from donors <45, 45-70 and >70 years were selected and single-donor PCs in plasma or PAS-E were prepared. PCs were stored for 8 days at 22 ± 2°C and sampled regularly for analysis. Mitochondrial activity was analyzed with an Oroboros oxygraph. Age groups, or subgroups divided into quartiles based on glucose consumption, were analyzed with ANOVA. RESULTS: In each comparison, PCs of the different groups were not different in volume and cellular composition. PLTs with the highest glucose consumption had a higher initial mean platelet volume (MPV) and developed higher CD62P expression and Annexin A5 binding during storage. Higher glycolytic activity in these PLTs was not a compensation for lower mitochondrial ATP production, because mitochondrial ATP-linked respiration of fresh PLTs correlated positively with MPV (R2 = 0.71). Donors of high glucose-consuming PLTs had more health-related issues. Storage properties of PCs from donors over 70 were not significantly different compared to PCs from donors younger than 45 years. CONCLUSIONS: High glucose-consuming PCs developing higher activation levels, not only displayed enhanced mitochondrial activity but were also found to contain larger PLTs, as determined by MPV. Storage performance of PLTs was found to be associated with donor health, but not with donor age.
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Trifosfato de Adenosina , Volume Plaquetário Médio , HumanosRESUMO
BACKGROUND: Metastatic colorectal cancer patients with deficient mismatch repair (dMMR mCRC) benefit from immunotherapy. Interpretation of the single-arm immunotherapy trials is complicated by insignificant survival data during systemic non-immunotherapy. We present survival data on a large, comprehensive cohort of dMMR mCRC patients, treated with or without systemic non-immunotherapy. METHODS: Two hundred and eighty-one dMMR mCRC patients (n = 54 from three prospective Phase 3 CAIRO trials; n = 227 from the Netherlands Cancer Registry). Overall survival was analysed from diagnosis of mCRC (OS), from initiation of first-line (OS1) and second-line (OS2) systemic treatment. Cox regression analysis examined prognostic factors. As comparison for OS 2746 MMR proficient mCRC patients were identified. RESULTS: Of 281 dMMR patients, 62% received first-line and 26% second-line treatment. Median OS was 16.0 months (13.8-19.6) with antitumour therapy and 2.5 months (1.8-3.5) in untreated patients. OS1 was 12.8 months (10.7-15.2) and OS2 6.2 months (5.4-8.9) in treated dMMR patients. Treated dMMR patients had a 7.6-month shorter median OS than pMMR patients. CONCLUSION: Available data from immunotherapy trials lack a control arm with standard systemic treatment. Given the poor outcome compared to the immunotherapy results, our data strongly suggest a survival benefit of immunotherapy in dMMR mCRC patients.
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Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Instabilidade de Microssatélites , Adulto , Idoso , Neoplasias Colorretais/mortalidade , Reparo de Erro de Pareamento de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de SobrevidaRESUMO
Data on the impact of long term treatment with immunomodulatory drugs (IMiD) on health-related quality of life (HRQoL) is limited. The HOVON-87/NMSG18 study was a randomized, phase 3 study in newly diagnosed transplant ineligible patients with multiple myeloma, comparing melphalan-prednisolone in combination with thalidomide or lenalidomide, followed by maintenance therapy until progression (MPT-T or MPR-R). The EORTC QLQ-C30 and MY20 questionnaires were completed at baseline, after three and nine induction cycles and six and 12 months of maintenance therapy. Linear mixed models and minimal important differences were used for evaluation. 596 patients participated in HRQoL reporting. Patients reported clinically relevant improvement in global quality of life (QoL), future perspective and role and emotional functioning, and less fatigue and pain in both arms. The latter being of large effect size. In general, improvement occurred after 6-12 months of maintenance only and was independent of the World Health Organisation performance at baseline. Patients treated with MPR-R reported clinically relevant worsening of diarrhea, and patients treated with MPT-T reported a higher incidence of neuropathy. Patients who remained on lenalidomide maintenance therapy for at least three months reported clinically meaningful improvement in global QoL and role functioning at six months, remaining stable thereafter. There were no clinically meaningful deteriorations, but patients on thalidomide reported clinically relevant worsening in neuropathy. In general, HRQoL improves both during induction and maintenance therapy with immunomodulatory drugs. The side effect profile of treatment did not negatively affect global QoL, but it was, however, clinically relevant for the patients. (Clinicaltrials.gov identifier: NTR1630).
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Lenalidomida/uso terapêutico , Mieloma Múltiplo , Qualidade de Vida , Talidomida/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Melfalan/uso terapêutico , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Prednisona/uso terapêutico , Estudos ProspectivosRESUMO
The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with MPR.
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Melfalan/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Lenalidomida , Quimioterapia de Manutenção , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Prednisona , Talidomida/efeitos adversos , Resultado do Tratamento , Suspensão de TratamentoRESUMO
BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional method to detect frailty in elderly patients. Time saving could be accomplished by identifying those individual items that classify elderly cancer patients at risk for feasibility of chemotherapy and for mortality. MATERIAL AND METHODS: Patients older than 70 years of age were assessed before the first chemotherapy administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual items for feasibility of chemotherapy and mortality were entered in the multivariable logistic regression and Cox-regression models, and a three-item sum scale was constructed: the Geriatric Prognostic Index (GPI). RESULTS: The 494 patients had a median age of 75 years (range 70-92 years). The majority of the patients had malignancies of the digestive tract (41.7%) followed by hematological tumors (22.3%). Three items of the MNA ('psychological distress or acute disease in the past three months', 'neuropsychological problems' and 'using > 3 prescript drugs') independently predicted for feasibility of chemotherapy. Two items of the MNA and one of the GFI ('declining food intake in past 3 months', 'using > 3 prescript drugs', and 'dependence in shopping') independently predicted for mortality. In comparison with patients without any positive item on the three-item GPI, patients with one, two or three positive items had hazard ratios (HRs) of 1.58, 2.32, and 5.58, respectively (all p < 0.001). CONCLUSIONS: With only three items of the MNA, feasibility of chemotherapy can be predicted. The three-item GPI may help to identify elderly cancer patients at elevated risk for mortality.
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Idoso Fragilizado/estatística & dados numéricos , Avaliação Geriátrica/métodos , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Testes Neuropsicológicos , Avaliação Nutricional , Prognóstico , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Comprehensive geriatric assessment (CGA) is a multidimensional method to detect frailty in elderly patients. Time saving could be accomplished by identifying those individual items that classify elderly cancer patients at risk for feasibility of chemotherapy and for mortality. MATERIAL AND METHODS: Patients older than 70 years of age were assessed before the first chemotherapy administration. GA consisted of the Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Predictive individual items for feasibility of chemotherapy and mortality were entered in the multivariable logistic regression and Cox-regression models, and a three-item sum scale was constructed: the Geriatric Prognostic Index (GPI). RESULTS: The 494 patients had a median age of 75 years (range 70-92 years). The majority of the patients had malignancies of the digestive tract (41.7%) followed by hematological tumors (22.3%). Three items of the MNA ('psychological distress or acute disease in the past three months', 'neuropsychological problems' and 'using > 3 prescript drugs') independently predicted for feasibility of chemotherapy. Two items of the MNA and one of the GFI ('declining food intake in past 3 months', 'using > 3 prescript drugs', and 'dependence in shopping') independently predicted for mortality. In comparison with patients without any positive item on the three-item GPI, patients with one, two or three positive items had hazard ratios (HRs) of 1.58, 2.32, and 5.58, respectively (all p < 0.001). CONCLUSIONS: With only three items of the MNA, feasibility of chemotherapy can be predicted. The three-item GPI may help to identify elderly cancer patients at elevated risk for mortality.
Assuntos
Avaliação Geriátrica/métodos , Neoplasias/tratamento farmacológico , Neoplasias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/diagnóstico , Estudos de Viabilidade , Idoso Fragilizado , Humanos , Testes Neuropsicológicos , Avaliação Nutricional , Prognóstico , Análise de Regressão , Estresse Psicológico/diagnósticoAssuntos
Antígenos CD79/genética , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Mutação , Fator 88 de Diferenciação Mieloide/genética , Biomarcadores Tumorais , Biópsia , Humanos , Imuno-Histoquímica , Linfoma Difuso de Grandes Células B/mortalidadeRESUMO
AIM: Anthracycline-induced cardiotoxicity is (partly) mediated by free radical overload. A randomized study was performed in breast cancer patients to investigate whether free radical scavenger super oxide dismutase (SOD) protects against anthracycline-induced cardiotoxicity as measured by changes in echo, electrocardiography and an array of biomarkers. METHOD AND RESULTS: Eighty female, chemotherapy-naïve breast cancer patients (median age 49, range 24-67 years) scheduled for four or five courses of adjuvant 3 weekly doxorubicin plus cyclophosphamide (AC) chemotherapy, were randomly assigned to receive 80 mg PC-SOD (human recombinant SOD bound to lecithin) or placebo, administered intravenously (i.v.) immediately prior to each AC course. The primary end point was protection against cardiac damage evaluated using echocardiography, QT assessments and a set of biochemical markers for myocardial function, oxidative stress and inflammation. Assessments were performed before and during each course of chemotherapy, and at 1, 4 and 9 months after completion of the chemotherapy regimen. In all patients cardiac effects such as increases in NT-proBNP concentration and prolongation of the QTc interval were noticed. There were no differences between the PC-SOD and placebo-treated patients in systolic or diastolic cardiac function or for any other of the biomarkers used to assess the cardiac effects of anthracyclines. CONCLUSION: PC-SOD at a dose of 80 mg i.v. is not cardioprotective in patients with breast carcinoma treated with anthracyclines.
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Antraciclinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Cardiotônicos/uso terapêutico , Sequestradores de Radicais Livres/uso terapêutico , Fosfatidilcolinas/uso terapêutico , Superóxido Dismutase/uso terapêutico , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores/sangue , Neoplasias da Mama/patologia , Cardiotônicos/administração & dosagem , Cardiotônicos/química , Cardiotoxicidade/diagnóstico , Cardiotoxicidade/prevenção & controle , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Esquema de Medicação , Ecocardiografia , Eletrocardiografia , Feminino , Sequestradores de Radicais Livres/administração & dosagem , Sequestradores de Radicais Livres/química , Humanos , Injeções Intravenosas , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Países Baixos , Fragmentos de Peptídeos/sangue , Fosfatidilcolinas/administração & dosagem , Fosfatidilcolinas/química , Superóxido Dismutase/administração & dosagem , Superóxido Dismutase/química , Adulto JovemAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib/uso terapêutico , Dexametasona/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Segunda Neoplasia Primária/tratamento farmacológico , Talidomida/análogos & derivados , Idoso , Idoso de 80 Anos ou mais , Esquema de Medicação , Cálculos da Dosagem de Medicamento , Feminino , Humanos , Lenalidomida , Modelos Logísticos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mieloma Múltiplo/complicações , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Segunda Neoplasia Primária/complicações , Segunda Neoplasia Primária/mortalidade , Segunda Neoplasia Primária/patologia , Recidiva , Análise de Sobrevida , Talidomida/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: Low skeletal muscle index (SMI) in metastatic colorectal cancer (mCRC) patients is associated with poor outcomes. The prognostic impact of SMI changes during consecutive palliative systemic treatments is unknown. METHODS: This is a retrospective analysis of the phase 3 CAIRO3 study. The CAIRO3 study randomized 557 patients between maintenance capecitabine + bevacizumab (CAP-B) or observation, after six cycles capecitabine + oxaliplatin + bevacizumab (CAPOX-B). Upon first disease progression (PD1), CAPOX-B was reintroduced until second progression (PD2). SMI was assessed by computed tomography (CT) (total 1355 scans). SMI and body mass index (BMI) changes were analyzed for three time-periods; p1: during initial CAPOX-B, p2: randomization to PD1, and p3: PD1 to PD2. The association between absolute and change in SMI and BMI (both per 1 standard deviation) during p1-p3, with PD1, PD2, and survival was studied by Cox regression models. RESULTS: This analysis included 450 of the 557 patients randomized in the CAIRO3 study. Mean SMI decreased during p1: mean -0.6 SMI units [95% CI -1.07;-0.26] and p3: -2.2 units [-2.7;-1.8], whereas during p2, SMI increased + 1.2 units [0.8-1.6]. BMI changes did not reflect changes in SMI. SMI loss during p2 and p3 was significantly associated with shorter survival (HR 1.19 [1.09-1.35]; 1.54 [1.31-1.79], respectively). Sarcopenia at PD1 was significantly associated with early PD2 (HR 1.40 [1.10-1.70]). BMI loss independent of SMI loss was only associated with shorter overall survival during p3 (HR 1.35 [1.14-1.63]). CONCLUSIONS: In mCRC patients, SMI loss during palliative systemic treatment was related with early disease progression and reduced survival. BMI did not reflect changes in SMI and could not identify patients at risk of poor outcome during early treatment lines.
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Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Músculo Esquelético/diagnóstico por imagem , Cuidados Paliativos/métodos , Sarcopenia/epidemiologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Índice de Massa Corporal , Ensaios Clínicos Fase III como Assunto , Neoplasias Colorretais/complicações , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Humanos , Estudos Longitudinais , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Intervalo Livre de Progressão , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Fatores de Risco , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Fatores de Tempo , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Increasing evidence suggests that severe skeletal muscle index (SMI) loss (sarcopenia) is associated with poor overall survival in metastatic colorectal cancer patients, but its mechanisms are unknown. We recently found, using data of the randomized phase 3 CAIRO3 study, that SMI loss was related with shorter time to disease progression and overall survival during first-line maintenance treatment with capecitabine + bevacizumab (CAP-B) or observation and during more intensive capecitabine + oxaliplatin + bevacizumab (CAPOX-B) reintroduction treatment. As a potential risk factor for reduced survival, we explored whether sarcopenia and SMI loss were associated with dose-limiting toxicities (DLTs) during CAP-B and CAPOX-B. METHODS: Sarcopenia status and SMI loss were assessed by using consecutive computed tomography scans. DLTs were defined as any dose delay/reduction/discontinuation of systemic treatment because of reported CTCAE (version 3.0) toxicities at the start or during treatment. Poisson regression models were used to study whether sarcopenia and body mass index (BMI) at the start of treatment and SMI and BMI loss during treatment were associated with DLTs. RESULTS: One hundred eighty-two patients (mean age 63.0 ± 8.8 years, 37% female) received CAP-B, and 232 patients (mean age 63.0 ± 9.0 years, 34% female) received CAPOX-B. At the start of CAP-B and CAPOX-B, 54% and 46% of patients were sarcopenic, respectively. Mean BMI was lower in sarcopenic patients, although patients were on average still overweight (sarcopenic vs. non-sarcopenic at the start of CAP-B 25.0 ± 3.9 vs. 26.7 ± 4.1 and CAPOX-B 25.8 ± 3.8 vs. 27.1 ± 3.8 kg/m2 ). Sarcopenia at the start of CAP-B was not associated with DLTs [relative risk 0.87 (95% confidence interval 0.64-1.19)], whereas patients with >2% SMI loss had a significantly higher risk of DLTs [1.29 (1.01-1.66)]. At the start of subsequent CAPOX-B, 25% of patients received a dose reduction, and the risk of dose reduction was significantly higher for patients with preceding SMI loss [1.78 (1.06-3.01)] or sarcopenia [1.75 (1.08-2.86)]. After the received dose reductions, sarcopenia or SMI loss was not significantly associated with a higher risk of DLTs during CAPOX-B [sarcopenia vs. non-sarcopenic: 0.86 (0.69-1.08) and SMI loss vs. stable/gain: 0.83 (0.65-1.07)]. In contrast, BMI (loss) at the start or during either treatment was not associated with an increased risk of DLTs. CONCLUSIONS: In this large longitudinal study in metastatic colorectal cancer patients during palliative systemic treatment, sarcopenia and/or muscle loss was associated with an increased risk of DLTs. BMI was not associated with DLTs and could not detect sarcopenia or SMI loss. Prospective (randomized) studies should reveal whether normalizing chemotherapeutic doses to muscle mass or muscle mass preservation (by exercise and nutritional interventions) increases chemotherapeutic tolerance and improves survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Sarcopenia/etiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/secundário , Relação Dose-Resposta a Droga , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
Levels of factor VIII (FVIII) are associated with the risk of venous thrombosis. The FVIII variation D1241E has been reported to be associated with decreased levels of FVIII. Our objective was to study whether D1241E is associated with levels of FVIII and the risk of venous thrombosis and whether this association is caused by D1241E or another linked variation. We analyzed the association of three FVIII gene haplotypes encoding 1241E (further denoted as HT1, HT3, and HT5) with FVIII levels and thrombosis risk. This analysis was performed in the Leiden Thrombophilia Study (LETS). The control populations of two case-controls studies on arterial thrombosis in men and women, respectively, were used to confirm the effects observed on FVIII:C in the LETS. In men, HT1 was associated with a 6% reduction in FVIII:C and with a reduced risk of venous thrombosis [odds ratio 0.4 (CI95 0.2-0.8)]. Logistic regression showed that the risk reduction was only partially dependent of the reduction in FVIII levels. HT1 showed no effects in women on either FVIII:C or risk of thrombosis. The number of carriers of HT3 and HT5 was too low to make an accurate estimate of the risk of venous thrombosis. Neither HT3 nor HT5 showed effects on levels of FVIII:C. When we consider that all three haplotypes encoding 1241E show different effects on FVIII:C and thrombosis risk, it is possible that D1241E is not the functional variation. However, FVIII gene variations do contribute to both levels of FVIII and the risk of thrombosis.
Assuntos
Fator VIII/genética , Fator VIII/metabolismo , Trombose Venosa/genética , Idoso , Estudos de Casos e Controles , Feminino , Haplótipos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteína C/metabolismo , Fatores de Risco , Análise de Sequência de DNA , Fatores Sexuais , Trombose Venosa/sangueRESUMO
BACKGROUND: To investigate whether low birth weight increases the risk of myocardial infarction later in life in women. METHODS: Nationwide population-based case-control study. Patients and controls: 152 patients with a first myocardial infarction before the age of 50 years in the Netherlands. 568 control women who had not had a myocardial infarction stratified for age, calendar year of the index event, and area of residence. RESULTS: Birth weight in the patient group was significantly lower than in control women (3214 vs. 3370 gram, mean difference -156.3 gram (95%CI -9.5 to -303.1). The odds ratio for myocardial infarction, associated with a birth weight lower than 3000 gram (20th percentile in controls) compared to higher than 3000 gram was 1.7 (95%CI 1.1-2.7), while the odds ratio for myocardial infarction for children with a low birth weight (< 2000 g) compared to a birth weight >/= 2000 g was 2.4 (95%CI 1.0 - 5.8). Both figures did not change after adjustment for putative confounders (age, education level, body mass index, waist-hip ratio, hypertension, diabetes, hypercholesterolemia, smoking, and family history of cardiovascular disease). CONCLUSIONS: Low birth weight is associated with an increased risk of myocardial infarction before age of 50 in Dutch women.
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The age-adjusted International Prognostic Index (IPI) is an important prognostic factor for patients with non-Hodgkin lymphoma (NHL). We investigated whether a geriatric assessment (GA) is of additional prognostic value in NHL. In this prospective cohort study of 44 patients aged 70 years or older with NHL receiving rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), a GA was administered before the start of chemotherapy. GA was composed of the Mini Nutritional Assessment (MNA), Groningen Frailty Indicator (GFI), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Mini Mental State Examination (MMSE) and levels of albumin, creatinine, lactate dehydrogenase (LDH) and hemoglobin. Multivariate analyses were performed using logistic regression and the Cox regression model. After adjustment for sex, age, comorbidity and univariate laboratory values with p ≤ 0.1, abnormal MNA and GFI scores and low hemoglobin level were associated with not being able to complete the intended chemotherapy: odds ratio (OR) 8.29 (95% confidence interval [CI]: 1.24-55.6; p = 0.03), 9.17 (95% CI: 1.51-55.8; p = 0.02) and 5.41 (95% CI: 0.99-29.8; p = 0.05), respectively. Adjusted for sex, age, comorbidity, age-adjusted IPI and univariate laboratory values with p ≤ 0.1, frailty by GFI and low hemoglobin were associated with worse survival, with a hazard ratio (HR) of mortality of 2.55 (95% CI: 1.07-6.10; p = 0.04) and 4.90 (95% CI: 1.76-13.7; p = 0.002), respectively. We conclude that (risk of) malnutrition, measured with the MNA, frailty, measured with the GFI, and low hemoglobin level had additional predictive value for early treatment withdrawal, and GFI and hemoglobin were, independent of the age-adjusted IPI, predictive for an increased mortality risk.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Avaliação Geriátrica/estatística & dados numéricos , Testes Hematológicos/estatística & dados numéricos , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Seguimentos , Avaliação Geriátrica/métodos , Testes Hematológicos/métodos , Humanos , Estimativa de Kaplan-Meier , Leucopenia/induzido quimicamente , Pneumopatias/induzido quimicamente , Masculino , Mucosite/induzido quimicamente , Análise Multivariada , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prognóstico , Estudos Prospectivos , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Sepse/induzido quimicamente , Resultado do Tratamento , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Epidemiological studies have shown an increased risk of venous thrombosis in women taking third-generation oral contraceptives, ie, those containing the progestogens desogestrel or gestodene. This study assesses the risk of ischemic stroke with several types of oral contraceptives. METHODS: A multicenter, population-based, case-control study was performed in 9 Dutch centers in women aged 18 to 49 years. Women with a first ischemic stroke were compared with control women without vascular diseases. The control subjects were recruited by random-digit dialing and were stratified by age, area of residence, and year of stroke. All patients and control subjects filled in a questionnaire about the use of oral contraceptives and risk factors for ischemic stroke. Odds ratios were adjusted for the stratification factors. RESULTS: Two hundred three women with an ischemic stroke and 925 control women were included. The risk of stroke in women using any type of oral contraceptives versus none was 2.3 (95% CI 1.6 to 3.3). Current users of first-generation oral contraceptives had an odds ratio of 1.7 (95% CI 0.7 to 4.4). Low-dose second-generation oral contraceptives increased the risk of stroke 2.4 times (95% CI 1.6 to 3.7), and third-generation oral contraceptives increased the risk of stroke 2.0 times (95% CI 1.2 to 3.5). The risk of stroke in women using third-generation oral contraceptives was not different from that in women using second-generation oral contraceptives (odds ratio 1.0, 95% CI 0.6 to 1.8). CONCLUSIONS: Third-generation oral contraceptives (containing desogestrel or gestodene) confer the same risk of first ischemic stroke as second-generation oral contraceptives (containing levonorgestrel).
Assuntos
Arteriopatias Oclusivas/epidemiologia , Isquemia Encefálica/epidemiologia , Anticoncepcionais Orais , Acidente Vascular Cerebral/epidemiologia , Trombose/epidemiologia , Adolescente , Adulto , Arteriopatias Oclusivas/etiologia , Isquemia Encefálica/etiologia , Estudos de Casos e Controles , Comorbidade , Anticoncepcionais Orais/efeitos adversos , Desogestrel/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Levanogestrel/efeitos adversos , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Norpregnenos/efeitos adversos , Razão de Chances , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Inquéritos e Questionários , Trombose/etiologiaRESUMO
Sero-epidemiological case control studies have observed positive relations between infections with Chlamydia pneumoniae, Helicobacter pylori or cytomegalovirus (CMV) and the occurrence of coronary artery disease (CAD) and stroke. Moreover, positive relations between 'infection burden' and CAD and the role of inflammation have recently been described. However, the relations between infection, inflammation and the occurrence of peripheral arterial disease (PAD) have not been reported so far. We performed a multi-centre population-based case-control study, using serum samples of 228 young female PAD patients and 643 control women to determine IgG antibody titres and C-reactive protein. The odds ratios for PAD in women with serological evidence for infection with C. pneumoniae, H. pylori or CMV were 2.0 (95% CI; 1.3-3.1), 1.6 (95% CI; 1.1-2.2) and 1.6 (95% CI; 1.1-2.3), respectively. The cumulative number of infections was positively related to the risk of PAD; the odds ratio was 1.5 (95% CI; 1.0-2.4), 2.7 (95% CI; 1.6-4.4) and 3.5 (95% CI; 1.5-8.1) for women with one, two or three infections, respectively. This increased risk, related to the 'infection burden', was found again in the subgroup of women with a high CRP level, but not in the subgroup with a low CRP level. Infections might be a causal component in the development of PAD. The risk of PAD is not only related to a single pathogen in particular, but also to the cumulative number of infections. The positive relation between 'infection burden' and PAD was only found in women with a high CRP level, which indicates that inflammation might be involved in the process that leads to PAD.
Assuntos
Infecções por Chlamydophila/epidemiologia , Chlamydophila pneumoniae/isolamento & purificação , Infecções por Citomegalovirus/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori/isolamento & purificação , Doenças Vasculares Periféricas/epidemiologia , Doenças Vasculares Periféricas/microbiologia , Adolescente , Adulto , Distribuição por Idade , Estudos de Casos e Controles , Infecções por Chlamydophila/diagnóstico , Estudos de Coortes , Comorbidade , Intervalos de Confiança , Infecções por Citomegalovirus/diagnóstico , Feminino , Infecções por Helicobacter/diagnóstico , Humanos , Incidência , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Probabilidade , Valores de Referência , Medição de RiscoRESUMO
BACKGROUND: During clinical evaluation of young women with peripheral arterial occlusive disease, we were surprised by the high prevalence of pregnancy loss in women with segmental stenosis confined to the aortoiliac segment. We wondered if increased occurrence of miscarriage is the result of high expression of vascular and obstetrical risk factors in these patients, or if it is related to localization of disease. In a case-control study designed to investigate risk factors for peripheral arterial occlusive disease in young women, we assessed the risk of miscarriage in these patients according to level of obstruction. METHODS: A total of 202 female patients, aged 18-49 years and 466 healthy control women from a population based case-control study, donated venous blood samples and filled out a structured questionnaire concerning classical cardiovascular risk factors and obstetrical history. In all patients, diagnosis of peripheral arterial occlusive disease was confirmed by intra-arterial angiography. Patients were classified into two groups: those with and those without stenosis of the aortoiliac segment (aortoiliac disease). RESULTS: In 77 of the 202 patients (38%) with peripheral arterial occlusive disease, the obstruction was confined to the aortoiliac segment. The occurrence of miscarriage was high (42%) in young women with aortoiliac disease. Compared to healthy controls, the risk of miscarriage increased 3-fold (OR 3.1; 95% CI 1.8-5.6) in these patients. Adjustment for obstetrical and vascular risk factors did not affect the risk estimate. CONCLUSION: This is the first study that identifies aortoiliac disease as a risk factor for pregnancy loss in young women. The risk of miscarriage is increased 3-fold in women with aortoiliac disease. The presence of vascular and obstetrical risk factors did not affect the strength of the association. Pregnancy loss could be the first sign of insufficient aortic circulation in these patients.
Assuntos
Aborto Espontâneo/etiologia , Doenças da Aorta/patologia , Arteriopatias Oclusivas/complicações , Artéria Ilíaca/patologia , Aborto Espontâneo/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Fatores de RiscoRESUMO
PURPOSE: To investigate traditional and novel risk factors (homocysteine and C-reactive protein levels, and exposure to infections) for peripheral arterial disease in young women. SUBJECTS AND METHODS: In a multicenter, population-based, case-control study, 212 young women (mean [+/- SD] age, 48.2 +/- 7.0 years) with peripheral arterial disease and 475 healthy control women (mean age, 45.5 +/- 8.1 years) completed a standardized questionnaire and provided blood samples. Peripheral arterial disease was angiographically confirmed if a stenotic lesion (more than 50% reduction of the lumen) was present in at least one major peripheral artery. Hyperhomocysteinemia was defined as a nonfasting plasma homocysteine level exceeding the 90th percentile of the control group. History of infectious diseases was determined by questionnaire. RESULTS: Elevated C-reactive protein levels were associated with an increased likelihood of peripheral arterial disease (odds ratio [OR] = 3.9; 95% confidence interval [CI]: 1.8 to 8.5 for women in the third quartile; OR = 3.1; 95% CI: 1.4 to 6.8 for women in the fourth quartile; both comparisons with women in the first quartile). Hyperhomocysteinemia was not associated with a significantly increased risk of peripheral arterial disease (OR = 1.6; 95% CI: 0.9 to 3.0). A history of chickenpox, shingles, mumps, pneumonia, chronic bronchitis, peptic ulcer, or periodontitis was independently related to peripheral arterial disease, with adjusted odds ratios varying from 1.7 (95% CI: 1.0 to 3.1) for mumps to 3.4 (95% CI: 1.5 to 7.7) for peptic ulcer. The risk of peripheral arterial disease increased with the number of these infections; exposure to five or more infections increased the odds 3.7-fold (95% CI: 1.7 to 8.2). This association was not affected by the level of C-reactive protein. CONCLUSION: Our results do not support a strong relation between homocysteine and peripheral arterial disease in young women. However, an elevated C-reactive protein level and several types of symptomatic infection were associated with peripheral arterial disease.
Assuntos
Arteriosclerose/etiologia , Proteína C-Reativa/análise , Homocisteína/sangue , Infecções/complicações , Doenças Vasculares Periféricas/etiologia , Arteriosclerose/sangue , Estudos de Casos e Controles , Feminino , Humanos , Perna (Membro)/irrigação sanguínea , Pessoa de Meia-Idade , Razão de Chances , Doenças Vasculares Periféricas/sangue , Fatores de RiscoRESUMO
INTRODUCTION: In general, geriatric assessment (GA) provides the combined information on comorbidity and functional, nutritional and psychosocial status and may be predictive for mortality outcome of cancer patients. The impact of geriatric assessment on the outcome of older patients with colorectal cancer treated with chemotherapy is largely unknown. METHODS: In a prospective study, 143 patients with colorectal cancer who were 70years and older were assessed before chemotherapy by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). RESULTS: Fifty-four (38%) patients received adjuvant chemotherapy and 89 (62%) patients received palliative chemotherapy. Malnutrition and frailty were prevalent in 39 (27%, assessed by MNA) and 34 (24%, by GFI) patients, respectively; whereas cognitive impairment was prevalent in 19 (13%, by IQCODE) and 11 (8%, by MMSE) patients, respectively. In patients with palliative chemotherapy, poor MNA scores were associated with receiving less than 4cycles of chemotherapy (p=0.008). Poor MNA and GFI scores were associated with increased hazard ratios (HR) for mortality for patients with palliative chemotherapy: HR=2.76 (95% confidence interval [CI]: 1.60-4.77; p<0.001) and HR=2.72 (95% CI: 1.58-4.69; p<0.001), respectively, after adjustment for several clinical parameters. CONCLUSIONS: Malnutrition and frailty were strongly associated with an increased mortality risk in patients who underwent palliative chemotherapy. Furthermore, a poor score on MNA was predictive for less tolerance of chemotherapy. Our findings may help the oncologist in future decision making and advice for elderly patients with colorectal cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/mortalidade , Idoso Fragilizado/estatística & dados numéricos , Desnutrição/mortalidade , Neoplasias Retais/mortalidade , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante/mortalidade , Transtornos Cognitivos/complicações , Transtornos Cognitivos/mortalidade , Neoplasias do Colo/tratamento farmacológico , Feminino , Humanos , Masculino , Avaliação Nutricional , Cuidados Paliativos/estatística & dados numéricos , Estudos Prospectivos , Neoplasias Retais/tratamento farmacológico , Fatores de RiscoRESUMO
OBJECTIVES: We investigated whether elevated levels of factor VIII, IX and XI is associated with myocardial infarction (MI) in young women. In addition, we studied ABO blood group, von Willebrand factor (VWF) and C-reactive protein (CRP). METHODS AND RESULTS: We compared 200 women with MI before age 49 years with 626 controls from a population-based case-control study. Mean levels of factor VIII activity (VIII), von Willebrand factor antigen (VWF), factor IX activity (IX) were higher in patients (133, 134 and 132 IU/dL) than in controls (111, 107 and 120 IU/dL, respectively). Mean levels of factor XI (XI) were equal in patients (114 IU/dL) and controls (113 IU/dL). The odds ratio (OR) for MI for blood group non-O vs. O was 1.6 [95% confidence interval (CI) 1.1-2.3]. The OR adjusted for age, index year and area of residence for the highest quartile >150 IU/dL of factor VIII was 2.7 (95% CI 1.6-4.6), of VWF 4.7 (95% CI 2.3-9.7), of factor IX 2.6 (95% CI 1.3-5.4) and of factor XI 0.9 (95% CI 0.5-1.4), all compared with the lowest quartile <100 IU/dL. CONCLUSIONS: Non-O blood group, high VWF, factor VIII and factor IX levels are associated with an increased risk of MI in young women, while high factor XI levels are not.