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1.
Leukemia ; 38(4): 840-850, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38297135

ABSTRACT

A randomized phase-II study was performed in low/int-1 risk MDS (IPSS) to study efficacy and safety of lenalidomide without (arm A) or with (arm B) ESA/G-CSF. In arm B, patients without erythroid response (HI-E) after 4 cycles received ESA; G-CSF was added if no HI-E was obtained by cycle 9. HI-E served as primary endpoint. Flow cytometry and next-generation sequencing were performed to identify predictors of response. The final evaluation comprised 184 patients; 84% non-del(5q), 16% isolated del(5q); median follow-up: 70.7 months. In arm A and B, 39 and 41% of patients achieved HI-E; median time-to-HI-E: 3.2 months for both arms, median duration of-HI-E: 9.8 months. HI-E was significantly lower in non-del(5q) vs. del(5q): 32% vs. 80%. The same accounted for transfusion independency-at-week 24 (16% vs. 67%), but similar in both arms. Apart from presence of del(5q), high percentages of bone marrow lymphocytes and progenitor B-cells, a low number of mutations, absence of ring sideroblasts, and SF3B1 mutations predicted HI-E. In conclusion, lenalidomide induced HI-E in patients with non-del(5q) and del(5q) MDS without additional effect of ESA/G-CSF. The identified predictors of response may guide application of lenalidomide in lower-risk MDS in the era of precision medicine. (EudraCT 2008-002195-10).


Subject(s)
Hematinics , Myelodysplastic Syndromes , Humans , Lenalidomide/pharmacology , Hematinics/pharmacology , Erythropoiesis , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Granulocyte Colony-Stimulating Factor/pharmacology , Chromosome Deletion , Chromosomes, Human, Pair 5/genetics , Treatment Outcome
2.
Ann Oncol ; 28(9): 2128-2134, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28911067

ABSTRACT

BACKGROUND: The phase 3 CAIRO3 study showed that capecitabine plus bevacizumab (CAP-B) maintenance treatment after six cycles capecitabine, oxaliplatin, and bevacizumab (CAPOX-B) in metastatic colorectal cancer (mCRC) patients is effective, without compromising quality of life. In this post hoc analysis with updated follow-up and data regarding sidedness, we defined subgroups according to RAS/BRAF mutation status and mismatch repair (MMR) status, and investigated their influence on treatment efficacy. PATIENTS AND METHODS: A total of 558 patients with previously untreated mCRC and stable disease or better after six cycles CAPOX-B induction treatment were randomised to either CAP-B maintenance treatment (n = 279) or observation (n = 279). Upon first progression, patients were to receive CAPOX-B reintroduction until second progression (PFS2, primary end point). We centrally assessed RAS/BRAF mutation status and MMR status, or used local results if central assessment was not possible. Intention-to-treat stratified Cox models adjusted for baseline covariables were used to examine whether treatment efficacy was modified by RAS/BRAF mutation status. RESULTS: RAS, BRAF mutations, and MMR deficiency were detected in 240/420 (58%), 36/381 (9%), and 4/279 (1%) patients, respectively. At a median follow-up of 87 months (IQR 69-97), all mutational subgroups showed significant improvement from maintenance treatment for the primary end point PFS2 [RAS/BRAF wild-type: hazard ratio (HR) 0.57 (95% CI 0.39-0.84); RAS-mutant: HR 0.74 (0.55-0.98); V600EBRAF-mutant: HR 0.28 (0.12-0.64)] and secondary end points, except for the RAS-mutant subgroup regarding overall survival. Adjustment for sidedness instead of primary tumour location yielded comparable results. Although right-sided tumours were associated with inferior prognosis, both patients with right- and left-sided tumours showed significant benefit from maintenance treatment. CONCLUSIONS: CAP-B maintenance treatment after six cycles CAPOX-B is effective in first-line treatment of mCRC across all mutational subgroups. The benefit of maintenance treatment was most pronounced in patients with RAS/BRAF wild-type and V600EBRAF-mutant tumours. CLINICALTRIALS.GOV NUMBER: NCT00442637.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/administration & dosage , Capecitabine/administration & dosage , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Adult , Aged , Aged, 80 and over , Brain Neoplasms/genetics , Colorectal Neoplasms/pathology , DNA Mismatch Repair/genetics , Disease-Free Survival , Female , Humans , Male , Middle Aged , Mutation , Neoplasm Metastasis , Neoplastic Syndromes, Hereditary/genetics , Observation , Proto-Oncogene Proteins B-raf/genetics , Treatment Outcome , ras Proteins/genetics
3.
Eur J Cancer ; 75: 204-212, 2017 04.
Article in English | MEDLINE | ID: mdl-28237866

ABSTRACT

AIM: Capecitabine and bevacizumab (CAP-B) maintenance therapy has shown to be more effective compared with observation in metastatic colorectal cancer patients achieving stable disease or better after six cycles of first-line capecitabine, oxaliplatin, bevacizumab treatment in terms of progression-free survival. We evaluated the cost-effectiveness of CAP-B maintenance treatment. METHODS: Decision analysis with Markov modelling to evaluate the cost-effectiveness of CAP-B maintenance compared with observation was performed based on CAIRO3 study results (n = 558). An additional analysis was performed in patients with complete or partial response. The primary outcomes were the incremental cost-effectiveness ratio (ICER) defined as the additional cost per life year (LY) and quality-adjusted life years (QALY) gained, calculated from EQ-5D questionnaires and literature and LYs gained. Univariable sensitivity analysis was performed to assess the influence of input parameters on the ICER, and a probabilistic sensitivity analysis represents uncertainty in model parameters. RESULTS: CAP-B maintenance compared with observation resulted in 0.21 QALYs (0.18LYs) gained at a mean cost increase of €36,845, yielding an ICER of €175,452 per QALY (€204,694 per LY). Varying the difference in health-related quality of life between CAP-B maintenance and observation influenced the ICER most. For patients achieving complete or partial response on capecitabine, oxaliplatin, bevacizumab induction treatment, an ICER of €149,300 per QALY was calculated. CONCLUSION: CAP-B maintenance results in improved health outcomes measured in QALYs and LYs compared with observation, but also in a relevant increase in costs. Despite the fact that there is no consensus on cost-effectiveness thresholds in cancer treatment, CAP-B maintenance may not be considered cost-effective.


Subject(s)
Antineoplastic Agents/economics , Bevacizumab/economics , Capecitabine/economics , Colorectal Neoplasms/economics , Antineoplastic Agents/therapeutic use , Bevacizumab/therapeutic use , Capecitabine/therapeutic use , Colorectal Neoplasms/drug therapy , Cost-Benefit Analysis , Drug Costs , Hospitalization/economics , Humans , Markov Chains , Netherlands , Quality of Life , Quality-Adjusted Life Years
4.
Colorectal Dis ; 15(10): e582-91, 2013.
Article in English | MEDLINE | ID: mdl-23679338

ABSTRACT

AIM: The study included investigation of factors determining suboptimal adjuvant chemotherapy of patients diagnosed with Stage III colon cancer. METHOD: All 606 patients diagnosed with Stage III colon cancer between 2006 and 2008 in the western part of the Netherlands were included. Patient [gender, age, comorbidity and socio-economic status (SES)], tumour (location, stage and grade) and treatment (emergency surgery, laparoscopic surgery, reoperation, hospital stay and multidisciplinary meeting) factors were examined in logistic regression analyses predicting a complicated postoperative period and omission, delay and discontinuation of adjuvant chemotherapy. RESULTS: Overall, 27% of all patients experienced a complicated postoperative period, which was independently associated with emergency surgery, older age, multiple comorbidity, male gender and poor tumour grade. Of patients who survived this period, 60% received chemotherapy. Chemotherapy was omitted more often in women, the elderly and in patients with Stage IIIB, reoperation, prolonged hospital stay and (borderline) after open surgery. Of patients who received chemotherapy, 86% started within 8 weeks after surgery. Patients with a higher SES, reoperation and prolonged hospital stay had a higher probability of a delayed start. Sixty-seven per cent of patients completed their chemotherapy. For women, elderly patients and patients with prolonged hospital stay a higher probability of discontinuation was noted. CONCLUSION: Age was the most important predictive factor for receiving adjuvant chemotherapy. However, at all ages, complicated postoperative recovery negatively influenced the administration of chemotherapy to Stage III colon cancer patients, as well as a timely start and completion of chemotherapy.


Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma/drug therapy , Carcinoma/surgery , Colonic Neoplasms/drug therapy , Colonic Neoplasms/surgery , Postoperative Complications , Age Factors , Aged , Antineoplastic Agents/adverse effects , Carcinoma/pathology , Chemotherapy, Adjuvant , Colonic Neoplasms/pathology , Comorbidity , Emergencies , Female , Humans , Length of Stay , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Reoperation , Sex Factors , Social Class , Time Factors , Withholding Treatment
5.
Breast ; 22(5): 753-60, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23414850

ABSTRACT

INTRODUCTION: The prognostic value of geriatric assessment in older patients with breast cancer treated with chemotherapy is largely unknown. METHODS: Fifty-five patients with advanced breast cancer aged 70 years or older were assessed by Mini Nutritional Assessment (MNA), Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), Groningen Frailty Indicator (GFI) and Mini Mental State Examination (MMSE). Levels of albumin, hemoglobin, creatinine and lactate dehydrogenase were measured. Patients completing at least four cycles of chemotherapy were reassessed by GFI and MMSE and mortality was evaluated using Cox regression analysis. RESULTS: The mean age was 76 year (SD 4.8). Inferior MNA and GFI scores were associated with increased hazard ratios for mortality: 3.05 (95% confidence interval [CI]: 1.44-6.45; p = 0.004) and 3.40 (95% CI: 1.62-7.10; p = 0.001), respectively. Physical aspects of frailty worsened during the course of chemotherapy. Laboratory values were not associated with assessment scores nor were they predictive for mortality. CONCLUSIONS: Malnutrition and frailty, rather than cognitive impairment and laboratory values, were associated with an increased mortality risk in these elderly breast cancer patients with advanced breast cancer.


Subject(s)
Breast Neoplasms/drug therapy , Geriatric Assessment , Aged , Aged, 80 and over , Antineoplastic Agents/therapeutic use , Breast Neoplasms/blood , Breast Neoplasms/complications , Breast Neoplasms, Male/blood , Breast Neoplasms, Male/drug therapy , Breast Neoplasms, Male/mortality , Cognition Disorders/complications , Creatinine/blood , Female , Hemoglobins/metabolism , Humans , Kaplan-Meier Estimate , L-Lactate Dehydrogenase/blood , Male , Malnutrition/complications , Prognosis , Proportional Hazards Models , Serum Albumin/metabolism
7.
Prenat Diagn ; 26(8): 719-24, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16752436

ABSTRACT

BACKGROUND: We have offered, for the first time in The Netherlands, carrier diagnostics for hemoglobinopathies (HbP) to early pregnant women. The aim of this study was to establish whether carrier analysis would be welcome by the public and feasible at the outpatient level. METHOD: One hundred and thirty-nine randomly selected women were informed and offered basic carrier diagnostics at the first pregnancy control. RESULTS: Carrier diagnostics was accepted by 136 women (97.8%). The population consisted of 31% of recent immigrants and 69% of native Dutch. One carrier of HbS and one of beta-thalassemia were found, both among the group of the recent immigrants. In both cases, partners were tested excluding a couple at risk. In addition, five carriers of alpha(+)-thalassemia were diagnosed at the molecular level, one of them in the native Dutch population. Basic carrier analysis was done both at the Hospital Laboratory and at the Reference Laboratory. No discrepancies were found. CONCLUSIONS: This pilot study shows that (1) as predicted the prevalence of risk-related HbP and of alpha(+)-thalassemia is high in the immigrant population. (2) The compliance with carrier analysis in both native Dutch and immigrants is virtually total and (3) carrier diagnosis in early pregnancy and partner analysis in Hospital Laboratories is possible and is an effective tool for primary prevention of HbP in The Netherlands.


Subject(s)
Genetic Testing/methods , Hemoglobinopathies/prevention & control , Heterozygote , Patient Acceptance of Health Care , Prenatal Diagnosis/methods , Adult , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/epidemiology , Anemia, Sickle Cell/prevention & control , Female , Hemoglobinopathies/diagnosis , Hemoglobinopathies/epidemiology , Humans , Netherlands/epidemiology , Pilot Projects , Pregnancy , Prevalence , alpha-Thalassemia/diagnosis , alpha-Thalassemia/epidemiology , alpha-Thalassemia/prevention & control , beta-Thalassemia/diagnosis , beta-Thalassemia/epidemiology , beta-Thalassemia/prevention & control
8.
J Thromb Haemost ; 3(6): 1213-7, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15946211

ABSTRACT

BACKGROUND: The role of inherited prothrombotic conditions, including factor V Leiden (FV G1691A), prothrombin G20210A, and the methylenetetrahydrofolate reductase (MTHFR) C677T genotype, in the pathogenesis of ischemic stroke is not well established. The effects of these factors may be potentiated by the use of oral contraceptives, analogous to observations in venous thrombosis. METHODS: Patients (n = 193) were women aged 20-49 years with ischemic stroke. Controls (n = 767) were women without arterial thrombosis stratified for age, calendar year of the index event, and residence. The relative risk of ischemic stroke was estimated with unconditional logistic regression, adjusted for stratification variables. FINDINGS: Factor V Leiden and MTHFR 677TT were more common in patients than in controls [odds ratio (OR): 1.8; 95% confidence interval (CI): 0.9-3.6 respectively OR: 1.5; 95% CI: 0.9-2.6]. The frequency of prothrombin G20210A was similar in cases and controls. Carriers of FV Leiden using oral contraceptives had a 11.2-fold (95% CI: 4.3-29.0) higher risk of ischemic stroke than women without either risk factor. Women with MTHFR 677TT using oral contraceptives had a 5.4-fold (95% CI: 2.4-12.0) higher risk than women without these risk factors. INTERPRETATION: These data suggest that carriers of FV Leiden or MTHFR 677TT who use oral contraceptives have an increased risk of ischemic stroke. When these findings are confirmed, a cost-effectiveness analysis should indicate whether ischemic stroke could be prevented with genetic testing before the start of oral contraceptives.


Subject(s)
Contraceptives, Oral/adverse effects , Stroke/genetics , Thrombophilia/complications , Adult , Brain Ischemia , Case-Control Studies , Factor V , Female , Heterozygote , Humans , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Middle Aged , Regression Analysis , Risk Factors , Stroke/epidemiology , Stroke/etiology , Thrombophilia/epidemiology , Thrombophilia/genetics
9.
J Thromb Haemost ; 2(1): 35-41, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14717963

ABSTRACT

In young women data are limited about the association between myocardial infarction (MI) and hyperhomocysteinemia, low folate or methylenetetrahydrofolate reductase (MTHFR) genotypes. The effect of oral contraceptive (OC) use on plasma homocysteine levels is not clear. We assessed the association between hyperhomocysteinemia, low folate, MTHFR 677TT mutation and risk of MI, and we investigated the effect of OC use on homocysteine levels in controls. In 181 patients with a first MI and 601 controls 18-49 years of age from a population-based case-control study, non-fasting blood samples were available. The homozygote mutant allele (TT) was detected in 12% of the patients and in 10% of controls. The odds ratio (OR) for MI in TT patients compared with the wild-type (CC) controls was 1.3 [95% confidence interval (CI) 0.8, 2.3]. For all MTHFR genotypes combined, the OR for MI in the lowest quartile of folate (<5.4 nmol L-1) compared with the highest quartile (>10.4 nmol L-1) was 3.0 (95% CI 1.7, 5.1). A 2-fold increased risk of MI was found in women with the TT genotype who had folate levels below the median of 7.4 nmol L-1 compared with CC genotype and folate levels above the median (OR = 2.0; 95% CI 1.0, 3.7). Mean homocysteine levels were 12.2 micromol L-1 in OC users and 12.3 micromol L-1 in non-users. Only at the 97.5 percentile (cut-off 21.0 micromol L-1) was the adjusted OR for higher vs. lower homocysteine levels increased by 2.8-fold (95% CI 1.2, 6.8). Low folate is a risk factor for MI, particularly in women with the MTHFR 677TT genotype. Homocysteine levels were not influenced by OC use.


Subject(s)
Folic Acid/blood , Homocysteine/blood , Methylenetetrahydrofolate Reductase (NADPH2)/genetics , Myocardial Infarction/etiology , Adolescent , Adult , Case-Control Studies , Contraceptives, Oral/therapeutic use , Female , Genetic Variation , Genotype , Humans , Hyperhomocysteinemia/complications , Middle Aged , Myocardial Infarction/blood , Myocardial Infarction/enzymology , Myocardial Infarction/genetics , Risk Factors , Vitamin B 12/blood
10.
J Thromb Haemost ; 1(7): 1371-80, 2003 Jul.
Article in English | MEDLINE | ID: mdl-12871270

ABSTRACT

Hundreds of millions of women worldwide use either oral contraceptives or postmenopausal hormone replacement. The use of oral contraceptives leads to an increased risk of venous thrombosis, of myocardial infarction, of stroke and of peripheral artery disease, the risks of which are highest during the first year of use. Women with coagulation abnormalities have a higher risk of venous thrombosis when they use oral contraceptives (or postmenopausal hormones) than women without these abnormalities. The risk of venous thrombosis is also higher for preparations containing desogestrel or gestodene (third-generation progestogens) than for those containing levonorgestrel (second-generation progestogens). A previous thrombosis as well as obesity also increase the risk of oral contraceptive-related thrombosis. Hormone replacement therapy increases the risk of venous thrombosis, and has no beneficial, and possibly even a detrimental, effect on the risk of arterial disease. The risk of arterial disease in oral contraceptive users and users of hormone replacement therapy is at most weakly affected by the presence of prothrombotic abnormalities.


Subject(s)
Estrogens/physiology , Progestins/physiology , Thrombosis/metabolism , Contraceptives, Oral/adverse effects , Female , Hormone Replacement Therapy/adverse effects , Humans , Myocardial Infarction/pathology , Risk , Venous Thrombosis/pathology
11.
J Thromb Haemost ; 1(3): 439-44, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12871447

ABSTRACT

With regard to oral contraceptives, much research has concentrated on venous thrombosis and on the coronary and cerebral forms of atherosclerotic disease, while peripheral arterial disease (PAD) has received little attention. In this case-control study, we assessed oral contraceptive use and the risk of PAD in young women using a population-based case-control study. The women were 18-49 years of age, and had been admitted to a collaborating hospital between January 1990 and October 1995, and had a diagnosis of PAD. Participants were patients with PAD (n = 152), and control women (n = 925), identified by random digit dialing. The diagnosis of PAD was based almost exclusively on intra-arterial angiography. Patients and control subjects filled out the same structured questionnaire, which included questions on medical history, cardiovascular risk factors, and contraceptive use. The adjusted odds ratio for PAD in women using any type of oral contraceptives vs. no use, was 3.8 (95% CI 2.4-5.8). When first generation oral contraceptive use was compared with no use, the odds ratio was 8.7 (95% CI 3.6-21.3). For second and third generation oral contraceptives, the adjusted odds ratios (compared with non-users) were 2.6 (95% CI 1.4-4.9) and 3.0 (95% CI 1.4-6.6), respectively. This is the first study on oral contraceptive use and PAD in humans. All types of oral contraceptives were associated with an increased risk of PAD.


Subject(s)
Contraceptives, Oral/adverse effects , Peripheral Vascular Diseases/chemically induced , Adult , Arterial Occlusive Diseases/chemically induced , Case-Control Studies , Dose-Response Relationship, Drug , Estrogens/adverse effects , Female , Humans , Middle Aged , Netherlands/epidemiology , Odds Ratio , Progestins/adverse effects , Risk Factors , Surveys and Questionnaires
13.
Eur J Clin Invest ; 32(8): 549-55, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12190953

ABSTRACT

BACKGROUND: Recent studies have suggested that a chronic infection with Helicobacter pylori might be an independent risk factor for atherosclerosis. However, a direct role in atherogenesis is not plausible, since the bacterium has not been isolated from atherosclerotic lesions. An indirect mechanism that could link H. pylori with atherosclerosis might be through an increase in plasma homocysteine concentration caused by deficiencies of vitamin B12 and folate in plasma. MATERIALS AND METHODS: In 150 female patients with peripheral arterial disease (PAD) and in 412 healthy control women from a nation-wide population-based case-control study, blood samples were collected to determine the antibody titre against H. pylori and to measure plasma homocysteine, folate and vitamin B12 levels. First, the odds ratio for PAD in women with a positive antibody titre against H. pylori was calculated and adjusted for homocysteine level. Secondly, mean concentrations of vitamin B12, folate and homocysteine were compared in healthy controls with a positive or negative antibody titre against H. pylori. Thirdly, the relation between H. pylori and PAD in individuals with a normal or high homocysteine level was investigated. RESULTS: A positive immunoglobulin G antibody titre against H. pylori was found in 42% of the PAD patients and in 27% of the controls. The age- and socio-economic-status (SES) adjusted odds ratio for PAD was 1.5 (95%CI; 1.0-2.2). Additional adjustment for homocysteine plasma concentration did not essentially change the odds ratio. Secondly, among the healthy controls, the homocysteine plasma concentration did not depend on the immunoglobulin G titre, neither did the folate plasma concentration. The concentration of vitamin B12 was slightly higher in women with a positive titre. Thirdly, H. pylori infection was a risk factor for PAD in subjects with a normal homocysteine concentration [OR 2.0 (95%CI 1.3-3.1)]. CONCLUSIONS: This study shows a relationship between a positive immunoglobulin G antibody titre against H. pylori and PAD in young women. Moreover, this study does not support the hypothesis that H. pylori infection is related to atherosclerosis via an increase in plasma homocysteine concentration.


Subject(s)
Arteriosclerosis/microbiology , Helicobacter Infections/complications , Helicobacter pylori , Homocysteine/blood , Peripheral Vascular Diseases/microbiology , Adolescent , Adult , Age Factors , Antigens, Bacterial/blood , Arteriosclerosis/blood , Arteriosclerosis/immunology , Case-Control Studies , Chronic Disease , Female , Folic Acid Deficiency/blood , Helicobacter Infections/blood , Helicobacter Infections/immunology , Helicobacter pylori/immunology , Humans , Immunoglobulin G/blood , Middle Aged , Odds Ratio , Peripheral Vascular Diseases/blood , Peripheral Vascular Diseases/immunology , Risk Factors , Socioeconomic Factors , Vitamin B 12 Deficiency/blood
14.
N Engl J Med ; 345(25): 1787-93, 2001 Dec 20.
Article in English | MEDLINE | ID: mdl-11752354

ABSTRACT

BACKGROUND: An association between the use of oral contraceptives and the risk of myocardial infarction has been found in some, but not all, studies. We investigated this association, according to the type of progestagen included in third-generation (i.e., desogestrel or gestodene) and second-generation (i.e., levonorgestrel) oral contraceptives, the dose of estrogen, and the presence or absence of prothrombotic mutations METHODS: In a nationwide, population-based, case-control study, we identified and enrolled 248 women 18 through 49 years of age who had had a first myocardial infarction between 1990 and 1995 and 925 control women who had not had a myocardial infarction and who were matched for age, calendar year of the index event, and area of residence. Subjects supplied information on oral-contraceptive use and major cardiovascular risk factors. An analysis for factor V Leiden and the G20210A mutation in the prothrombin gene was conducted in 217 patients and 763 controls RESULTS: The odds ratio for myocardial infarction among women who used any type of combined oral contraceptive, as compared with nonusers, was 2.0 (95 percent confidence interval, 1.5 to 2.8). The adjusted odds ratio was 2.5 (95 percent confidence interval, 1.5 to 4.1) among women who used second-generation oral contraceptives and 1.3 (95 percent confidence interval, 0.7 to 2.5) among those who used third-generation oral contraceptives. Among women who used oral contraceptives, the odds ratio was 2.1 (95 percent confidence interval, 1.5 to 3.0) for those without a prothrombotic mutation and 1.9 (95 percent confidence interval, 0.6 to 5.5) for those with a mutation CONCLUSIONS: The risk of myocardial infarction was increased among women who used second-generation oral contraceptives. The results with respect to the use of third-generation oral contraceptives were inconclusive but suggested that the risk was lower than the risk associated with second-generation oral contraceptives. The risk of myocardial infarction was similar among women who used oral contraceptives whether or not they had a prothrombotic mutation.


Subject(s)
Contraceptives, Oral/adverse effects , Myocardial Infarction/chemically induced , Adolescent , Adult , Case-Control Studies , Desogestrel/adverse effects , Ethinyl Estradiol/adverse effects , Factor V/genetics , Female , Humans , Levonorgestrel/adverse effects , Logistic Models , Middle Aged , Myocardial Infarction/genetics , Norpregnenes/adverse effects , Odds Ratio , Point Mutation , Prothrombin/genetics , Risk Factors , Smoking/adverse effects
15.
Ned Tijdschr Geneeskd ; 144(17): 797-800, 2000 Apr 22.
Article in Dutch | MEDLINE | ID: mdl-10800549

ABSTRACT

The selection of a valid control group is important in case control studies and has therefore generated a fair amount of discussion in the epidemiologic literature. The proposal of the study usually determines the type of control group that should be selected. It is possible to select population controls, hospital controls, friends or relatives of patients or a variant of these. Each method has specific advantages and disadvantages. Random-digit dialing can be used to select population controls by telephone. This method is a valuable alternative when no registry exists.


Subject(s)
Case-Control Studies , Research Design/standards , Selection Bias , Epidemiologic Methods , Humans , Reproducibility of Results
16.
Br J Haematol ; 100(2): 380-2, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9488630

ABSTRACT

We report a patient with congenital homozygous factor V deficiency in whom a large pseudotumour in the right upper leg was successfully surgically excised under continuous substitution with fresh-frozen plasma.


Subject(s)
Factor V Deficiency/complications , Hematoma/surgery , Adult , Blood Loss, Surgical , Diagnosis, Differential , Factor V Deficiency/congenital , Hematoma/complications , Humans , Male , Neoplasms/complications , Plasma Exchange , Thigh
17.
Clin Endocrinol (Oxf) ; 44(6): 643-9, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8759176

ABSTRACT

OBJECTIVE: The significance of mild hypercholesterolaemia in subclinical hypothyroidism and whether there is beneficial reduction after thyroxine replacement, remain controversial. We aimed to describe the association between hypercholesterolaemia and subclinical hypothyroidism, and to quantify the effect of thyroid substitution therapy by an analysis of previously published intervention studies. DATA SOURCES: Intervention studies cited in the Medline database from January 1976 until January 1995, with index terms cholesterol, hypercholesterolaemia, hyperlipidaemia, thyrotrophin (TSH), hypothyroidism, thyroid and human. A total of 148 studies were reviewed. DATA EXTRACTION: We recorded the year of publication, study design, number of patients enrolled, mean age, duration of thyroid substitution, normal range of TSH levels, TSH levels pre and post-substitution treatment and total cholesterol in plasma before and after treatment. DATA ANALYSIS: (1) Qualitative description of studies on the relationship between hypercholesterolaemia and hypothyroidism, both subclinical and clinical. (2) Precision weighted pooled estimates of the effect of thyroid substitution therapy on the plasma levels of total cholesterol, in patients with subclinical and overt hypothyroidism. RESULTS: Subclinical hypothyroidism was two to three times more frequent in people with an elevated total plasma cholesterol. In addition, the total plasma cholesterol levels were slightly elevated in patients with subclinical dysfunction of the thyroid. Thyroid substitution therapy in patients with subclinical hypothyroidism, restoring the TSH levels to normal, decreased total cholesterol by 0.4 mmol/l (95% confidence interval (Cl) 0.2-0.6 mmol/l) independently of the initial plasma level. The effect of thyroid substitution therapy on HDL-cholesterol in patients with subclinical hypothyroidism was not consistent. The effect of thyroid substitution in patients with overt hypothyroidism was highly dependent on the pretreatment levels of total cholesterol. In these patients substitution therapy decreased total cholesterol by 1.2 mmol/l (95% Cl 0.9-1.5 mmol/l) when the plasma levels were elevated up to 8 mmol/l, and by 3.4 mmol/l (95% Cl 3.0-3.7) when plasma levels were higher than 8 mmol/l. The high density lipoprotein (HDL)-cholesterol level decreased and amounted to 0.16 mmol/l (95% Cl 0.07-0.24). CONCLUSIONS: Thyroid substitution treatment in patients with hypercholesterolaemia and subclinical hypothyroidism decreases total plasma cholesterol by 0.4 mmol/l, but plasma levels remain elevated in most patients. Further treatment with dietary restriction and cholesterol synthesis inhibitors should then be considered.


Subject(s)
Hypercholesterolemia/drug therapy , Hypothyroidism/drug therapy , Thyroxine/therapeutic use , Adult , Cholesterol, HDL/blood , Female , Humans , Hypercholesterolemia/blood , Hypercholesterolemia/complications , Hypothyroidism/blood , Hypothyroidism/complications , Thyrotropin/blood
20.
Nephrol Dial Transplant ; 10(7): 1240-3, 1995.
Article in English | MEDLINE | ID: mdl-7478133

ABSTRACT

Aspergillus peritonitis is a rare complication of continuous ambulatory peritoneal dialysis. The case is described of a 68-year-old man in whom Aspergillus fumigatus was isolated from the peritoneal dialysate after recurrent peritonitis with Gram-negative rods in association with diverticulosis. Treatment consisting of removal of the catheter and intravenous administration of amphotericin B followed by oral itraconazole was successful. A review of the sparse literature (12 cases) displays uncertainties regarding diagnostic awareness, culture diagnosis, and therapeutic management. Next to institution of appropriate antifungal therapy, early removal of the peritoneal dialysis catheter is recommended, as delayed removal of the catheter appears to be associated with increased mortality and morbidity.


Subject(s)
Aspergillosis , Peritonitis/microbiology , Administration, Oral , Aged , Amphotericin B/therapeutic use , Aspergillosis/drug therapy , Aspergillosis/etiology , Humans , Infusions, Intravenous , Itraconazole/therapeutic use , Male , Peritoneal Dialysis, Continuous Ambulatory/adverse effects
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