Prevention and treatment of venous thromboembolism--International Consensus Statement.

The aim of this document is to provide a clear and concise account of the evidence regarding efficacy or harm for various methods available to prevent and manage venous thromboembolism (VTE).

The use of intrapartum electronic fetal heart rate monitoring: a national survey.

This study describes the use of intrapartum electronic fetal monitoring in Ireland. Electronic fetal monitoring (EFM) has become routine in the assessment of fetal wellbeing during labour. Current evidence indicates that the routine use of EFM leads to an increased caesarean section and operative vaginal delivery rate and a reduction in the rate of neonatal seizures. Practices and service provision related to the use and interpretation of and educational provision for electronic fetal monitoring have not been investigated in Ireland. A national survey of all (n = 22) maternity units in Ireland was undertaken using a self-reported questionnaire amended, with permission, from that used in the 8th CESDI report. The questionnaire sought information on unit birth rate in 2002, number of cardiotocograph (CTG) monitors available in delivery units, use of the admission CTG, use of continuous EFM for women with various risk factors for pregnancy and/or labour, availability of fetal blood sampling facilities, use of umbilical cord blood sampling and availability of guidelines on the use of EFM. All units responded to the survey giving a national picture of the use of EFM during labour. All units had cardiotocograph (CTG) monitors available in the delivery area (median 6, range 3-14). An admission CTG was performed on all women by 96% (n=21) of units. Thirty six per cent of units (n=8) used continuous EFM routinely during labour in women who did not have risk factors for labour. Fetal blood sampling (FBS) was used in 36% (n=8) of units in cases of suspicious CTG tracings. Umbilical cord blood gases were sampled routinely following emergency caesarean section in 46% (n= 10) of units while 64% (n= 14) did so if the baby's condition was poor at birth. A departmental guideline on the use of EFM was available in 73% (n= 16) units. The findings of this survey indicate wide variations in the use of intrapartum EFM in Ireland. The use of continuous EFM for specific high-risk indications was variable and EFM was used by a third of units for women who did not have risk factors for labour. The admission CTG was used by 21 of the 22 units despite evidence of no benefit. The absence of FBS in the majority of units surveyed and the low rate of umbilical cord blood sampling is of concern.

Potential predictors of chemotherapy response in ovarian cancer--how do we define chemosensitivity?

OBJECTIVE: The aim of this study was to assess whether microvessel density (measured by CD31), vascular endothelial growth factor (VEGF) or multidrug resistance (MDR1) could determine the response to chemotherapy or act as prognostic factors in ovarian cancer. METHODS: Seventy-nine ovarian specimens were immunostained. Pearson correlation, 1-way ANOVA and chi-square were used for univariate analysis. Kaplan Meier survival curves were used, log-rank was used for univariate analysis and a Cox proportional hazards regression model was used for multivariate evaluation. Response to chemotherapy was assessed after 6 months and again after 1 year. RESULT: Quantifying VEGF proved to be a valuable independent prognostic indicator in progression-free survival (PFS) (p<0.05) and overall survival (OS) (p<0.0001). VEGF correlated with response to chemotherapy at the 6-month interval (r=0.446, p<0.001) but failed to correlate at the 1-year interval. Increased staining with CD31 was associated with decreased PFS (p<0.01) and OS (p<0.01) in univariate but not multivariate analysis. MDR1 failed to act as a prognostic marker or as a predictor of response to chemotherapy. CONCLUSION: VEGF correlates with response to chemotherapy at the 6-month but not the 12-month interval. What should our criteria be for determining sensitivity to chemotherapy? CD31, VEGF and MDR1 do play a role in some ovarian malignancies but other factors are likely to be involved and perhaps molecular profiling will determine which factors will be important for determining the response to chemotherapy.

Haemostatic risk factors in healthy postmenopausal women taking hormone replacement therapy.

OBJECTIVE: To compare changes in haemostatic parameters in healthy postmenopausal women taking either tibolone or 17beta-oestradiol/norethisterone acetate. METHODS: Factor VIIc, antithrombin, fibrinogen, thrombin-antithrombin complex (TAT), FDP (D-Dimer), tissue plasminogen activator (tPA) and plasminogen activator inhibitor I (PAI-1) were measured in 80 healthy postmenopausal women after 3, 6 and 12 months therapy with either 17beta-oestradiol/norethisterone acetate or tibolone. RESULTS: Both treatments significantly reduced fibrinogen, factor VIIc, antithrombin, tPA and PAI-1 antigen. Significantly lower levels of factor VIIc activity were observed on treatment with tibolone compared with 17beta-oestradiol/norethisterone acetate. TAT was unchanged with both treatments as was tPA activity. FDP (D-dimer) was increased on treatment with both preparations. CONCLUSIONS: The enhanced fibrin turnover and reduced antithrombin activity may play a role in the increased risk of venous thromboembolism in some susceptible women taking hormone replacement therapy (HRT) and could explain the lack of benefit of HRT in the secondary prevention of cardiovascular disease. The decreased levels of fibrinogen and factor VIIc found during treatment with 17beta-oestradiol/norethisterone acetate or tibolone may offer some degree of cardioprotection in healthy woman without pre-existing disease.

von Willebrand's disease: an important cause of dysfunctional uterine bleeding.

We assessed the prevalence of von Willebrand's disease (VWD) in patients with objectively confirmed dysfunctional uterine bleeding. A case-control study was designed to include 38 patients with objectively confirmed dysfunctional uterine bleeding and 38 age-matched controls with normal menstrual blood loss (MBL). Menorrhagia was defined as a mean MBL of greater than 80 ml on three consecutive menses as measured by the alkali haematin method. von Willebrand factor antigen, von Willebrand factor activity (VWF:Ac) and factor VIII:C were measured on three serial venous blood samples 1 week apart. VWD was diagnosed in five of 38 (13%) patients with menorrhagia and one of 38 (2.6%) patients with normal menstrual blood loss. The mean VWF:Ac value was significantly reduced in patients with menorrhagia (mean +/- standard deviation, 84.5 +/- 26.7 IU/dl versus 103.9 +/- 34.5 IU/dl; P < 0.01) and this effect persisted after exclusion of patients diagnosed with VWD. Failure to investigate patients for VWD will limit the potential benefits of medical therapies such as tranexamic acid or nasal desmopressin [1-desamino-8-D-arginine vasopressin, (DDAVP)] and, in addition, will lead to an increased risk associated with surgical intervention in patients with undiagnosed VWD.

Serous papillary adenocarcinomas of the ovary display heterogeneity in their response to chemotherapy.

The response of ovarian serous papillary adenocarcinomas to various cytotoxic drugs was examined using the (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) cytotoxicity assay. Thirty tumors were collected and organized into four groups according to histologic grade and FIGO stage: stage III, grade 2; stage III, grade 3; stage IV, grade 2; and stage IV, grade 3. The MTS chemosensitivity assay was performed on each tumor to examine the response to cisplatin, paclitaxel, hycamtin and the combination of cisplatin and paclitaxel. Ovarian adenocarcinomas of similar stage and grade displayed varying responses to the same drug. A lower concentration of the drug was often as effective as the peak plasma concentration. For some specimens combination therapy was more effective for inhibiting tumor growth, and for others single-agent therapy gave a better response. A chemosensitivity/resistance profile is recommended before deciding on appropriate chemotherapy.

Differential effects of raloxifene and continuous combined hormone replacement therapy on biochemical markers of cardiovascular risk: results from the Euralox 1 study.

OBJECTIVE: To compare the effects of the selective estrogen receptor modulator (SERM) raloxifene (Evista) and a continuous combined hormone replacement therapy (ccHRT) formulation containing estradiol and norethisterone acetate (Kliogest) on lipid and fibrinogen levels of postmenopausal women. METHODS: Euralox 1 was a prospective, randomized, double-blind trial. After a placebo wash-out, healthy postmenopausal women (n = 1008, average age 56.1 +/- 4.9 years) with a health risk profile that suggested a potential benefit from either treatment were randomly assigned to either 60 mg raloxifene or ccHRT consisting of 2 mg estradiol and 1 mg norethisterone acetate (NETA) per day for 6 months. MEASUREMENTS: Total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol with its fractions HDL2 and HDL3, the LDL/HDL ratio, triglycerides and fibrinogen were assessed at baseline and after 6 months or on early drop-out. RESULTS: Baseline values were comparable between the two groups. Blood samples of 841 women (83.4%) were available at baseline and endpoint. Total and LDL cholesterol decreased statistically significantly from baseline to endpoint in both treatment arms (by 7.2% and 3.8% with raloxifene and by 13.0% and 8.9% with ccHRT, respectively). Raloxifene produced a statistically significant increase in HDL cholesterol by 4.2%, while ccHRT induced a decline by 9.5%. Triglycerides were moderately suppressed with raloxifene and ccHRT, by 3.6 and 5.4%, respectively. Fibrinogen fell by 7.0% with raloxifene and rose by 3.6% with ccHRT. CONCLUSIONS: Continuous combined HRT was associated with decreases in total cholesterol and LDL cholesterol about twice as large as with raloxifene, but also with a decrease in HDL cholesterol. The smaller decreases in total cholesterol and LDL cholesterol associated with raloxifene were accompanied by an increase in HDL cholesterol and a decrease in fibrinogen. In conclusion, raloxifene affects fibrinogen concentrations and the overall cholesterol profile more favorably than ccHRT; these differences may have important implications for the reduction of cardiovascular disease.