Infliximab treatment efficacy in lymphoedema associated with ankylosing spondylitis

SIR, Lymphoedema is an extra-articular manifestation rarelyfound in rheumatoid arthritis (RA) and juvenile idiopathic arthritis,and is quite rare in psoriatic arthritis (PsA) [1–4].Literature research shows few published cases of lymphoedema:30 cases in patients with RA and only eight cases in PsA [5–7     

Misoprostol for induction of labour: a systematic review.

OBJECTIVE: To determine, from the best available evidence, the effectiveness and safety of misoprostol administered vaginally or orally for third trimester cervical ripening or induction of labour. METHODS: Clinical trials of misoprostol used for cervical ripening or labour induction in the third trimester were identified from the register of randomised trials maintained by the Cochrane Pregnancy and Childbirth Group. All identified trials were considered for inclusion in the review according to a prespecified protocol. Primary outcomes were chosen to address clinical effectiveness (delivery within 24 hours) and safety (uterine hyperstimulation, caesarean section, serious maternal and neonatal morbidity) and were determined a priori. All meta-analyses were based on the intention-to-treat principle. In the absence of heterogeneity the summary statistics have been expressed as typical relative risk (RR) and 95% confidence interval (CI). RESULTS: Vaginal misoprostol: one small study showed that the use of misoprostol results in more effective cervical ripening and reduced need for oxytocin when compared with placebo. When compared with oxytocin, vaginal misoprostol was more effective for labour induction. The relative risk of failure to achieve vaginal delivery within 24 hours was 0.48 (95% CI 0.35 to 0.66). However, the relative risks for uterine hyperstimulation with and without fetal heart rate abnormalities were 2.54 (95% CI 1.12 to 5.77) and 2.96 (95% CI 2.11 to 4.14), respectively. In three out of four trials which studied women with intact membranes and unfavourable cervices, failure to achieve vaginal delivery within 24 hours was reduced with misoprostol when compared with other prostaglandins (RR 0.71, 95% CI 0.62 to 0.81). Vaginal misoprostol was associated with increased uterine hyperstimulation both without fetal heart rate changes (RR 1.67, 95% CI 1.30 to 2.14) and with associated fetal heart rate changes (RR 1.45, 95% CI 1.04 to 2.04). There was also an increase in meconium stained amniotic fluid following vaginal misoprostol (RR 1.38, 95% CI 1.06 to 1.79). Oral misoprostol: one small trial suggests that, when compared with placebo, oral misoprostol reduces the need for oxytocin and shortens the time between induction and delivery. Compared with other prostaglandins one small trial showed a reduced need for oxytocin with oral misoprostol. Two trials compared oral with vaginal misoprostol using different doses. No significant differences were evident. CONCLUSIONS: Overall, misoprostol appears to be more effective than conventional methods of cervical ripening and labour induction. Although no differences in perinatal outcome were shown, the studies were not sufficiently large to exclude the possibility of uncommon serious adverse effects. In particular the increase in uterine hyperstimulation with fetal heart rate changes following misoprostol is a matter for concern. It is possible that, if sufficient numbers are studied, an unacceptably high number of serious adverse events including uterine rupture and asphyxial fetal deaths may occur. The data at present are not robust enough to address the issue of safety. Thus, though misoprostol shows promise as a highly effective, inexpensive and convenient agent for labour induction, it cannot be recommended for routine use at this stage. Lower dose misoprostol regimens should be investigated further.     

How strong is the association between maternal thrombophilia and adverse pregnancy outcome? A systematic review.

OBJECTIVE: To determine whether inherited and acquired thrombophilias are associated with adverse obstetric complications. STUDY DESIGN: A systematic review; studies where women with adverse obstetric complications were tested for one or more acquired and inherited thrombophilias were included. MAIN OUTCOME MEASURES: Prevalence of thrombophilia in women with severe pre-eclampsia/eclampsia, severe placental abruption, intrauterine growth restriction or unexplained stillbirth. RESULTS: Compared with controls, placental abruption was more often associated with homozygous and heterozygous factor V Leiden mutation, heterozygous G20210A prothrombin gene mutation, homocysteinaemia, activated protein C resistance or anticardiolipin IgG antibodies. Women with pre-eclampsia/eclampsia were more likely to have heterozygous factor V Leiden mutation, heterozygous G20210A prothrombin gene mutation, homozygous MTHFR C677T mutation, protein C deficiency, protein S deficiency or activated protein C resistance compared with controls. Unexplained stillbirth, when compared with controls, was more often associated with heterozygous factor V Leiden mutation, protein S deficiency, activated protein C resistance, anticardiolipin IgG antibodies or lupus anticoagulant. Women with intrauterine growth restriction had a higher prevalence of heterozygous G20210A prothrombin gene mutation, homozygous MTHFR C677T gene mutation, protein S deficiency or anticardiolipin IgG antibodies than controls. There was wide heterogeneity in the prevalence of thrombophilia between the studies. CONCLUSIONS: Women with adverse pregnancy outcome are more likely to have a positive thrombophilia screen but studies published so far are too small to adequately assess the true size of this association. Screening for thrombophilia should not become standard practice until clear evidence emerges that thromboprophylaxis during pregnancy improves perinatal outcome. Further research into the link between the observed association, causality and heterogeneity is required.     

The impact of delivery suite guidelines on intrapartum care in 'standard primigravida'

OBJECTIVE: To compare intrapartum interventions and outcomes in low-risk primiparous women and identify factors which may contribute to the variations between different maternity units. DESIGN: Prospective observational study. PARTICIPANTS: Ten maternity units in England. METHODS: Participating units provided data on 11 clinical indicators for all 'standard primigravidae' delivered between January and December 2000 and provided information on written delivery suite policies operational during July 2000. RESULTS: There was a significant inter-unit variation in the use of intrapartum foetal blood sampling, use of syntocinon for augmentation of labour, mode of delivery, type of perineal damage, postpartum haemorrhage, low Apgar score and admission to SCBU. Units with guidelines for intrapartum foetal heart monitoring had higher rate of normal vaginal deliveries (odds ratio (OR): 1.34; 99% confidence interval (CI): 1.05-1.70) and lower rate of Caesarean section for foetal distress (OR: 0.57; 99% CI: 0.34-0.96). Units with partogram guidelines also had lower rates of Caesarean section for foetal distress (OR: 0.49; 99% CI: 0.30-0.81). Units with guidelines on the management of episiotomy had higher episiotomy rates (OR: 1.54; 99% CI: 1.15-2.06) while units with guidelines on the involvement of neonatal staff recorded less babies with Apgar score <7 at 5 min (OR: 0.37; 99% CI: 0.17-0.76). CONCLUSIONS: Written delivery suite guidelines have significant impact on the type of intrapartum care and outcome of pregnancy in low-risk women. Their availability suggests more active role of interested clinicians in the provision of intrapartum care. There is an urgent need to identify other factors that influence quality and quantity of clinical input into the care of low-risk pregnant women.     

Thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy

We investigated changes in both thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels and its functional effect on in vitro fibrinolysis in normal pregnancy. 152 pregnant women and 31 women in the immediate postpartum period were studied, with pregnancy divided into 6 windows at 4 weekly intervals. As TAFI influences and is in turn influenced by components of the protein C (PC) pathway, its measurements were correlated with levels of soluble thrombomodulin, PC, protein S (PS) and the overall phenotype of activated PC resistance (APCR). Compared with mean TAFI levels at booking gestation (6.6 +/- 1.2 microg/ml), levels peaked at 35-39 weeks gestation (9.6 +/- 2 microg/ml, p = 0.001), followed by a significant drop within 24 hours of delivery (7.2 +/- 1.1 microg/ml). In functional terms, the mean clot lysis time (CLT) (101 +/- 13 min at booking) also peaked at 35-39 weeks gestation (141 +/- 42 min, p = 0.007) and dropped after delivery (99 +/- 33 min), and was significantly correlated with gestational age (r = 0.410, p = 0.001) and could be abrogated in the presence of an inhibitor to TAFI activation. A significant negative correlation was found between TAFI levels and APCR (r = -0.478, p <0.001), APCRV (r = -0.598; p <0.001), PS (r = -0.490, P <0.001) and PC (r = -0.198, p = 0.02). In summary, there is a significant increase in TAFI levels, which translates into increased CLT during pregnancy. Furthermore, changes in TAFI contribute to the increasing APCR of pregnancy.