Seizures are the main cause of maternal death in women with epilepsy, but there are no tools for predicting seizures in pregnancy. We set out to develop and validate a prognostic model, using ...information collected during the antenatal booking visit, to predict seizure risk at any time in pregnancy and until 6 weeks postpartum in women with epilepsy on antiepileptic drugs.
We used datasets of a prospective cohort study (EMPiRE) of 527 pregnant women with epilepsy on medication recruited from 50 hospitals in the UK (4 November 2011-17 August 2014). The model development cohort comprised 399 women whose antiepileptic drug doses were adjusted based on clinical features only; the validation cohort comprised 128 women whose drug dose adjustments were informed by serum drug levels. The outcome was epileptic (non-eclamptic) seizure captured using diary records. We fitted the model using LASSO (least absolute shrinkage and selection operator) regression, and reported the performance using C-statistic (scale 0-1, values > 0.5 show discrimination) and calibration slope (scale 0-1, values near 1 show accuracy) with 95% confidence intervals (CIs). We determined the net benefit (a weighted sum of true positive and false positive classifications) of using the model, with various probability thresholds, to aid clinicians in making individualised decisions regarding, for example, referral to tertiary care, frequency and intensity of monitoring, and changes in antiepileptic medication. Seizures occurred in 183 women (46%, 183/399) in the model development cohort and in 57 women (45%, 57/128) in the validation cohort. The model included age at first seizure, baseline seizure classification, history of mental health disorder or learning difficulty, occurrence of tonic-clonic and non-tonic-clonic seizures in the 3 months before pregnancy, previous admission to hospital for seizures during pregnancy, and baseline dose of lamotrigine and levetiracetam. The C-statistic was 0.79 (95% CI 0.75, 0.84). On external validation, the model showed good performance (C-statistic 0.76, 95% CI 0.66, 0.85; calibration slope 0.93, 95% CI 0.44, 1.41) but with imprecise estimates. The EMPiRE model showed the highest net proportional benefit for predicted probability thresholds between 12% and 99%. Limitations of this study include the varied gestational ages of women at recruitment, retrospective patient recall of seizure history, potential variations in seizure classification, the small number of events in the validation cohort, and the clinical utility restricted to decision-making thresholds above 12%. The model findings may not be generalisable to low- and middle-income countries, or when information on all predictors is not available.
The EMPiRE model showed good performance in predicting the risk of seizures in pregnant women with epilepsy who are prescribed antiepileptic drugs. Integration of the tool within the antenatal booking visit, deployed as a simple nomogram, can help to optimise care in women with epilepsy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Raised blood pressure (BP) affects approximately 10% of pregnancies worldwide, and a high proportion of affected women develop pre-eclampsia. This study aimed to evaluate the feasibility of ...self-monitoring of BP in pregnancy in women at higher risk of pre-eclampsia.
This prospective cohort study of self-monitoring BP in pregnancy was carried out in two hospital trusts in Birmingham and Oxford and thirteen primary care practices in Oxfordshire. Eligible women were those defined by the UK National Institute for Health and Care Excellence (NICE) guidelines as at higher risk of pre-eclampsia. A total of 201 participants were recruited between 12 and 16 weeks of pregnancy and were asked to take two BP readings twice daily three times a week through their pregnancy. Primary outcomes were recruitment, retention and persistence of self-monitoring. Study recruitment and retention were analysed with descriptive statistics. Survival analysis was used to evaluate the persistence of self-monitoring and the performance of self-monitoring in the early detection of gestational hypertension, compared to clinic BP monitoring. Secondary outcomes were the mean clinic and self-monitored BP readings and the performance of self-monitoring in the detection of gestational hypertension and pre-eclampsia compared to clinic BP.
Of 201 women recruited, 161 (80%) remained in the study at 36 weeks or to the end of their pregnancy, 162 (81%) provided any home readings suitable for analysis, 148 (74%) continued to self-monitor at 20 weeks and 107 (66%) at 36 weeks. Self-monitored readings were similar in value to contemporaneous matched clinic readings for both systolic and diastolic BP. Of the 23 who developed gestational hypertension or pre-eclampsia and self-monitored, 9 (39%) had a raised home BP prior to a raised clinic BP.
Self-monitoring of BP in pregnancy is feasible and has potential to be useful in the early detection of gestational hypertensive disorders but maintaining self-monitoring throughout pregnancy requires support and probably enhanced training.
Pregnant women with epilepsy on antiepileptic drugs (AEDs) may experience a reduction in serum AED levels. This has the potential to worsen seizure control.
To determine if, in pregnant women with ...epilepsy on AEDs, additional therapeutic drug monitoring reduces seizure deterioration compared with clinical features monitoring after a reduction in serum AED levels.
A double-blind, randomised trial nested within a cohort study was conducted and a qualitative study of acceptability of the two strategies was undertaken. Stratified block randomisation with a 1 : 1 allocation method was carried out.
Fifty obstetric and epilepsy clinics in secondary and tertiary care units in the UK.
Pregnant women with epilepsy on one or more of the following AEDs: lamotrigine, carbamazepine, phenytoin or levetiracetam. Women with a ≥ 25% decrease in serum AED level from baseline were randomised to therapeutic drug monitoring or clinical features monitoring strategies.
In the therapeutic drug monitoring group, clinicians had access to clinical findings and monthly serum AED levels to guide AED dosage adjustment for seizure control. In the clinical features monitoring group, AED dosage adjustment was based only on clinical features.
Primary outcome - seizure deterioration, defined as time to first seizure and to all seizures after randomisation per woman until 6 weeks post partum. Secondary outcomes - pregnancy complications in mother and offspring, maternal quality of life, seizure rates in cohorts with stable serum AED level, AED dose exposure and adverse events related to AEDs.
Analysis of time to first and to all seizures after randomisation was performed using a Cox proportional hazards model, and multivariate failure time analysis by the Andersen-Gill model. The effects were reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Secondary outcomes were reported as mean differences (MDs) or odds ratios.
A total of 130 women were randomised to the therapeutic drug monitoring group and 133 to the clinical features monitoring group; 294 women did not have a reduction in serum AED level. A total of 127 women in the therapeutic drug monitoring group and 130 women in the clinical features monitoring group (98% of complete data) were included in the primary analysis. There were no significant differences in the time to first seizure (HR 0.82, 95% CI 0.55 to 1.2) or timing of all seizures after randomisation (HR 1.3, 95% CI 0.7 to 2.5) between both trial groups. In comparison with the group with stable serum AED levels, there were no significant increases in seizures in the clinical features monitoring (odds ratio 0.93, 95% CI 0.56 to 1.5) or therapeutic drug monitoring group (odds ratio 0.93, 95% CI 0.56 to 1.5) associated with a reduction in serum AED levels. Maternal and neonatal outcomes were similar in both groups, except for higher cord blood levels of lamotrigine (MD 0.55 mg/l, 95% CI 0.11 to 1 mg/l) or levetiracetam (MD 7.8 mg/l, 95% CI 0.86 to 14.8 mg/l) in the therapeutic drug monitoring group than in the clinical features monitoring group. There were no differences between the groups on daily AED exposure or quality of life. An increase in exposure to lamotrigine, levetiracetam and carbamazepine significantly increased the cord blood levels of the AEDs, but not maternal or fetal complications. Women with epilepsy perceived the need for weighing up their increased vulnerability to seizures during pregnancy against the side effects of AEDs.
Fewer women than the original target were recruited.
There is no evidence to suggest that regular monitoring of serum AED levels in pregnancy improves seizure control or affects maternal or fetal outcomes.
Further evaluation of the risks of seizure deterioration for various threshold levels of reduction in AEDs and the long-term neurodevelopment of infants born to mothers in both randomised groups is needed. An individualised prediction model will help to identify those women who need close monitoring in pregnancy.
Current Controlled Trials ISRCTN01253916.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 22, No. 23. See the NIHR Journals Library website for further project information.
The use of Kielland's forceps has declined significantly in the last three decades. There is a lack of quality evidence on potential benefits and harms associated with using these forceps. We have ...performed a systematic review of the literature and meta-analysis to assess the safety and efficacy of using Kielland's forceps.
We have searched electronic databases for all clinical studies reporting primary data on using Kielland's forceps and assessed their risk of bias using the Newcastle-Ottawa Scale. We have pooled the event rate of adverse outcomes reported following the use of Kielland's forceps including a direct comparison to rotational ventouse. In total we included 23 studies. Direct comparison meta-analysis revealed higher failure rate with rotational ventouse compared with Kielland's. There was no statistically significant difference in the risk of adverse maternal outcomes between the two groups. There was higher risk of neonatal trauma in the ventouse group, but no significant difference in other neonatal outcomes.
Kielland's forceps have a high success rate with relatively low adverse outcomes despite their use being controversial. In comparison to rotational ventouse, Kielland's forceps have higher efficacy with less risk of neonatal trauma.
Abstract Objectives Pregnant women with epilepsy have a significantly increased risk of mortality and morbidity compared to non-pregnant women. At least one in 250 pregnancies is exposed to ...anti-epileptic drugs (AED). Seizure deterioration occurs in up to a third of pregnant women. AED levels fall in most pregnant women, although it is uncertain that this is responsible for seizure deterioration rather than a hormonal effect. Current practice of AED monitoring is either therapeutic drug monitoring (TDM) or clinical features monitoring (CFM) to adjust the AED dose. We have systematically reviewed the effectiveness of the two monitoring regimens for AEDs, especially lamotrigine, the most commonly used AED in pregnancy on maternal and fetal outcomes. Study design We searched MEDLINE (1966–2012), EMBASE (1980–2012) and Cochrane, for relevant citations on the effectiveness of different monitoring strategies on seizure deterioration in pregnant women with epilepsy on lamotrigine. Study selection, quality assessment and data extraction were carried out by two independent reviewers. We calculated the rates of deterioration in seizures with the two strategies and pooled the estimates with random effects meta-analysis. Results Six observational studies ( n = 132) evaluated the effectiveness of the two monitoring strategies on pregnant women with epilepsy on lamotrigine. There were no randomised controlled trials. The rate of seizure deterioration was 0.30 (95% CI 0.21–0.41) in women monitored by therapeutic drug monitoring (TDM) compared to 0.73 (95% CI 0.56–0.86) in those receiving clinical feature monitoring (CFM) alone. Conclusion Evidence based on observational data suggests that monitoring of AED levels in pregnancy reduces seizure deterioration, although the included studies have numerous sources of bias. There is paucity of evidence to make firm recommendations on optimal monitoring of AED drugs in pregnancy. Further research is needed to advise on the best clinical practice in managing AED in pregnancy.
Abstract Studies on pregnant women with epilepsy should evaluate both neurological and pregnancy outcomes. We undertook a systematic review of the literature of studies on pregnant women with ...epilepsy to collate the outcomes reported, and the quality of outcomes report in these studies. We searched major electronic databases (from 1999 until January 2015). Two independent reviewers selected studies and extracted data on study design, the risk of bias of the studies, journal impact factor and the quality of reported outcomes. We assessed the quality outcomes report using a six items standardised tool (score range 0–6). There were 70 different outcomes reported in 232 studies (maternal neurological (13/70, 19%), fetal and neonatal (28/70, 40%), and obstetric outcomes (29/70, 41%)). Most studies reported on major congenital fetal abnormalities (103/232, 44%), followed by live birth (60/232, 26%). Quality of the reported outcomes was poor (mean 1.54, SD 1.36). It was associated with journal impact factor ( p = 0.007), but not with study design ( p = 0.60), or risk of bias ( p = 0.17). The outcomes reported in studies on pregnant women with epilepsy varied widely, and the quality of the outcomes report was poor. There is a need to identify a set of core outcome to harmonise reporting in future clinical studies.
During the last five years, I have had under my sole charge in private practice the care of ten cases of Haemorrhage into the Internal Capsule. I have made a practical study of these cases, by ...writing graphic methods and by photography . These notes and records form the basis of this thesis. I shall endeavour to make it as practical as possible and shall therefore give an account of these ten cases and then state my own observations regarding the etiology, pathology, prognosis, and treatment of these ten cases. A most important question after cerebral haemorrhage is "will the patient be able to walk again, and if so to what extent?" I have made this subject of AFTER GAIT a special study. I shall show by photographic records the characteristic gait that comes on after a cerebral haemorrhage into the Internal capsule. I shall describe the first case - that of A.P. more fully than the others as it is a very typical case and serves well to illustrate the symptoms of cerebral haemorrhage into the internal capsule .The after gait in each case has been recorded in which the patient was sufficiently able to walk, to make an intelligent record.
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