ORCID Profile
0000-0001-7904-7933
Current Organisation
King's College London
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Publisher: Cambridge University Press (CUP)
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 18-02-2014
Publisher: Springer Science and Business Media LLC
Date: 15-07-2013
Publisher: Oxford University Press (OUP)
Date: 10-2000
DOI: 10.1016/S1010-7940(00)00535-2
Abstract: Positron emission tomography (PET) is being increasingly used as an accurate and non-invasive modality in diagnosis, staging and post-therapy assessment in patients with lung cancer. In this study, we examine whether the uptake of [(18)F]fluorodeoxyglucose (FDG), a marker of increased glucose metabolism in neoplastic cells, is of prognostic value in patients with primary lung cancer. We have retrospectively analyzed 77 patients (mean age, 63. 0 years male/female ratio, 53:24) with primary lung cancers who underwent whole body and localized thoracic PET as part of their diagnostic and staging procedures prior to consideration of surgical resection. The standardized uptake value (SUV) of injected FDG for each primary lesion was correlated with tumour histology and the patient's clinical outcome. A SUV of 20 or greater was found to be of significant prognostic value. The chance of survival (with 95% confidence intervals (CI)) at 12 months post-surgery for the various SUV groups was as follows: 75.2% (59.6-85.5) for SUV<10 67.5% (29.0-88.2) for SUV 10-<12 63.6% (29.7-84.5) for SUV 12-<15 66.7% (19.5-90.4) for SUV 15- 20. A SUV of 20 or more is associated with a 4.66 times increase in hazard, compared with lower levels of SUV. We found no significant correlation between tumour histology and SUV. We have previously reported on the significant advantages of PET in the staging and surgical care of patients with lung cancer. The present study adds further support for an additional prognostic role for PET in the management of thoracic malignancy as determined by the amount of labelled-FDG taken up by the primary lesion.
Publisher: Wiley
Date: 23-04-2009
DOI: 10.1111/J.1471-0528.2009.02137.X
Abstract: To assess the accuracy of fetal fibronectin (fFN) testing for prediction of preterm labour in asymptomatic high-risk women with a cervical cerclage. Retrospective observational study. United Kingdom. Nine hundred and ten asymptomatic women at high-risk of Preterm birth referred to specialist antenatal clinics and undergoing fFN testing between November 1997 and December 2007. Women had fFN tests taken between 23(+0) and 27(+6) weeks' gestation, on one or more occasions. Sensitivity, specificity, positive predictive values and negative predictive values of fFN testing for predicting delivery <30 and <37 weeks were compared in those with and without cerclage. For delivery <30 weeks' gestation, the specificity of fFN testing was significantly lower in women with cervical cerclage (77% vs 90% P 0.4). The negative predictive value of the fFN test for delivery 98%). Asymptomatic high-risk women with cerclage in situ are more likely to have a false positive fFN test. The negative predictive value is similar.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
DOI: 10.1161/HYPERTENSIONAHA.121.17171
Abstract: This study evaluated whether planned early delivery would ameliorate cardiovascular dysfunction 6 months postpartum, compared with usual care with expectant management, in women with late preterm preecl sia. We conducted a mechanistic observational study in women with preterm preecl sia between 34 +0 and 36 +6 weeks’ gestation, nested within a randomized controlled trial of planned early delivery versus expectant management (usual care), in 28 maternity hospitals in England and Wales. Women were followed up 6 months postpartum with cardiovascular assessments. The primary outcome was a composite of systolic and diastolic dysfunction (by 2009 and 2016 definitions of diastolic dysfunction). Between April 27, 2016, and November 30, 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited. One hundred thirty-three women were randomized to planned delivery, 137 women were randomized to expectant management within the trial, while 150 women received expectant management outside of the trial. 321 (76.4%) completed their 6 month echocardiography assessment. 10% (31/321) had a left ventricular ejection fraction % while 71% (229/321) remained hypertensive. There were no differences in the primary outcome between the 2 randomized groups (planned delivery versus expectant management) using either the 2009 (risk ratio, 1.06 [95% CI, 0.80–1.40]) or 2016 definitions (risk ratio, 0.78 [0.33–1.86]). In conclusion, we demonstrated that late preterm preecl sia results in persistence of hypertension in the majority and systolic LV dysfunction in 10%, of women 6 months postpartum. Planned early delivery does not affect these outcomes. Preecl sia is not a self-limiting disease of pregnancy alone.
Publisher: Informa UK Limited
Date: 19-06-2019
DOI: 10.1080/01443615.2019.1593333
Abstract: An impaction of the foetal head at caesarean section is a topical concern in modern obstetric practice. The management options for this problem are well described but the incidence or even definition of impaction, is unknown. The primary aim of this study was to ascertain the incidence of impacted foetal head at CS in labour. This prospective study used data from all women undergoing CS during a 12-month period in a single unit. Following completion of all CS, the surgeon completed a questionnaire covering: cervical dilation at time of CS if the surgeon felt there was a difficulty in delivering the foetal head as an indicator of impaction, as well as the other techniques utilised. Of 440 EMCS in labour, 18% (
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2019
Publisher: Wiley
Date: 05-12-2005
DOI: 10.1111/J.1471-0528.2005.00788.X
Abstract: To determine whether metronidazole reduces early preterm labour in asymptomatic women with positive vaginal fetal fibronectin (fFN) in the second trimester of pregnancy. Randomised placebo-controlled trial. Fourteen UK hospitals (three teaching). Pregnancies with at least one previous risk factor, including mid-trimester loss or preterm delivery, uterine abnormality, cervical surgery or cerclage. Nine hundred pregnancies were screened for fFN at 24 and 27 weeks of gestation. Positive cases were randomised to a week's course of oral metronidazole or placebo. Primary outcome was delivery before 30 weeks of gestation. Secondary outcomes included delivery before 37 weeks. The Trial Steering Committee (TSC) recommended the study be stopped early 21% of women receiving metronidazole (11/53) delivered before 30 weeks compared with 11% (5/46) taking placebo [risk ratio 1.9, 95% confidence interval (CI) 0.72-5.09, P = 0.18]. There were significantly more preterm deliveries (before 37 weeks) in women treated with metronidazole 33/53 (62%) versus placebo 18/46 (39%), risk ratio 1.6, 95% CI 1.05-2.4. fFN was a good predictor of early preterm birth in these asymptomatic women positive and negative predictive values (24 weeks of gestation) for delivery by 30 weeks were 26% and 99%, respectively (positive and negative likelihood ratios 15, 0.35). Metronidazole does not reduce early preterm birth in high risk pregnant women selected by history and a positive vaginal fFN test. Preterm delivery may be increased by metronidazole therapy.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2015
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.AJOG.2016.04.041
Abstract: Congophilia indicates the presence of amyloid protein, which is an aggregate of misfolded proteins, that is implicated in the pathophysiologic condition of preecl sia. Recently, urinary congophilia has been proposed as a test for the diagnosis and prediction of preecl sia. The purpose of this study was to determine whether urine congophilia is present in a cohort of women with preecl sia and in pregnant and nonpregnant women with renal disease. With the use of a preecl sia, chronic hypertension, renal disease, and systemic lupus erythematosus cohort, we analyzed urine s les from healthy pregnant control subjects (n = 31) and pregnant women with preecl sia (n = 23), gestational hypertension (n = 10), chronic hypertension (n = 14), chronic kidney disease n = 28), chronic kidney disease with superimposed preecl sia (n = 5), and chronic hypertension and superimposed preecl sia (n = 12). S les from nonpregnant control subjects (n = 10) and nonpregnant women with either systemic lupus erythematosus with (n = 25) and without (n = 14) lupus nephritis were analyzed. For each s le, protein concentration was standardized before it was mixed with Congo Red, spotted to nitrocellulose membrane, and rinsed with methanol. The optical density of the residual Congo Red stain was determined Congo red stain retention was calculated, and groups were compared with the use of the Mann-Whitney test or Kruskal-Wallis analysis of Variance test, as appropriate. Congophilia was increased in urine from women with preecl sia (median Congo red stain retention, 47% interquartile range, 22-68%) compared with healthy pregnant control subjects (Congo red stain retention: 16% interquartile range, 13-21% P = .002), women with gestational hypertension (Congo red stain retention, 20% interquartile range, 13-27% P = .008), or women with chronic hypertension (Congo red stain retention, 17% interquartile range, 12-28% P = .01). There were no differences in Congo red retention between pregnant women with chronic hypertension and normal pregnant control subjects (Congo red stain retention, 17% [interquartile range, 12-28%] vs 16% [interquartile range, 13-21%], respectively P = .72). Congophilia was present in pregnant women with chronic kidney disease (Congo red stain retention, 32% interquartile range, 14-57%), being similar to values found in women with preecl sia (P = .22) and for women with chronic kidney disease and superimposed preecl sia (Congo red stain retention, 57% [interquartile range, 29-71% P = .18). Nonpregnant women with lupus nephritis had higher congophilia levels compared with nonpregnant female control subjects (Congo red stain retention, 38% [interquartile range, 17-73%] vs 9% [7-11%], respectively P < .001) and nonpregnant women with systemic lupus erythematosus without nephritis (Congo red stain retention, 38% [interquartile range, 17-73%] vs 13% [interquartile range, 11-17%], respectively P = .001). A significant positive correlation was observed between congophilia and protein:creatinine ratio (Spearman rank correlations, 0.702 95% confidence interval, 0.618-0.770 P < .001). This study confirms that women with preecl sia and chronic kidney disease without preecl sia have elevated urine congophilia levels compared with healthy pregnant women. Nonpregnant women with lupus nephritis also have elevated urine congophilia levels compared with healthy control subjects. An elevated Congo Red stain retention may not be able to differentiate between these conditions further research is required to explore the use of congophilia in clinical practice.
Publisher: Wiley
Date: 12-02-2014
Publisher: Wiley
Date: 17-07-2019
Publisher: Elsevier BV
Date: 09-1999
Publisher: Royal College of General Practitioners
Date: 04-2013
Publisher: Cambridge University Press (CUP)
Date: 2013
Publisher: MDPI AG
Date: 09-06-2021
DOI: 10.3390/NU13061979
Abstract: Pregnancy can alter a woman’s weight gain trajectory across the life course and contribute to the development of obesity through retention of weight gained during pregnancy. This study aimed to identify modifiable determinants associated with postpartum weight retention (PPWR calculated by the difference in pre-pregnancy and 6 month postpartum weight) in 667 women with obesity from the UPBEAT study. We examined the relationship between PPWR and reported glycaemic load, energy intake, and smoking status in pregnancy, excessive gestational weight gain (GWG), mode of delivery, self-reported postpartum physical activity (low, moderate, and high), and mode of infant feeding (breast, formula, and mixed). At the 6 month visit, 48% (n = 320) of women were at or above pre-pregnancy weight. Overall, PPWR was negative (−0.06 kg (−42.0, 40.4)). Breastfeeding for ≥4 months, moderate or high levels of physical activity, and GWG ≤9 kg were associated with negative PPWR. These three determinants were combined to provide a modifiable factor score (range 0–3) for each added variable, a further reduction in PPWR of 3.0 kg (95% confidence interval 3.76, 2.25) occurred compared to women with no modifiable factors. This study identified three additive determinants of PPWR loss. These provide modifiable targets during pregnancy and the postnatal period to enable women with obesity to return to their pre-pregnancy weight.
Publisher: Wiley
Date: 27-12-2019
DOI: 10.1111/IJPO.12608
Publisher: Springer Science and Business Media LLC
Date: 12-10-2022
DOI: 10.1038/S41366-022-01210-3
Abstract: Obesity in pregnancy has been associated with increased childhood cardiometabolic risk and reduced life expectancy. The UK UPBEAT multicentre randomised control trial was a lifestyle intervention of diet and physical activity in pregnant women with obesity. We hypothesised that the 3-year-old children of women with obesity would have heightened cardiovascular risk compared to children of normal BMI women, and that the UPBEAT intervention would mitigate this risk. Children were recruited from one UPBEAT trial centre. Cardiovascular measures included blood pressure, echocardiographic assessment of cardiac function and dimensions, carotid intima-media thickness and heart rate variability (HRV) by electrocardiogram. Compared to offspring of normal BMI women ( n = 51), children of women with obesity from the trial standard care arm ( n = 39) had evidence of cardiac remodelling including increased interventricular septum (IVS mean difference 0.04 cm 95% CI: 0.018 to 0.067), posterior wall (PW 0.03 cm 0.006 to 0.062) and relative wall thicknesses (RWT 0.03 cm 0.01 to 0.05) following adjustment. Randomisation of women with obesity to the intervention arm ( n = 31) prevented this cardiac remodelling (intervention effect mean difference IVS −0.03 cm (−0.05 to −0.008) PW −0.03 cm (−0.05 to −0.01) RWT −0.02 cm (−0.04 to −0.005)). Children of women with obesity (standard care arm) compared to women of normal BMI also had elevated minimum heart rate (7 bpm 1.41 to 13.34) evidence of early diastolic dysfunction (e prime) and increased sympathetic nerve activity index by HRV analysis. Maternal obesity was associated with left ventricular concentric remodelling in 3-year-old offspring. Absence of remodelling following the maternal intervention infers in utero origins of cardiac remodelling. The UPBEAT trial is registered with Current Controlled Trials, ISRCTN89971375.
Publisher: Wiley
Date: 12-12-2008
DOI: 10.1111/J.1471-0528.2008.01828.X
Abstract: This study investigated the reliability, sensitivity and specificity of a commercially available absorbent pad, AmnioSense, compared with speculum examination for detection of spontaneous ruptured membranes (SRM). Prospective cohort study. Antenatal Day Unit (ADU) of a UK inner-city teaching hospital. Women attending the ADU with a history of suspected ruptured membranes between 18 and 42 weeks of gestation. Eligible women were asked to use the absorbent pad in accordance with the manufacturer's instructions. A midwife recorded the result. A second midwife performed a speculum examination according to unit protocol. Results were entered onto a password-protected study-specific database. Both midwives were blind to the other test result. Comparability between the index test (AmnioSense) and reference standard (speculum). A total of 157 women were recruited and results were analysed in 139 cases. Median gestational age at recruitment was 37(+2) weeks. The prevalence of SRM was 42% (59/139) with AmnioSense giving a sensitivity of 98% (58/59) and specificity of 65% (52/80). Thirty-eight percent (53/139 women) with SRM would have been correctly identified as having intact membranes without the need for a speculum examination. Twenty-five percent of AmnioSense false-positive results were associated with positive high vaginal swab results (7/28). These data suggest that a negative AmnioSense result can provide reassurance of intact membranes. Use of the AmnioSense test before considering speculum examination could reduce the number of speculum examinations undertaken, with benefit to women and concomitant health resource savings.
Publisher: Elsevier BV
Date: 2021
Publisher: Wiley
Date: 24-05-2014
DOI: 10.1111/DME.12482
Abstract: To examine the prediction of gestational diabetes in obese women using routine clinical measures and measurement of biomarkers related to insulin resistance in the early second trimester. A total of 117 obese pregnant women participating in a pilot trial of a complex intervention of dietary advice and physical activity were studied. Blood s les were obtained at recruitment (15⁺⁰-17⁺⁶ weeks' gestation) and demographic, clinical history and anthropometric measures recorded. The biomarkers analysed were plasma lipids (HDL cholesterol, LDL cholesterol, triglycerides), high-sensitivity C-reactive protein, alanine transaminase, aspartate transaminase, ferritin, fructosamine, insulin, adiponectin, tissue plasminogen activator, interleukin-6, visfatin and leptin. Univariate and logistic regression analyses were performed to determine independent predictors and area under the receiver-operating curve was calculated for the model. Of the 106 participants included in the analysis, 29 (27.4%) developed gestational diabetes. Participants with gestational diabetes were older (P = 0.002), more often of parity ≥ 2, had higher systolic (P = 0.02) and diastolic blood pressure (P = 0.02) and were more likely to be black (P = 0.009). Amongst the blood biomarkers measured, plasma adiponectin alone remained independently associated with gestational diabetes in adjusted models (P = 0.002). The area under the receiver-operating curve for clinical factors alone (0.760) increased significantly (area under the curve 0.834, chi-square statistic (1) = 4.00, P = 0.046) with the addition of adiponectin. A combination of routinely measured clinical factors and adiponectin measured in the early second trimester in obese women may provide a useful approach to the prediction of gestational diabetes. Validation in a large prospective study is required to determine the usefulness of this algorithm in clinical practice.
Publisher: Springer Science and Business Media LLC
Date: 14-05-2019
Publisher: Wiley
Date: 08-04-2010
DOI: 10.1111/J.1471-0528.2010.02507.X
Abstract: To evaluate the clinical and geographical variation in the use of aspirin in women at high risk of pre-ecl sia, and in the use of antihypertensive drugs and magnesium sulphate in women with established pre-ecl sia. Analysis of vitamins in pre-ecl sia (VIP) trial database. A total of 2399 women at increased risk of pre-ecl sia in 25 UK hospitals. An analysis of a large prospectively validated database of high-risk women in the UK was undertaken to assess aspirin use across different risk groups and to evaluate the use of antihypertensives and magnesium sulphate in 370 women who developed pre-ecl sia. Logistic regression was employed to compare drug use between region and by recognised clinical indicators. Usage of aspirin, antihypertensive drugs and magnesium sulphate. Of the women with known risk factors at trial entry, 24% (569/2399) received low-dose aspirin. Aspirin usage varied widely between risk groups [from 5% (19/378) in women with multiple pregnancy to 94% (50/53) in women with antiphospholipid syndrome] and between geographical regions [from 8% (20/248) to 49% (95/193)]. Three hundred and seventy women developed pre-ecl sia, 52% (n = 193) of whom received new or additional antihypertensives after 20 weeks of gestation 34% (77/224) with a maximum recorded systolic blood pressure of >OR=160 mmHg in the second half of pregnancy did not receive antihypertensive treatment 17% (62/370) of women with pre-ecl sia received magnesium sulphate prophylactically. Prophylactic and treatment regimes for pre-ecl sia in the UK vary by region and risk group.
Publisher: Public Library of Science (PLoS)
Date: 06-10-2020
Publisher: Springer Science and Business Media LLC
Date: 08-2017
Publisher: Springer Science and Business Media LLC
Date: 02-11-2020
DOI: 10.1186/S12916-020-01766-9
Abstract: Pre-ecl sia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk during pregnancy is required to plan management. Although there are many published prediction models for pre-ecl sia, few have been validated in external data. Our objective was to externally validate published prediction models for pre-ecl sia using in idual participant data (IPD) from UK studies, to evaluate whether any of the models can accurately predict the condition when used within the UK healthcare setting. IPD from 11 UK cohort studies (217,415 pregnant women) within the International Prediction of Pregnancy Complications (IPPIC) pre-ecl sia network contributed to external validation of published prediction models, identified by systematic review. Cohorts that measured all predictor variables in at least one of the identified models and reported pre-ecl sia as an outcome were included for validation. We reported the model predictive performance as discrimination ( C -statistic), calibration (calibration plots, calibration slope, calibration-in-the-large), and net benefit. Performance measures were estimated separately in each available study and then, where possible, combined across studies in a random-effects meta-analysis. Of 131 published models, 67 provided the full model equation and 24 could be validated in 11 UK cohorts. Most of the models showed modest discrimination with summary C -statistics between 0.6 and 0.7. The calibration of the predicted compared to observed risk was generally poor for most models with observed calibration slopes less than 1, indicating that predictions were generally too extreme, although confidence intervals were wide. There was large between-study heterogeneity in each model’s calibration-in-the-large, suggesting poor calibration of the predicted overall risk across populations. In a subset of models, the net benefit of using the models to inform clinical decisions appeared small and limited to probability thresholds between 5 and 7%. The evaluated models had modest predictive performance, with key limitations such as poor calibration (likely due to overfitting in the original development datasets), substantial heterogeneity, and small net benefit across settings. The evidence to support the use of these prediction models for pre-ecl sia in clinical decision-making is limited. Any models that we could not validate should be examined in terms of their predictive performance, net benefit, and heterogeneity across multiple UK settings before consideration for use in practice. PROSPERO ID: CRD42015029349 .
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.PREGHY.2018.01.004
Abstract: The fullPIERS model is a risk prediction model developed to predict adverse maternal outcomes within 48 h for women admitted with pre-ecl sia. External validation of the model is required before implementation for clinical use. We assessed the temporal and external validity of the fullPIERS model in high income settings using five cohorts collected between 2003 and 2016, from tertiary hospitals in Canada, the United States of America, Finland and the United Kingdom. The cohorts were grouped into three datasets for assessing the primary external, and temporal validity, and broader transportability of the model. The predicted risks of developing an adverse maternal outcome were calculated using the model equation and model performance was evaluated based on discrimination, calibration, and stratification. Our study included a total of 2429 women, with an adverse maternal outcome rate of 6.7%, 6.6%, and 7.0% in the primary external, temporal, and combined (broader) validation cohorts, respectively. The model had good discrimination in all datasets: 0.81 (95%CI 0.75-0.86), 0.82 (95%CI 0.76-0.87), and 0.75 (95%CI 0.71-0.80) for the primary external, temporal, and broader validation datasets, respectively. Calibration was best for the temporal cohort but poor in the broader validation dataset. The likelihood ratios estimated to rule in adverse maternal outcomes were high at a cut-off of ≥30% in all datasets. The fullPIERS model is temporally and externally valid and will be useful in the management of women with pre-ecl sia in high income settings although model recalibration is required to improve performance, specifically in the broader healthcare settings.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-12-2015
DOI: 10.1002/HEP.28265
Abstract: A challenge in obstetrics is to distinguish pathological symptoms from those associated with normal changes of pregnancy, typified by the need to differentiate whether gestational pruritus of the skin is an early symptom of intrahepatic cholestasis of pregnancy (ICP) or due to benign pruritus gravidarum. ICP is characterized by raised serum bile acids and complicated by spontaneous preterm labor and stillbirth. A biomarker for ICP would be invaluable for early diagnosis and treatment and to enable its differentiation from other maternal diseases. Three progesterone sulfate compounds, whose concentrations have not previously been studied, were newly synthesized and assayed in the serum of three groups of ICP patients and found to be significantly higher in ICP at 9‐15 weeks of gestation and prior to symptom onset (group 1 cases/s les: ICP n = 35/80, uncomplicated pregnancy = 29/100), demonstrating that all three progesterone sulfates are prognostic for ICP. Concentrations of progesterone sulfates were associated with itch severity and, in combination with autotaxin, distinguished pregnant women with itch that would subsequently develop ICP from pruritus gravidarum (group 2: ICP n = 41, pruritus gravidarum n = 14). In a third group of first‐trimester s les all progesterone sulfates were significantly elevated in serum from low‐risk asymptomatic women who subsequently developed ICP (ICP/uncomplicated pregnancy n = 54/51). Finally, we show mechanistically that progesterone sulfates mediate itch by evoking a Tgr5‐dependent scratch response in mice. Conclusion: Our discovery that sulfated progesterone metabolites are a prognostic indicator for ICP will help predict onset of ICP and distinguish it from benign pruritus gravidarum, enabling targeted obstetric care to a high‐risk population. Delineation of a progesterone sulfate‐TGR5 pruritus axis identifies a therapeutic target for itch management in ICP. (H epatology 2016 :1287–1298)
Publisher: Wiley
Date: 26-12-2014
Abstract: To compare the predictive value of the shock index (SI) with conventional vital signs in postpartum haemorrhage (PPH), and to establish 'alert' thresholds for use in low-resource settings. Retrospective cohort study. UK tertiary centre. Women with PPH ≥ 1500 ml (n = 233). Systolic blood pressure (BP), diastolic BP, mean arterial pressure, pulse pressure, heart rate (HR) and SI (HR/systolic BP) were measured within the first hour following PPH. Values measured at the time of highest SI were selected for analysis. The area under the receiver operating characteristic curve (AUROC) for each parameter, used to predict admission to an intensive care unit and other adverse outcomes, was calculated. Sensitivity, specificity and negative ositive predictive values determined thresholds of the best predictor. Intensive care unit (ICU) admission, blood transfusion ≥ 4 iu, haemoglobin level <7 g/dl, and invasive surgical procedures. Shock index has the highest AUROC to predict ICU admissions (0.75 for SI [95% CI 0.63-0.87] compared with 0.64 [95% CI 0.44-0.83] for systolic BP). SI compared favourably for other outcomes: SI ≥ 0.9 had 100% sensitivity (95% CI 73.5-100) and 43.4% specificity (95% CI 36.8-50.3), and SI ≥ 1.7 had 25.0% sensitivity (95% CI 5.5-57.2) and 97.7% specificity (CI 94.8-99.3), for predicting ICU admission. Shock index compared favourably with conventional vital signs in predicting ICU admission and other outcomes in PPH, even after adjusting for confounding SI <0.9 provides reassurance, whereas SI ≥ 1.7 indicates a need for urgent attention. In low-resource settings this simple parameter could improve outcomes. It was not possible to adjust for resuscitative measures administered following vital sign measurement that may have influenced the outcome.
Publisher: Wiley
Date: 03-07-2015
DOI: 10.1002/UOG.14860
Abstract: To assess the diagnostic accuracy of placental growth factor (PlGF) and ultrasound parameters to predict delivery of a small-for-gestational-age (SGA) infant in women presenting with reduced symphysis-fundus height (SFH). This was a multicenter prospective observational study recruiting 601 women with a singleton pregnancy and reduced SFH between 24 and 37 weeks' gestation across 11 sites in the UK and Canada. Plasma PlGF concentration < 5(th) centile, estimated fetal weight (EFW) 95(th) centile and oligohydramnios (amniotic fluid index < 5 cm) were compared as predictors for a SGA infant < 3(rd) customized birth-weight centile and adverse perinatal outcome. Test performance statistics were calculated for all parameters in isolation and in combination. Of the 601 women recruited, 592 were analyzed. For predicting delivery of SGA < 3(rd) centile (n = 78), EFW < 10(th) centile had 58% sensitivity (95% CI, 46-69%) and 93% negative predictive value (NPV) (95% CI, 90-95%), PlGF had 37% sensitivity (95% CI, 27-49%) and 90% NPV (95% CI, 87-93%) in combination, PlGF and EFW < 10(th) centile had 69% sensitivity (95% CI, 55-81%) and 93% NPV (95% CI, 89-96%). The equivalent receiver-operating characteristics (ROC) curve areas were 0.79 (95% CI, 0.74-0.84) for EFW < 10(th) centile, 0.70 (95% CI, 0.63-0.77) for low PlGF and 0.82 (95% CI, 0.77-0.86) in combination. For women presenting with reduced SFH, ultrasound parameters had modest test performance for predicting delivery of SGA < 3(rd) centile. PlGF performed no better than EFW < 10(th) centile in determining delivery of a SGA infant.
Publisher: Elsevier BV
Date: 05-2015
Abstract: Controversy surrounds the effectiveness of dietary guidelines for cardiovascular disease (CVD) prevention in healthy middle-aged and older men and women. The objective was to compare effects on vascular and lipid CVD risk factors of following the United Kingdom dietary guidelines with a traditional British diet (control). With the use of a parallel-designed randomized controlled trial in 165 healthy nonsmoking men and women (aged 40-70 y), we measured ambulatory blood pressure (BP) on 5 occasions, vascular function, and CVD risk factors at baseline and during 12 wk after random assignment to treatment. The primary outcomes were differences between treatments in daytime ambulatory systolic BP, flow-mediated dilation, and total cholesterol/HDL cholesterol. Secondary outcomes were differences between treatment in carotid-to-femoral pulse wave velocity, high-sensitivity C-reactive protein, and a measure of insulin sensitivity (Revised Quantitative Insulin Sensitivity Check Index). Data were available on 162 participants, and adherence to the dietary advice was confirmed from dietary records and biomarkers of compliance. In the dietary guidelines group (n = 80) compared with control (n = 82), daytime systolic BP was 4.2 mm Hg (95% CI: 1.7, 6.6 mm Hg P < 0.001) lower, the treatment effect on flow-mediated dilation [-0.62% (95% CI: -1.48%, 0.24%)] was not significant, the total cholesterol:HDL cholesterol ratio was 0.13 (95% CI: 0, 0.26 P = 0.044) lower, pulse wave velocity was 0.29 m/s (95% CI: 0.07, 0.52 m/s P = 0.011) lower, high-sensitivity C-reactive protein was 36% (95% CI: 7%, 48% P = 0.017) lower, the treatment effect on the Revised Quantitative Insulin Sensitivity Check Index [2% (95% CI: -2%, 5%)] was not significant, and body weight was 1.9 kg (95% CI: 1.3, 2.5 kg P < 0.001) lower. Causal mediated effects analysis based on urinary sodium excretion indicated that sodium reduction explained 2.4 mm Hg (95% CI: 1.0, 3.9 mm Hg) of the fall in blood pressure. Selecting a diet consistent with current dietary guidelines lowers BP and lipids, which would be expected to reduce the risk of CVD by one-third in healthy middle-aged and older men and women. This study is registered at www.isrctn.com as 92382106.
Publisher: Informa UK Limited
Date: 06-2020
Publisher: Public Library of Science (PLoS)
Date: 20-12-2016
Publisher: Wiley
Date: 24-09-2020
DOI: 10.1111/AOGS.13983
Abstract: Infection and inflammation have been implicated in the etiology and subsequent morbidity associated with preterm birth. At present, there are no tests to assess for fetal compartment infection. The thymus, a gland integral in the fetal immune system, has been shown to involute in animal models of antenatal infection, but its response in human fetuses has not been studied. This study aims: (a) to generate magnetic resonance imaging (MRI) -derived fetal thymus volumes standardized for fetal weight (b) to compare standardized thymus volumes from fetuses that delivered before 32 weeks of gestation with fetuses that subsequently deliver at term (c) to assess thymus size as a predictor of preterm birth and (d) to correlate the presence of chorioamnionitis and funisitis at delivery with thymic volumes in utero in fetuses that subsequently deliver preterm. Women at high-risk of preterm birth at 20-32 weeks of gestation were recruited. A control group was obtained from existing data sets acquired as part of three research studies. A fetal MRI was performed on a 1.5T or 3T MRI scanner: T2 weighted images were obtained of the entire uterine content and specifically the fetal thorax. A slice-to-volume registration method was used for reconstruction of three-dimensional images of the thorax. Thymus segmentations were performed manually. Body volumes were calculated by manual segmentation and thymus:body volume ratios were generated. Comparison of groups was performed using multiple regression analysis. Normal ranges were created for thymus volume and thymus:body volume ratios using the control data. Receiver operating curves (ROC) curves were generated for thymus:body volume ratio and gestation-adjusted thymus volume centiles as predictors of preterm birth. Placental histology was analyzed where available from pregnancies that delivered very preterm and the presence of chorioamnionitis/funisitis was noted. Normative ranges were created for thymus volume, and thymus volume was standardized for fetal size from fetuses that subsequently delivered at term, but were imaged at 20-32 weeks of gestation. Image data sets from 16 women that delivered 37 weeks were included. Mean gestation at MRI of the study group was 28 We have produced MRI-derived normal ranges for fetal thymus and thymus:body volume ratios between 20 and 32 weeks of gestation. Fetuses that deliver very preterm had reduced thymus volumes when standardized for fetal size. A reduced thymus volume was also a predictor of spontaneous preterm delivery. Thymus volume may be a suitable marker of the fetal inflammatory response, although further work is needed to assess this, increasing the s le size to correlate the extent of chorioamnionitis with thymus size.
Publisher: National Institute for Health and Care Research
Date: 12-2020
DOI: 10.3310/HTA24720
Abstract: Pre-ecl sia is a leading cause of maternal and perinatal mortality and morbidity. Early identification of women at risk is needed to plan management. To assess the performance of existing pre-ecl sia prediction models and to develop and validate models for pre-ecl sia using in idual participant data meta-analysis. We also estimated the prognostic value of in idual markers. This was an in idual participant data meta-analysis of cohort studies. Source data from secondary and tertiary care. We identified predictors from systematic reviews, and prioritised for importance in an international survey. Early-onset (delivery at 34 weeks’ gestation), late-onset (delivery at ≥ 34 weeks’ gestation) and any-onset pre-ecl sia. We externally validated existing prediction models in UK cohorts and reported their performance in terms of discrimination and calibration. We developed and validated 12 new models based on clinical characteristics, clinical characteristics and biochemical markers, and clinical characteristics and ultrasound markers in the first and second trimesters. We summarised the data set-specific performance of each model using a random-effects meta-analysis. Discrimination was considered promising for C -statistics of ≥ 0.7, and calibration was considered good if the slope was near 1 and calibration-in-the-large was near 0. Heterogeneity was quantified using I 2 and τ 2 . A decision curve analysis was undertaken to determine the clinical utility (net benefit) of the models. We reported the unadjusted prognostic value of in idual predictors for pre-ecl sia as odds ratios with 95% confidence and prediction intervals. The International Prediction of Pregnancy Complications network comprised 78 studies (3,570,993 singleton pregnancies) identified from systematic reviews of tests to predict pre-ecl sia. Twenty-four of the 131 published prediction models could be validated in 11 UK cohorts. Summary C -statistics were between 0.6 and 0.7 for most models, and calibration was generally poor owing to large between-study heterogeneity, suggesting model overfitting. The clinical utility of the models varied between showing net harm to showing minimal or no net benefit. The average discrimination for IPPIC models ranged between 0.68 and 0.83. This was highest for the second-trimester clinical characteristics and biochemical markers model to predict early-onset pre-ecl sia, and lowest for the first-trimester clinical characteristics models to predict any pre-ecl sia. Calibration performance was heterogeneous across studies. Net benefit was observed for International Prediction of Pregnancy Complications first and second-trimester clinical characteristics and clinical characteristics and biochemical markers models predicting any pre-ecl sia, when validated in singleton nulliparous women managed in the UK NHS. History of hypertension, parity, smoking, mode of conception, placental growth factor and uterine artery pulsatility index had the strongest unadjusted associations with pre-ecl sia. Variations in study population characteristics, type of predictors reported, too few events in some validation cohorts and the type of measurements contributed to heterogeneity in performance of the International Prediction of Pregnancy Complications models. Some published models were not validated because model predictors were unavailable in the in idual participant data. For models that could be validated, predictive performance was generally poor across data sets. Although the International Prediction of Pregnancy Complications models show good predictive performance on average, and in the singleton nulliparous population, heterogeneity in calibration performance is likely across settings. Recalibration of model parameters within populations may improve calibration performance. Additional strong predictors need to be identified to improve model performance and consistency. Validation, including examination of calibration heterogeneity, is required for the models we could not validate. This study is registered as PROSPERO CRD42015029349. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment Vol. 24, No. 72. See the NIHR Journals Library website for further project information.
Publisher: Springer Science and Business Media LLC
Date: 03-09-2018
Publisher: Public Library of Science (PLoS)
Date: 08-12-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2015
Publisher: Elsevier BV
Date: 12-2022
Publisher: Springer Science and Business Media LLC
Date: 08-01-2016
Publisher: Springer Science and Business Media LLC
Date: 21-01-2019
Publisher: Elsevier BV
Date: 09-2002
Abstract: We have previously reported a reduced incidence of preecl sia in women who were at risk and were taking vitamin C (1000 mg/d) and vitamin E (400 IU/d) supplements. In this study, we determined whether supplementation in the same cohort was associated with an improvement in indices of placental dysfunction and oxidative stress toward values determined in women who were at low risk of preecl sia. Seventy-nine women who were at high risk and who were taking vitamin supplements and 81 who were taking placebos were compared with 32 women who were at low risk and who were not taking supplements who were studied simultaneously. Indices of oxidative stress and placental function were abnormal in the placebo group. When the placebo group was compared with the women who were at low risk, ascorbic acid, plasminogen activator inhibitor-2, and placenta growth factor concentrations were decreased and 8-epi-prostaglandin F(2alpha),leptin, and the plasminogen activator inhibitor-1/-2 ratio were increased. In the group that received vitamin supplements, ascorbic acid, 8-epi-prostaglandin F(2alpha), leptin, and plasminogen activator inhibitor-1/-2 values were similar to women who were at low risk. Antioxidant supplementation in women who were at risk of preecl sia was associated with improvement in biochemical indices of the disease.
Publisher: Springer Science and Business Media LLC
Date: 02-09-2022
DOI: 10.1186/S13063-022-06652-8
Abstract: Pre-ecl sia is a complex pregnancy disorder, characterised by new or worsening hypertension associated with multi-organ dysfunction. Adverse outcomes include ecl sia, liver rupture, stroke, pulmonary oedema, and acute kidney injury in the mother, and stillbirth, foetal growth restriction, and iatrogenic preterm delivery for the foetus. Angiogenic biomarkers, including placental growth factor (PlGF) and soluble fms-like tyrosine kinase 1 (sFlt-1), have been identified as valuable biomarkers for preterm pre-ecl sia, accelerating diagnosis and reducing maternal adverse outcomes by risk stratification, with enhanced surveillance for high-risk women. PlGF-based testing for suspected preterm pre-ecl sia has been incorporated into national guidance. The role of repeat PlGF-based testing and its effect on maternal and perinatal adverse outcomes have yet to be evaluated. The PARROT-2 trial is a multi-centre randomised controlled trial of repeat revealed PlGF-based testing compared to repeat concealed testing, in women presenting with suspected pre-ecl sia between 22 +0 and 35 +6 weeks’ gestation. The primary objective is to establish whether repeat PlGF-based testing decreases a composite of perinatal severe adverse outcomes (stillbirth, early neonatal death, or neonatal unit admission). All women prior to enrolment in the trial will have an initial revealed PlGF-based test. Repeat PlGF-based tests will be performed weekly or two-weekly, depending on the initial PlGF-based test result, with results randomised to revealed or concealed. National guidance recommends that all women presenting with suspected preterm pre-ecl sia should have a single PlGF-based test when disease is first suspected, to help rule out pre-ecl sia. Clinical and cost-effectiveness of repeat PlGF-based testing has yet to be investigated. This trial aims to address whether repeat PlGF-based testing reduces severe maternal and perinatal adverse outcomes and whether repeat testing is cost-effective. ISRCTN 85912420 . Registered on 25 November 2019
Publisher: Springer Science and Business Media LLC
Date: 07-2011
Abstract: To evaluate pregnancy outcome in women with chronic kidney disease (CKD) or proteinuria in early pregnancy with concomitant risk for preecl sia (PE). Thirty-six women with CKD (Cr > 100 μmol/L at booking or Cr > 125 μmol/L prepregnancy or proteinuria ≥ 500 mg/24 hours at booking) and 30 women with proteinuria (≥2+) and known clinical risk for PE were enrolled at 14(+0) to 21(+6) weeks. Pregnancy outcomes were assessed. Women with mild CKD (prepregnancy Cr 100 µmol at booking n = 22) had high rates of preecl sia (40%), preterm delivery (<37 weeks' gestation 54%), SGA infants ( 125 µmol n = 14) had poor perinatal outcomes: preterm delivery (86%) and perinatal death (14%). Women with proteinuria (≥2+) and concomitant risk of PE also had high rates of pre-ecl sia (60%), preterm delivery (40%), and SGA infants (27%). Pregnancy complications for women with CKD remain high. Women with risk factors for PE with proteinuria (≥2+) at booking are also high-risk.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2019
Publisher: National Institute for Health and Care Research
Date: 11-2022
DOI: 10.3310/CWWH0622
Abstract: In women with late preterm pre-ecl sia (i.e. at 34 +0 to 36 +6 weeks’ gestation), the optimal delivery time is unclear because limitation of maternal–fetal disease progression needs to be balanced against infant complications. The aim of this trial was to determine whether or not planned earlier initiation of delivery reduces maternal adverse outcomes without substantial worsening of perinatal or infant outcomes, compared with expectant management, in women with late preterm pre-ecl sia. We undertook an in idually randomised, triple non-masked controlled trial in 46 maternity units across England and Wales, with an embedded health economic evaluation, comparing planned delivery and expectant management (usual care) in women with late preterm pre-ecl sia. The co-primary maternal outcome was a maternal morbidity composite or recorded systolic blood pressure of ≥ 160 mmHg (superiority hypothesis). The co-primary short-term perinatal outcome was a composite of perinatal deaths or neonatal unit admission (non-inferiority hypothesis). Analyses were by intention to treat, with an additional per-protocol analysis for the perinatal outcome. The primary 2-year infant neurodevelopmental outcome was measured using the PARCA-R (Parent Report of Children’s Abilities-Revised) composite score. The planned s le size of the trial was 900 women the trial is now completed. We undertook two linked substudies. Between 29 September 2014 and 10 December 2018, 901 women were recruited 450 women [448 women (two withdrew consent) and 471 infants] were allocated to planned delivery and 451 women (451 women and 475 infants) were allocated to expectant management. The incidence of the co-primary maternal outcome was significantly lower in the planned delivery group [289 (65%) women] than in the expectant management group [338 (75%) women] (adjusted relative risk 0.86, 95% confidence interval 0.79 to 0.94 p = 0.0005). The incidence of the co-primary perinatal outcome was significantly higher in the planned delivery group [196 (42%) infants] than in the expectant management group [159 (34%) infants] (adjusted relative risk 1.26, 95% confidence interval 1.08 to 1.47 p = 0.0034), but indicators of neonatal morbidity were similar in both groups. At 2-year follow-up, the mean PARCA-R scores were 89.5 points (standard deviation 18.2 points) for the planned delivery group (290 infants) and 91.9 points (standard deviation 18.4 points) for the expectant management group (256 infants), both within the normal developmental range (adjusted mean difference –2.4 points, 95% confidence interval –5.4 to 0.5 points non-inferiority p = 0.147). Planned delivery was significantly cost-saving (–£2711, 95% confidence interval –£4840 to –£637) compared with expectant management. There were nine serious adverse events in the planned delivery group and 12 in the expectant management group. In women with late preterm pre-ecl sia, planned delivery reduces short-term maternal morbidity compared with expectant management, with more neonatal unit admissions related to prematurity but no indicators of greater short-term neonatal morbidity (such as need for respiratory support). At 2-year follow-up, around 60% of parents reported follow-up scores. Average infant development was within the normal range for both groups the small between-group mean difference in PARCA-R scores is unlikely to be clinically important. Planned delivery was significantly cost-saving to the health service. These findings should be discussed with women with late preterm pre-ecl sia to allow shared decision-making on timing of delivery. Limitations of the trial include the challenges of finding a perinatal outcome that adequately represented the potential risks of both groups and a maternal outcome that reflects the multiorgan manifestations of pre-ecl sia. The incidences of maternal and perinatal primary outcomes were higher than anticipated on the basis of previous studies, but this did not limit interpretation of the analysis. The trial was limited by a higher loss to follow-up rate than expected, meaning that the extent and direction of bias in outcomes (between responders and non-responders) is uncertain. A longer follow-up period (e.g. up to 5 years) would have enabled us to provide further evidence on long-term infant outcomes, but this runs the risk of greater attrition and increased expense. We identified a number of further questions that could be prioritised through a formal scoping process, including uncertainties around disease-modifying interventions, prognostic factors, longer-term follow-up, the perspectives of women and their families, meta-analysis with other studies, effect of a similar intervention in other health-care settings, and clinical effectiveness and cost-effectiveness of other related policies around neonatal unit admission in late preterm birth. The trial was prospectively registered as ISRCTN01879376. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in Health Technology Assessment . See the NIHR Journals Library website for further project information.
Publisher: Elsevier BV
Date: 04-2006
Publisher: Springer Science and Business Media LLC
Date: 20-04-2020
DOI: 10.1186/S13063-020-4212-8
Abstract: Pregnancies in women with sickle cell disease (SCD) are associated with a higher risk of sickle and pregnancy complications. Limited options exist for treating SCD during pregnancy. Serial prophylactic exchange blood transfusion (SPEBT) has been shown to be effective in treating SCD outside pregnancy, but evidence is lacking regarding its use during pregnancy. The aim of this study is to assess the feasibility and acceptability of conducting a future phase 3 randomised controlled trial (RCT) to establish the clinical and cost effectiveness of SPEBT in pregnant women with SCD. The study is an in idually randomised, two-arm, feasibility trial with embedded qualitative and health economic studies. Fifty women, 18 years of age and older, with SCD and a singleton pregnancy at ≤ 18 weeks’ gestation will be recruited from six hospitals in England. Randomisation will be conducted using a secure online database and minimised by centre, SCD genotype and maternal age. Women allocated to the intervention arm will receive SPEBT commencing at ≤ 18 weeks’ gestation, performed using automated erythrocytapheresis every 6–10 weeks until the end of pregnancy, aiming to maintain HbS% or combined HbS/HbC% below 30%. Women in the standard care arm will only receive transfusion when clinically indicated. The primary outcome will be the recruitment rate. Additional endpoints include reasons for refusal to participate, attrition rate, protocol adherence, and maternal and neonatal outcomes. Women will be monitored throughout pregnancy to assess maternal, sickle, and foetal complications. Detailed information about adverse events (including hospital admission) and birth outcomes will be extracted from medical records and via interview at 6 weeks postpartum. An embedded qualitative study will consist of interviews with (a) 15–25 trial participants to assess experiences and acceptability, (b) 5–15 women who decline to participate to identify barriers to recruitment and (c) 15–20 clinical staff to explore fidelity and acceptability. A health economic study will inform a future cost effectiveness and cost-utility analysis. This feasibility study aims to rigorously evaluate SPEBT as a treatment for SCD in pregnancy and its impact on maternal and infant outcomes. NIH registry ( www.clinicaltrials.gov ), registration number NCT03975894 (registered 05/06/19) ISRCTN ( www.isrctn.com ), registration number ISRCTN52684446 (retrospectively registered 02/08/19).
Publisher: Springer Science and Business Media LLC
Date: 05-11-2020
DOI: 10.1186/S12884-020-03332-W
Abstract: The fullPIERS risk prediction model was developed to identify which women admitted with confirmed diagnosis of preecl sia are at highest risk of developing serious maternal complications. The model discriminates well between women who develop (vs. those who do not) adverse maternal outcomes. It has been externally validated in several populations. We assessed whether placental growth factor (PlGF), a biomarker associated with preecl sia risk, adds incremental value to the fullPIERS model. Using a cohort of women admitted into tertiary hospitals in well-resourced settings (the USA and Canada), between May 2010 to February 2012, we evaluated the incremental value of PlGF added to fullPIERS for prediction of adverse maternal outcomes within 48 h after admission with confirmed preecl sia. The discriminatory performance of PlGF and the fullPIERS model were assessed in this cohort using the area under the receiver’s operating characteristic curve (AUROC) while the extended model (fullPIERS +PlGF) was assessed based on net reclassification index (NRI) and integrated discrimination improvement (IDI) performances. In a cohort of 541 women delivered shortly ( 1 week) after presentation, 8.1% experienced an adverse maternal outcome within 48 h of admission. Prediction of adverse maternal outcomes was not improved by addition of PlGF to fullPIERS (NRI: -8.7, IDI − 0.06). Discriminatory performance (AUROC) was 0.67 [95%CI: 0.59–0.75] for fullPIERS only and 0.67 [95%CI: 0.58–0.76]) for fullPIERS extended with PlGF, a performance worse than previously documented in fullPIERS external validation studies (AUROC 0.75). While fullPIERS model performance may have been affected by differences in healthcare context between this study cohort and the model development and validation cohorts, future studies are required to confirm whether PlGF adds incremental benefit to the fullPIERS model for prediction of adverse maternal outcomes in preecl sia in settings where expectant management is practiced.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2001
DOI: 10.1046/J.1524-4725.2001.00108.X
Abstract: The immediate effects of CO2 laser resurfacing include tissue ablation and residual thermal damage. These laser-tissue interactions are shaped by parameters including fluence, dwell time, and number of passes. To assess the vaporization depth and residual thermal damage following use of the "superficial" or "deep" scanning modes of a 40 W continuous wave CO2 laser using both frozen and paraffin sections. Fourteen subjects were ided into two groups for test treatments in the right preauricular area with two passes of the laser. The "superficial" mode parameters were 10 mm2 scan, 200 mm lens, power 36 W, scan time 0.24 seconds, dwell time 0.22 msec, and fluence 5.5 J/cm2. The "deep" mode settings were 9 mm2 scan, 200 mm lens, power 18 W, scan time 0.64 seconds, dwell time 0.28 msec, and fluence 7.0 J/cm2. The deep mode has a greater pattern density than the superficial mode and also has a double pattern of exposure. Biopsies encompassing equal areas of treated and untreated skin were taken immediately postoperatively and processed with both frozen and paraffin-embedded techniques. Vaporization depth was similar in both scanning modes and by both tissue-processing techniques. On frozen sections, residual thermal damage was 20% greater in the deep mode than the superficial mode, but this was not a statistically significant difference. There was no significant difference between the two modes in the depth of thermal injury on paraffin sections. In keeping with theoretical expectations, vaporization depth was similar in both treatment groups. No significant difference in residual thermal damage could be demonstrated between the two modes. However, the results on frozen sections suggest that residual thermal damage may be greater in the deep mode than in the superficial mode. In addition, frozen sections may be more sensitive than paraffin sections in the detection of residual thermal damage following laser resurfacing.
Publisher: Elsevier BV
Date: 07-2006
Publisher: Wiley
Date: 05-12-2018
DOI: 10.1002/UOG.19051
Publisher: Springer Science and Business Media LLC
Date: 18-09-2018
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.EJOGRB.2019.04.034
Abstract: Frances Conti-Ramsden MBBS Academic Clinical Fellow To determine whether glycogen phosphorylase isoenzyme B (GPBB) and/or brain natriuretic peptide (BNP) concentrations are elevated in pre-ecl sia and superimposed pre-ecl sia (SPE), demonstrating cardiac ischaemia and strain. A nested case-control study was performed using s les and clinical data available from a prospective pregnancy cohort. Four groups were selected: healthy pregnant controls (n = 21), pre-ecl sia (n = 19), pre-existing chronic hypertension (CHT) and/or chronic kidney disease (CKD) without (n = 20) or with superimposed pre-ecl sia (SPE) (n = 19). Plasma s les were taken at time of disease or the third trimester in controls. Plasma concentrations of GPBB and BNP. There was no significant difference in GPBB plasma concentrations between controls and pre-ecl sia (geometric mean (GM) [95% CI]: 4.74 [2.54-8.84]ng/mL vs 5.01 [2.58-9.74]ng/mL, p = 0.90)), or between CHT and/or CKD and SPE (GM [95% CI]: 9.49 [4.93-18.25]ng/mL vs 10.24 [5.27-19.92]ng/mL, p = 0.87). BNP plasma concentrations were significantly raised in women with pre-ecl sia compared to controls (GM [95% CI]: 31.83 [20.18-50.22]pg/mL vs 11.33 [7.34-17.51]pg/mL, p = 0.001). Women with CKD, but not CHT, who developed SPE had elevated BNP concentrations. There were no significant differences in BNP concentration between women with comorbidity (CHT and/or CKD) and controls. GPBB has a limited role as a biomarker in hypertensive disorders of pregnancy. BNP concentrations were elevated in pre-ecl sia compared to controls. This suggests cardiac strain at the time of pre-ecl sia. Further studies are needed to examine whether BNP can identify women at increased risk of cardiovascular disease.
Publisher: Elsevier BV
Date: 06-2011
Publisher: Public Library of Science (PLoS)
Date: 14-10-2016
Publisher: Springer Science and Business Media LLC
Date: 07-10-2019
DOI: 10.1186/S12884-019-2445-X
Abstract: Preecl sia (PE) is a major cause of short and long-term morbidity for affected infants, including consequences of fetal growth restriction and iatrogenic prematurity. In Brazil, this is a special problem as PE accounts for 18% of preterm births (PTB). In the PREPARE (Prematurity REduction by Pre-ecl sia cARE) study, we will test a novel system of integrated care based on risk stratification and knowledge transfer, to safely reduce PTB. This is a stepped wedge cluster randomised trial that will include women with suspected or confirmed PE between 20 + 0 and 36 + 6 gestational weeks. All pregnant women presenting with these findings at seven tertiary centres in geographically dispersed sites, throughout Brazil, will be considered eligible and evaluated in terms of risk stratification at admission. At randomly allocated time points, sites will transition to risk stratification performed according to sFlt-1/PlGF (Roche Diagnostics) measurement and fullPIERS score with both results will be revealed to care providers. The healthcare providers of women stratified as low risk for adverse outcomes (sFlt-1/PlGF ≤38 AND fullPIERS 10% risk) will receive the recommendation to defer delivery. sFlt-1/PlGF will be repeated once and fullPIERS score twice a week. Rates of prematurity due to preecl sia before and after the intervention will be compared. Additionally, providers will receive an active program of knowledge transfer about WHO recommendations for preecl sia, including recommendations regarding antenatal corticosteroids for foetal benefits, antihypertensive therapy and magnesium sulphate for seizure prophylaxis. This study will have 90% power to detect a reduction in PTB associated with PE from a population estimate of 1.5 to 1.0%, representing a 33% risk reduction, and 80% power to detect a reduction from 2.0 to 1.5% (25% risk reduction). The necessary number of patients recruited to achieve these results is 750. Adverse events, serious adverse events, both anticipated and unanticipated will be recorded. The PREPARE intervention expects to reduce PTB and improve care of women with PE without significant adverse side effects. If successful, this novel pathway of care is designed for rapid translation to healthcare throughout Brazil and may be transferrable to other low and middle income countries. ClinicalTrials.gov : NCT03073317.
Publisher: Springer Science and Business Media LLC
Date: 07-12-2019
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.AJOG.2008.10.047
Abstract: We sought to investigate pregnancy outcome and biomarkers of oxidative stress in nulliparous obese pregnant women. Pregnancy outcome and blood biomarkers were assessed prospectively in 385 obese nulliparous women from the placebo arm of a randomized controlled trial. Body mass index was associated with higher rates of preecl sia (PE) (P = .010) and cesarean section (P = .016). In all, 18.8% of infants were small for gestational age ( 90th centile), and 11.9% were preterm. The plasma ascorbic acid concentration was inversely related to small-for-gestational-age delivery (P < .025), and increased plasma triglyceride concentrations with later PE (P < .0001). Plasma uric acid concentration (P = .043) and the gamma- tocopherol:alpha-tocopherol ratio (P = .023) were related to body mass index. A previously unreported risk of fetal growth restriction associated with reduced plasma ascorbic acid concentration was identified in nulliparous obese women. The high incidence of PE and preterm birth were unrelated to oxidative stress markers.
Publisher: Informa UK Limited
Date: 13-09-2016
DOI: 10.1080/01443615.2016.1217514
Abstract: The aim of this study was to assess a new device (Tydeman Tube) designed to facilitate delivery of the impacted foetal head at caesarean section. Standard digital vaginal technique and the Tydeman Tube were each used to elevate the foetal head on a validated full dilatation caesarean simulator. Greater elevation of the foetal head was achieved with the Tydeman Tube than digital technique (mean difference +9.1 mm, p < 0.001). Although greater force was applied to achieve this elevation (mean difference +0.42 Kgf, p < 0.001), the force was spread over a greater area (6.97 cm
Publisher: Wiley
Date: 14-09-2007
Publisher: National Institute for Health and Care Research
Date: 09-2021
DOI: 10.3310/EME08120
Abstract: Women whose pregnancies are affected by hypertensive disorders of pregnancy, in particular preterm pre-ecl sia, are at increased risk of long-term cardiovascular morbidity and mortality. To investigate the hypothesis that prolongation of a pregnancy affected by preterm pre-ecl sia managed by expectant management compared with planned early delivery would result in worse cardiovascular function 6 months postpartum. A randomised controlled trial. 28 maternity hospitals in England and Wales. Women who were eligible for the Pre-ecl sia in HOspital: Early iNductIon or eXpectant management (PHOENIX) study were approached and recruited for the PHOEBE study. The PHOENIX (Pre-ecl sia in HOspital: Early iNductIon or eXpectant management) study was a parallel-group, non-masked, multicentre, randomised controlled trial that was carried out in 46 maternity units across England and Wales. This study compared planned early delivery with expectant management (usual care) with in idual randomisation in women with late preterm pre-ecl sia who were 34 weeks’ gestation to less than 37 weeks’ gestation and having a singleton or dichorionic diamniotic twin pregnancy. Postpartum follow-up included medical history, blood pressure assessment and echocardiography. All women had blood s ling performed on at least two time points from recruitment to the 6-month follow-up for assessment of cardiac necrosis markers. Primary outcome was a composite of systolic and/or diastolic dysfunction (originally by 2009 guidelines then updated by 2016 guidelines, with an amended definition of diastolic dysfunction). Analyses were by intention to treat, together with a per-protocol analysis for the primary and secondary outcomes. Between 27 April 2016 and 30 November 2018, 623 women were found to be eligible, of whom 420 (67%) were recruited across 28 maternity units in England and Wales. A total of 133 women were allocated to planned delivery, 137 women were allocated to expectant management and a further 150 received non-randomised expectant management within usual care. The mean time from enrolment to delivery was 2.5 (standard deviation 1.9) days in the planned delivery group compared with 6.8 (standard deviation 5.3) days in the expectant management group. There were no differences in the primary outcome between women in the planned delivery group and those in the expectant management group using either the 2009 (risk ratio 1.06, 95% confidence interval 0.80 to 1.40) or the 2016 definition (risk ratio 0.78, 95% confidence interval 0.33 to 1.86). Overall, 10% (31/321) of women had a left ventricular ejection fraction 55% and 71% of the cohort remained hypertensive at 6 months postpartum. No differences were observed between groups in cardiorespiratory outcomes prior to discharge from hospital or in systolic or diastolic blood pressure measurements. Variables associated with the primary outcome (2009 definition) at 6 months postpartum were maternal body mass index (adjusted odds ratio 1.33 per 5 kg/m 2 , 95% confidence interval 1.12 to 1.59 per 5 kg/m 2 ) and maternal age (adjusted odds ratio 2.16, 95% confidence interval 1.44 to 3.22 per 10 years). Limitations include changing definitions regarding systolic and/or diastolic dysfunction. Preterm pre-ecl sia results in persistence of hypertension in the majority of women with late preterm pre-ecl sia at 6 months postpartum and systolic dysfunction in 10%. Pre-ecl sia should not be considered a self-limiting disease of pregnancy alone. Interventions aimed at reducing cardiovascular dysfunction. Current Controlled Trials ISRCTN01879376. This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation Vol. 8, No. 12. See the NIHR Journals Library website for further project information.
Publisher: Public Library of Science (PLoS)
Date: 20-09-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2021
Publisher: Wiley
Date: 16-09-2009
DOI: 10.1111/J.1471-0528.2009.02293.X
Abstract: Saliva progesterone and oestriol concentrations were determined weekly from 24 weeks of gestation in women at increased risk of preterm delivery. S les were analysed from 28 women with spontaneous onset of labour and delivery before 37 weeks of gestation, and 64 who delivered at term. Saliva progesterone was lower in the 12 women delivering before 34 weeks than in those delivering later, between 34 and 37 weeks (P = 0.007) or at term (P = 0.009). Measurement of saliva progesterone may be of value in the prediction of early preterm labour and in determining which women might benefit from progesterone supplementation.
Publisher: Springer Science and Business Media LLC
Date: 19-07-2022
DOI: 10.1186/S13063-022-06462-Y
Abstract: Each year in the UK, approximately 35,000 women develop gestational diabetes mellitus (GDM). The condition increases the risk of obstetric and neonatal complications for mother and child, including preecl sia, preterm birth, and large for gestational age babies. Biochemical consequences include maternal hyperglycemia, neonatal hypoglycemia, and dyslipidemia. Metformin is the most commonly used firstline pharmacological treatment. However, there are concerns about its widespread use during pregnancy, due to its limited efficacy and potential safety concerns. Therefore, there is a need for additional therapies that improve both maternal–fetal glucose and lipid metabolism. Ursodeoxycholic acid (UDCA) is not currently used for treatment for GDM. However, it can improve glucose control in type 2 diabetes, and it improves fetal lipid profiles in gestational cholestasis. Consequentially, it is hypothesized that treatment with UDCA for women with GDM may improve both maternal metabolism and neonatal outcomes. The primary outcome of this trial is to assess the efficacy of UDCA compared with metformin to improve glucose levels in women with GDM. The trial is a two-armed, open-label, multi-center, randomized controlled trial. Women are eligible if they have been diagnosed with GDM by an oral glucose tolerance test between 24 + 0 and 30 + 6 weeks’ gestation, and if they require pharmacological intervention. In total, 158 pregnant women will be recruited across seven NHS Trusts in England and Wales. Women who consent will be recruited and randomized to either metformin or UDCA, which will be taken daily until the birth of their baby. Maternal and neonatal blood s les will be taken to evaluate the impact of the treatments on maternal glucose control, and maternal and neonatal lipid metabolism. Maternal and fetal outcomes will be evaluated, and acceptability of UDCA compared with metformin will be assessed. This trial has the potential to identify a potential new treatment for women with GDM. If successful, a future large multi-center trial will be designed to investigate where decisions can be personalized to identify which women will respond more effectively to UDCA than alternatives to improve maternal and baby outcomes. ClinicalTrials.gov NCT04407650.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2008
DOI: 10.1161/HYPERTENSIONAHA.107.107565
Abstract: Prospective contemporaneous data on the outcome of pregnancies in women with chronic hypertension are sparse. Indices of maternal and perinatal morbidity and mortality were determined in 822 women with chronic hypertension with data prospectively collected and rigorously validated. The incidence of superimposed preecl sia was 22% (n=180) with early-onset preecl sia (≤34 weeks gestation) accounting for nearly half of these cases. Delivering an infant th customized birthweight centile complicated 48% (87/180) of those with superimposed preecl sia and 21% (137/642) in those without (relative risk [RR] 2.30 95% confidence intervals [CI] 1.85 to 2.84). Delivery at weeks gestation occurred in 51% of those with superimposed preecl sia (98% of these iatrogenic) and 15% without (66% iatrogenic) (RR 3.52 95% CI 2.79 to 4.45). Using multiple logistic regression, black ethnic origin, raised body mass index, present smoking, booking systolic blood pressure of 130 to 139 mm Hg, and diastolic blood pressure of 80 to 89 mm Hg, a previous history of preecl sia or ecl sia and chronic renal disease were identified as risk factors for superimposed preecl sia. Adverse maternal and perinatal outcomes occur in women with chronic hypertension the prevalence of infants born small for gestational age and preterm is considerably higher than background rates, and is increased further in women with superimposed preecl sia. Use of customized birthweight centiles provides more accurate determination of fetal growth restriction and highlights the need for greater fetal surveillance in these women. Paradoxically, smoking is an independent risk factor for superimposed preecl sia in chronic hypertension, in contrast to the protective effect in low-risk pregnant women.
Publisher: Springer Science and Business Media LLC
Date: 03-11-2017
Publisher: BMJ
Date: 17-11-2021
DOI: 10.1136/ARCHDISCHILD-2021-322860
Abstract: Maternal obesity may increase offspring risk of cardiovascular disease. We assessed the impact of maternal obesity on cardiac structure and function in newborns as a marker of fetal cardiac growth. Neonates born to mothers of healthy weight (body mass index (BMI) 20–25 kg/m 2 , n=56) and to mothers who were obese (BMI ≥30 kg/m 2 , n=31) underwent 25-minute continuous ECG recording and non-sedated, free-breathing cardiac MRI within 72 hours of birth. Mean (SD) heart rate during sleep was higher in infants born to mothers who were versus were not obese (123 (12.6) vs 114 (9.8) beats/min, p=0.002). Heart rate variability during sleep was lower in infants born to mothers who were versus were not obese (SD of normal-to-normal R-R interval 34.6 (16.8) vs 43.9 (16.5) ms, p=0.05). Similar heart rate changes were seen during wakefulness. Left ventricular end-diastolic volume (2.35 (0.14) vs 2.54 (0.29) mL/kg, p=0.03) and stroke volume (1.50 (0.09) vs 1.60 (0.14), p=0.04) were decreased in infants born to mothers who were versus were not obese. There were no differences in left ventricular end-systolic volume, ejection fraction, output or myocardial mass between the groups. Maternal obesity was associated with increased heart rate, decreased heart rate variability and decreased left ventricular volumes in newborns. If persistent, these changes may provide a causal mechanism for the increased cardiovascular risk in adult offspring of mothers with obesity. In turn, modifying antenatal and perinatal maternal health may have the potential to optimise long-term cardiovascular health in offspring.
Publisher: Elsevier BV
Date: 05-1992
Publisher: Elsevier BV
Date: 07-2018
Publisher: Springer Science and Business Media LLC
Date: 29-11-2016
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2002
DOI: 10.1097/00000539-200211000-00057
Abstract: We conducted a prospective, randomized, controlled trial to establish the effect of epidural blockade on isoflurane requirements for equivalent intraoperative electroencephalographic (EEG) suppression. Fifty patients undergoing abdominal hysterectomy received combined epidural and general anesthesia or general anesthesia alone with isoflurane and alfentanil. Isoflurane was administered by computer-controlled closed-loop feedback to maintain an EEG 95% spectral edge frequency of 17.5 Hz, a target chosen on the basis of a pilot study. In epidural patients, end-tidal isoflurane concentration (FE'(ISO)) was 0.19% smaller (95% confidence interval [CI], -0.32% to -0.06% P < 0.01), mean arterial blood pressure was 17 mm Hg lower (95% CI, -24 to -9 mm Hg P < 0.0001), and body temperature was 0.4 degrees C lower (95% CI, -0.7 to 0 degrees C P < 0.05) than in controls. EEG bispectral index (BIS) was 4 points higher (95% CI, 1 to 7 P < 0.05). EEG median frequency and heart rate were similar in both groups. Epidural patients were 76% more likely (95% CI, 58% to 94% P < 0.001) to require metaraminol for hypotension and were 28% more likely (95% CI, 3% to 53% P < 0.05) to require glycopyrrolate for bradycardia. After surgery, the time to eye opening in epidural patients was 2.3 min shorter (95% CI, -4.2 to -0.5 min P < 0.05). Time to eye opening correlated better with FE'(ISO) in the last 30 s of anesthesia (FE'(ISO) = 0.07 x time to eye opening + 0.31 r(2) = 0.59 P < 0.0001) than with BIS from the same period (BIS = 64 - 1.25 x time to eye opening r(2) = 0.22 P < 0.001) (P < 0.0001). To maintain similar intraoperative spectral edge frequency, patients receiving combined epidural and general anesthesia require 21% less isoflurane than those receiving general anesthesia alone. This smaller isoflurane dose is associated with faster emergence from anesthesia. The dose of general anesthetic required to maintain similar intraoperative suppression of brain electrical activity is 21% less in patients with nerve blockade than in those without. This dose reduction results in faster waking times in patients with nerve blockade, which may reflect lighter intraoperative anesthesia. The dose of general anesthetic required to maintain similar intraoperative suppression of brain electrical activity is 21% less in patients with nerve blockade than in those without. This dose reduction results in faster waking times in patients with nerve blockade, which may reflect lighter intraoperative anesthesia.
Publisher: The Endocrine Society
Date: 13-11-2017
Abstract: Offspring exposed in utero to maternal obesity have an increased risk of later obesity however, the underlying mechanisms remain unknown. To assess the effect of an antenatal lifestyle intervention in obese women on the offspring’s cord blood metabolic profile and to examine associations of the cord blood metabolic profile with maternal clinical characteristics and offspring anthropometry at birth and age 6 months. Randomized controlled trial and cohort study. The UK Pregnancies Better Eating and Activity Trial. Three hundred forty-four mother-offspring pairs. Antenatal behavioral lifestyle (diet and physical activity) intervention. Targeted cord blood metabolic profile, including candidate hormone and metabolomic analyses. The lifestyle intervention was not associated with change in the cord blood metabolic profile. Higher maternal glycemia, specifically fasting glucose at 28 weeks gestation, had a linear association with higher cord blood concentrations of lysophosphatidylcholines (LPCs) 16.1 (β = 0.65 95% confidence interval: 0.03 to 0.10) and 18.1 (0.52 0.02 to 0.80), independent of the lifestyle intervention. A principal component of cord blood phosphatidylcholines and LPCs was associated with infant z scores of birth weight (0.04 0.02 to 0.07) and weight at age 6 months (0.05 0.00 to 0.10). Cord blood insulin growth factor (IGF)-1 and adiponectin concentrations were positively associated with infant weight z score at birth and at 6 months. Concentrations of LPCs and IGF-1 in cord blood are related to infant weight. These findings support the hypothesis that susceptibility to childhood obesity may be programmed in utero, but further investigation is required to establish whether these associations are causally related.
Publisher: Public Library of Science (PLoS)
Date: 10-10-2013
Publisher: Elsevier BV
Date: 07-2002
Abstract: The purpose of this study was to characterize gestational profiles of biochemical markers that are associated with preecl sia in the blood of pregnant women in whom preecl sia developed later and to compare these markers with the markers of women who were delivered of small-for-gestational-age infants without preecl sia and with women who were at low risk for the development of preecl sia. This was a prospective case control study. The subjects were women at risk of preecl sia who were enrolled in the placebo arm of a clinical trial. Indices of antioxidant status, oxidative stress, placental and endothelial function, and serum lipid concentrations were evaluated from 20 weeks of gestation until delivery in 21 women in whom preecl sia developed later, in 17 women without preecl sia who were delivered of small-for-gestational-age infants, and in 27 women who were at low risk for the development of preecl sia. Ascorbic acid was reduced early in preecl sia and small-for-gestational-age pregnancies. Leptin, placenta growth factor, the plasminogen activator inhibitor (PAI-1)/PAI-2 ratio, and uric acid were predictive of the development of preecl sia. Gestational profiles of several markers were abnormal in the group with preecl sia, and some of the markers that may prove useful in the selective prediction of preecl sia were identified.
Publisher: Elsevier BV
Date: 10-2015
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Publisher: Springer Science and Business Media LLC
Date: 20-02-2017
DOI: 10.1038/IJO.2017.44
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Paul T Seed.