RESUMO
Abnormal maternal serum biomarkers (AMSB), identified through the aneuploidy screening programme, are frequent incidental findings in pregnancy. They are associated with fetal growth restriction (FGR), but previous studies have not examined whether this association is with early-onset (< 34 weeks) or late-onset (> 34 weeks) FGR; as a result there is no consensus on management. The aims of this study were to determine the prevalence and phenotype of FGR in women with AMSB and test the predictive value of placental sonographic screening to predict early-onset FGR. 1196 pregnant women with AMSB underwent a 21-24 week "placental screen" comprising fetal and placental size, and uterine artery Doppler. Multivariable regression was used to calculate a predictive model for early-onset FGR (birthweight centile < 3rd/< 10th with absent umbilical end-diastolic flow, < 34 weeks). FGR prevalence was high (10.3%), however early-onset FGR was uncommon (2.3%). Placental screening effectively identified early-onset (area under the curve (AUC) 0.93, 95% confidence interval (CI) 0.87-1.00), but not late-onset FGR (AUC 0.70, 95% CI 0.64-0.75). Internal validation demonstrated robust performance for detection/exclusion of early-onset FGR. In this cohort, utilisation of our proposed algorithm with targeted fetal growth and Doppler surveillance, compared with universal comprehensive surveillance would have avoided 1044 scans, potentiating significant cost-saving for maternity services.
Assuntos
Biomarcadores/sangue , Retardo do Crescimento Fetal/sangue , Recém-Nascido Pequeno para a Idade Gestacional/sangue , Placenta/diagnóstico por imagem , Adulto , Área Sob a Curva , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Idade Gestacional , Humanos , Recém-Nascido , Placenta/patologia , Valor Preditivo dos Testes , Gravidez , Estudos Retrospectivos , Medição de Risco , Ultrassonografia Doppler , Ultrassonografia Pré-Natal/métodos , Artéria Uterina/diagnóstico por imagem , Artéria Uterina/patologiaRESUMO
Screening for human papillomavirus (HPV) integration into host cell chromosomes typically requires large amounts of time and reagents. We developed a rapid and sensitive assay based on exonuclease V (ExoV) and quantitative polymerase chain reaction (qPCR) to determine HPV genome configurations in cell lines and tissues. We established the assay using genomic DNA from cell lines known to harbor integrated or episomal HPV16. DNA was incubated with ExoV, which is specific for linear DNA, and the DNA fraction resistant to digestion was measured by qPCR. The percent of DNA resistant to ExoV digestion was calculated relative to undigested DNA for determination of episomal or integrated HPV16. The ExoV assay was accurate, capable of distinguishing episomal from integrated HPV16 in cell lines and tissues. Future applications of the ExoV assay may include screening of HPV genome configurations in the progression of HPV-associated cancers.
Assuntos
DNA Viral/análise , Exodesoxirribonuclease V/metabolismo , Papillomavirus Humano 16/genética , Plasmídeos , Provírus/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Integração Viral , Células Cultivadas , DNA Viral/genética , Papillomavirus Humano 16/crescimento & desenvolvimento , HumanosRESUMO
OBJECTIVE: To calculate the cost-effectiveness of implementing PlGF testing alongside a clinical management algorithm in maternity services in the UK, compared with current standard care. DESIGN: Cost-effectiveness analysis. SETTING: Eleven maternity units participating in the PARROT stepped-wedge cluster-randomised controlled trial. POPULATION: Women presenting with suspected pre-eclampsia between 20+0 and 36+6 weeks' gestation. METHODS: Monte Carlo simulation utilising resource use data and maternal adverse outcomes. MAIN OUTCOME MEASURES: Cost per maternal adverse outcome prevented. RESULTS: Clinical care with PlGF testing costs less than current standard practice and resulted in fewer maternal adverse outcomes. There is a total cost-saving of UK£149 per patient tested, when including the cost of the test. This represents a potential cost-saving of UK£2,891,196 each year across the NHS in England. CONCLUSIONS: Clinical care with PlGF testing is associated with the potential for cost-savings per participant tested when compared with current practice via a reduction in outpatient attendances, and improves maternal outcomes. This economic analysis supports a role for implementation of PlGF testing in antenatal services for the assessment of women with suspected pre-eclampsia. TWEETABLE ABSTRACT: Placental growth factor testing for suspected pre-eclampsia is cost-saving and improves maternal outcomes.
Assuntos
Técnicas de Diagnóstico Obstétrico e Ginecológico/economia , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Complicações na Gravidez/sangue , Complicações na Gravidez/diagnóstico , Adulto , Biomarcadores/sangue , Análise por Conglomerados , Análise Custo-Benefício , Feminino , Idade Gestacional , Humanos , Modelos Econômicos , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações na Gravidez/epidemiologia , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: Raised vascular function measures are associated with adverse maternal and perinatal outcomes in low-risk pregnancy. This study aimed to evaluate the association between longitudinal vascular function parameters and adverse outcome in pregnant women with chronic hypertension, and to assess whether these measures vary according to baseline parameters such as black ethnicity. METHODS: This was a nested cohort study of women with chronic hypertension and a singleton pregnancy recruited to the PANDA (Pregnancy And chronic hypertension: NifeDipine vs lAbetalol as antihypertensive treatment) study at one of three UK maternity units. Women had serial pulse-wave analyses performed using the Arteriograph®, while in a sitting position, from 12 weeks' gestation onwards. Statistical analysis was performed using random-effects logistic regression models. Longitudinal vascular parameters were compared between women who developed superimposed pre-eclampsia (SPE) and those who did not, between women who delivered a small-for-gestational-age (SGA) infant (birth weight < 10th centile) and those who delivered an infant with birth weight ≥ 10th centile and between women of black ethnicity and those of non-black ethnicity. RESULTS: The cohort included 97 women with chronic hypertension and a singleton pregnancy, of whom 90% (n = 87) were randomized to antihypertensive treatment and 57% (n = 55) were of black ethnicity, with up to six (mean, three) longitudinal vascular function assessments. SPE was diagnosed in 18% (n = 17) of women and 30% (n = 29) of infants were SGA. In women who developed subsequent SPE, compared with those who did not, mean brachial systolic blood pressure (SBP) (148 mmHg vs 139 mmHg; P = 0.002), mean diastolic blood pressure (DBP) (87 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (139 mmHg vs 128 mmHg; P = 0.001) and mean augmentation index (AIx-75) (29% vs 22%; P = 0.01) were significantly higher across gestation. In women who delivered a SGA infant compared to those who delivered an infant with birth weight ≥ 10th centile, mean brachial SBP (146 mmHg vs 138 mmHg; P = 0.001), mean DBP (86 mmHg vs 82 mmHg; P = 0.01), mean central aortic pressure (137 mmHg vs 127 mmHg; P < 0.0001) and mean pulse-wave velocity (9.1 m/s vs 8.5 m/s; P = 0.02) were higher across gestation. No longitudinal differences were found in vascular function parameters in women of black ethnicity compared with those of non-black ethnicity. CONCLUSION: There were persistent differences in vascular function parameters and brachial blood pressure throughout pregnancy in women with chronic hypertension who later developed adverse maternal or perinatal outcome. Further investigation into the possible clinical use of these findings is warranted. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
População Negra/estatística & dados numéricos , Pressão Sanguínea , Hipertensão/fisiopatologia , Complicações Cardiovasculares na Gravidez/fisiopatologia , Análise de Onda de Pulso/estatística & dados numéricos , Adulto , Anti-Hipertensivos/uso terapêutico , Peso ao Nascer , Doença Crônica , Estudos de Coortes , Estudos de Viabilidade , Feminino , Idade Gestacional , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etnologia , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Labetalol/uso terapêutico , Estudos Longitudinais , Nifedipino/uso terapêutico , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/etnologia , Pré-Eclâmpsia/fisiopatologia , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/etnologia , Resultado da Gravidez/etnologia , Análise de Regressão , Resultado do TratamentoRESUMO
OBJECTIVE: To assess the impact of maternal ethnicity on the risk of adverse perinatal outcome in pregnant women with chronic hypertension. METHODS: Demographic and delivery data were collated of women with chronic hypertension and singleton pregnancy who delivered at one of three UK obstetric units between 2000 and 2014. Multivariable logistic regression models were used to calculate risk ratios (RR), according to ethnic group, for adverse perinatal outcome, adjusted for other maternal characteristics including age, parity, body mass index, smoking status, deprivation index and year of delivery. The impact of maternal ethnicity on birth-weight centile calculation was investigated by comparing the birth-weight centile chart customized for ethnicity (Gestation Related Optimal Weight; GROW) with a birth-weight centile calculator that does not adjust for that factor (INTERGROWTH-21st ). RESULTS: The study cohort included 4481 pregnancies (4045 women) with chronic hypertension. Women of white ethnicity accounted for 47% (n = 2122) of the cohort and 36% (n = 1601) were of black, 8.5% (n = 379) of Asian and 8.5% (n = 379) of other ethnicity. The overall incidence of stillbirth was 1.6%, that of preterm birth < 37 weeks was 16% and that of fetal growth restriction (birth weight < 3rd centile) was 11%. Black women, compared with white women, had the highest risk for all adverse perinatal outcomes, with stillbirth occurring in 3.1% vs 0.6% of pregnancies (adjusted RR (aRR), 5.56 (95% CI, 2.79-11.09)), preterm birth < 37 weeks in 21% vs 11% (aRR, 1.70 (95% CI, 1.43-2.01)) and birth weight < 3rd centile in 15% vs 7.4% (aRR, 2.07 (95% CI, 1.71-2.51)). Asian women, compared with white women, were also at increased risk of adverse perinatal outcome, with stillbirth occurring in 1.6% vs 0.6% (aRR, 3.03 (95% CI, 1.11-8.28)), preterm birth < 37 weeks in 20% vs 11% (aRR, 1.82 (95% CI, 1.41-2.35)) and birth weight < 3rd centile in 12% vs 7.4% (aRR, 1.69 (95% CI, 1.24-2.30)). The sensitivity and specificity for prediction of infants requiring neonatal unit admission were 40% and 93%, respectively, for those with birth weight < 3rd centile according to GROW charts, compared with 16% and 96%, respectively, for those with birth weight < 3rd centile according to INTERGROWTH-21st charts. CONCLUSIONS: Black ethnicity, compared with white, is associated with the greatest risk of adverse perinatal outcome in women with chronic hypertension, even after adjusting for other maternal characteristics. Women of Asian ethnicity are also at increased risk, but to a lesser extent. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.
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Hipertensão/complicações , Resultado da Gravidez/epidemiologia , Natimorto/epidemiologia , Adulto , Peso ao Nascer , Doença Crônica , Etnicidade , Feminino , Morte Fetal , Retardo do Crescimento Fetal/epidemiologia , Humanos , Hipertensão/diagnóstico , Hipertensão/etnologia , Hipertensão/fisiopatologia , Incidência , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido Pequeno para a Idade Gestacional , Paridade , Gravidez , Reino Unido/epidemiologiaRESUMO
Epstein-Barr virus (EBV) is implicated in the pathogenesis of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OSCC). EBV-associated cancers harbor a latent EBV infection characterized by a lack of viral replication and the expression of viral oncogenes. Cellular changes promoted by HPV are comparable to those shown to facilitate EBV latency, though whether HPV-positive cells support a latent EBV infection has not been demonstrated. Using a model of direct EBV infection into HPV16-immortalized tonsillar cells grown in organotypic raft culture, we showed robust EBV replication in HPV-negative rafts but little to no replication in HPV-immortalized rafts. The reduced EBV replication was independent of immortalization, as human telomerase-immortalized normal oral keratinocytes supported robust EBV replication. Furthermore, we observed reduced EBV lytic gene expression and increased expression of EBER1, a noncoding RNA highly expressed in latently infected cells, in the presence of HPV. The use of human foreskin keratinocyte rafts expressing the HPV16 E6 and/or E7 oncogene(s) (HPV E6 and E7 rafts) showed that E7 was sufficient to reduce EBV replication. EBV replication is dependent upon epithelial differentiation and the differentiation-dependent expression of the transcription factors KLF4 and PRDM1. While KLF4 and PRDM1 levels were unaltered, the expression levels of KLF4 transcriptional targets, including late differentiation markers, were reduced in HPV E6 and E7 rafts compared to their levels in parental rafts. However, the HPV E7-mediated block in EBV replication correlated with delayed expression of early differentiation markers. Overall, this study reveals an HPV16-mediated block in EBV replication, through E7, that may facilitate EBV latency and long-term persistence in the tumor context.IMPORTANCE Using a model examining the establishment of EBV infection in HPV-immortalized tissues, we showed an HPV-induced interruption of the normal EBV life cycle reminiscent of a latent EBV infection. Our data support the notion that a persistent EBV epithelial infection depends upon preexisting cellular alterations and suggest the ability of HPV to promote such changes. More importantly, these findings introduce a model for how EBV coinfection may influence HPV-positive (HPV-pos) OSCC pathogenesis. Latently EBV-infected epithelial cells, as well as other EBV-associated head-and-neck carcinomas, exhibit oncogenic phenotypes commonly seen in HPV-pos OSCC. Therefore, an HPV-induced shift in the EBV life cycle toward latency would not only facilitate EBV persistence but also provide additional viral oncogene expression, which can contribute to the rapid progression of HPV-pos OSCC. These findings provide a step toward defining a role for EBV as a cofactor in HPV-positive oropharyngeal tumors.
Assuntos
Células Epiteliais/virologia , Herpesvirus Humano 4/fisiologia , Papillomavirus Humano 16/metabolismo , Queratinócitos/citologia , Proteínas Oncogênicas Virais/metabolismo , Proteínas E7 de Papillomavirus/metabolismo , Proteínas Repressoras/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Células Epiteliais/citologia , Prepúcio do Pênis/citologia , Papillomavirus Humano 16/fisiologia , Humanos , Queratinócitos/virologia , Fator 4 Semelhante a Kruppel , Masculino , Camundongos , Células NIH 3T3 , Tonsila Palatina/citologia , Tonsila Palatina/virologia , Latência Viral , Replicação ViralRESUMO
BACKGROUND: Gunshot injuries from interpersonal violence are a major cause of mortality. In South Africa (SA), the Firearms Control Act of 2000 sought to address firearm violence by removing illegally owned firearms from circulation, stricter regulation of legally owned firearms, and stricter licensing requirements. Over the last few years, varied implementation of the Act and police corruption have increased firearm availability. OBJECTIVES: To investigate whether changes in firearm availability in SA were associated with changes in firearm homicide rates. METHODS: This was a retrospective time trend study (1994 - 2013) using postmortem data. Time trends of firearm and non-firearm homicide rates were analysed with generalised linear models. Distinct time periods for temporal trends were assigned based on a priori assumptions regarding changes in the availability of firearms. RESULTS: Firearm and non-firearm homicide rates adjusted for age, sex and race exhibited different temporal trends. Non-firearm homicide rates either decreased or remained stable over the entire period. Firearm homicide increased at 13% annually from 1994 through 2000, and decreased by 15% from 2003 through 2006, corresponding with changes in firearm availability in 2001, 2003, 2007 and 2011. A 21% annual increase in firearm homicide after 2010 coincided with police fast-tracking new firearm licence applications. Cape Town's coloured population experienced a significantly greater increase than other population groups following additional exposure to illegal firearms from 2007. CONCLUSIONS: The strong association between firearm availability and homicide, and the reversal of a decreasing firearm homicide trend during a period of lax enforcement, provide further support for the association between reduced firearm homicide and stricter regulation.
RESUMO
The specific consequences of hyperglycaemia on placental metabolism and function are incompletely understood but likely contribute to poor pregnancy outcomes associated with diabetes mellitus (DM). This study aimed to identify the functional biochemical pathways perturbed by placental exposure to high glucose levels through integrative analysis of the trophoblast transcriptome and metabolome. The human trophoblast cell line, BeWo, was cultured in 5 or 25 mM glucose, as a model of the placenta in DM. Transcriptomic analysis using microarrays, demonstrated 5632 differentially expressed gene transcripts (≥± 1.3 fold change (FC)) following exposure to high glucose. These genes were used to generate interactome models of transcript response using BioGRID (non-inferred network: 2500 nodes (genes) and 10541 protein-protein interactions). Ultra performance-liquid chromatography-mass spectrometry (MS) and gas chromatography-MS analysis of intracellular extracts and culture medium were used to assess the response of metabolite profiles to high glucose concentration. The interactions of altered genes and metabolites were assessed using the MetScape interactome database, resulting in an integrated model of systemic transcriptome (2969 genes) and metabolome (41 metabolites) response within placental cells exposed to high glucose. The functional pathways which demonstrated significant change in response to high glucose included fatty acid ß-oxidation, phospholipid metabolism and phosphatidylinositol phosphate signalling.
Assuntos
Glucose/metabolismo , Hiperglicemia/metabolismo , Metaboloma , Placenta/metabolismo , Transcriptoma , Animais , Linhagem Celular , Complicações do Diabetes/genética , Complicações do Diabetes/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Hiperglicemia/genética , Metabolismo dos Lipídeos , Camundongos , Gravidez , Complicações na Gravidez/genética , Complicações na Gravidez/metabolismo , Trofoblastos/metabolismoRESUMO
OBJECTIVE: To evaluate the use of plasma Placental Growth Factor (PlGF), recommended by the recent NICE guidance, in women with suspected pre-eclampsia (PE) and/or fetal growth restriction (FGR). STUDY DESIGN: Non-randomised prospective clinical evaluation study in high-risk antenatal clinics in a tertiary maternity unit. METHODS: PlGF testing was performed in addition to routine clinical assessment in 260 women >20â¯weeks' gestation with chronic disease (hypertension, renal disease⯱â¯diabetes) with a change in maternal condition or in women with suspected FGR to determine the impact on clinical management. Results were revealed and standardised care pathways followed. MAIN OUTCOME MEASURES: Outcome of pregnancies with a low PlGF (<12â¯pg/ml and 13-100â¯pg/ml), impact on clinical service and the diagnostic accuracy of alternative PlGF cut-offs. RESULTS: 206/260 (79.2%) women had an adverse outcome (PE/birthweightâ¯<â¯10th centile/preterm birth). In our cohort, a low PlGF (<12â¯pg/ml) was associated with a shorter test-birth interval and universally (100% PPV) with an adverse pregnancy outcome, although 29/61 (47.5%) of women with PlGFâ¯<â¯12â¯pg/ml continued their pregnancy >14â¯days. The PlGF result altered clinical management (surveillance or timing of birth) in 196/260 (75.4%) cases. Alternative PlGF thresholds did not significantly improve diagnostic performance. CONCLUSIONS: Our evaluation confirms the value of PlGF as a diagnostic tool for placental dysfunction. However, low PlGF in isolation should not trigger iatrogenic delivery. Further research linking placental pathology, maternal disease and maternal PlGF levels is urgently needed before this test can be implemented in routine clinical practice.
Assuntos
Retardo do Crescimento Fetal/sangue , Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/sangue , Resultado da Gravidez/epidemiologia , Biomarcadores/sangue , Feminino , Retardo do Crescimento Fetal/diagnóstico , Humanos , Placenta/fisiopatologia , Pré-Eclâmpsia/diagnóstico , Gravidez , Nascimento Prematuro/epidemiologia , Cuidado Pré-Natal/métodos , Cuidado Pré-Natal/estatística & dados numéricos , Estudos Prospectivos , Índice de Gravidade de DoençaRESUMO
AIM: To compare the blood pressure (BP) lowering effects of labetalol and nifedipine modified release (MR) in hypertensive pregnant women. We also investigated the effect on the heart rate (HR) and determined the proportion of time spent in target. METHODS: This was an exploratory study. Women with chronic hypertension taking either labetalol or nifedipine were offered 24-h ambulatory blood pressure monitoring (ABPM). Sleep, wake and drug ingestion times were self-reported. An indirect response model was used to analyse the systolic BP (SBP), diastolic BP (DBP) and HR time-series; the effect of gestation and type of drug was evaluated. RESULTS: Forty-eight women were recruited: 24 in each group. There was no difference in clinical characteristics. In women taking nifedipine there was a positive association between the dose of nifedipine and pre-dose BP pâ¯=â¯.002, this was not present in the labetalol group. There was a difference between the drug effects on both the SBP and DBP time-series (pâ¯=â¯.014). In comparison to labetalol, there was less variation in day time BP in those women prescribed nifedipine. Women on labetalol spent a larger proportion of time with their DBP below target (<80â¯mmHg). The HR dynamics were qualitatively different, a stimulatory effect was found with nifedipine compared to an inhibitory effect with labetalol. CONCLUSION: There are significant and important differences between the BP lowering effects of nifedipine and labetalol. A large randomised control trial is required to investigate the relationship between BP variability and time in target on pregnancy outcomes.
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Antagonistas Adrenérgicos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/uso terapêutico , Hipertensão Induzida pela Gravidez/tratamento farmacológico , Labetalol/uso terapêutico , Nifedipino/uso terapêutico , Vasodilatadores/uso terapêutico , Antagonistas Adrenérgicos/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Doença Crônica , Preparações de Ação Retardada , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/fisiopatologia , Labetalol/efeitos adversos , Nifedipino/efeitos adversos , Gravidez , Fatores de Tempo , Resultado do Tratamento , Vasodilatadores/efeitos adversosRESUMO
AIMS: To determine the performance of a fasting glucose sample compared with a full oral glucose tolerance test for the detection of glucose abnormalities in a diverse ethnic population after gestational diabetes. METHODS: Oral glucose tolerance test results for women attending post-natal testing over a 10-year (2003-2013) period at St Mary's Hospital, Manchester, UK were reviewed. Demographic data were also extracted from the hospital maternity database. RESULTS: The average attendance for a post-natal oral glucose tolerance test was approximately 45% over the study period. The prevalence of diabetes was 4.8% (30/629), with a higher rate in women of Asian ethnicity compared with other groups (6.6% vs. 3.5%). The sensitivity for a fasting plasma glucose of ≥ 6.1 mmol/l was 90% (95% CI 74.4-96.5%) for the detection of diabetes and 61% (49.1-71.5%) for the detection of diabetes and/or impaired glucose tolerance, with specificities of 91% (88.8-93.3%) and 93% (91.0-95.2%), respectively. The positive and negative likelihood ratios for diabetes and impaired glucose tolerance were 10.4 (7.8-13.8), 0.11 (0.03-0.32) and 9.2 (6.4-13.3), 0.42 (0.31-0.56), respectively. A fasting plasma glucose threshold of 5.6 mmol/l improved the sensitivity for impaired glucose tolerance (from 61% to 77%), but made no difference to the sensitivity for diabetes. CONCLUSIONS: The current study has demonstrated that detection of diabetes after gestational diabetes, in an ethnically diverse population using a fasting plasma glucose only, was approximately 90%. Compliance with post-natal screening might improve if women attended for a fasting plasma glucose only; this strategy would identify approximately 90% of cases of diabetes and 40% of cases of impaired glucose tolerance.
Assuntos
Diabetes Gestacional/sangue , Teste de Tolerância a Glucose , Cuidado Pós-Natal/métodos , Adulto , Diabetes Gestacional/epidemiologia , Jejum/sangue , Feminino , Teste de Tolerância a Glucose/métodos , Hemoglobinas Glicadas/metabolismo , Humanos , Recém-Nascido , Gravidez , Prevalência , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Reino Unido/epidemiologiaRESUMO
OBJECTIVES: To assess the performance of clinical risk factors, uterine artery Doppler and angiogenic markers to predict preterm pre-eclampsia in nulliparous women. DESIGN: Predictive test accuracy study. SETTING: Prospective multicentre cohort study Screening for Pregnancy Endpoints (SCOPE). METHODS: Low-risk nulliparous women with a singleton pregnancy were recruited. Clinical risk factor data were obtained and plasma placental growth factor (PlGF), soluble endoglin and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured at 14-16 weeks of gestation. Prediction models were developed using multivariable stepwise logistic regression. MAIN OUTCOME MEASURE: Preterm pre-eclampsia (delivered before 37(+0) weeks of gestation). RESULTS: Of the 3529 women recruited, 187 (5.3%) developed pre-eclampsia of whom 47 (1.3%) delivered preterm. Controls (n = 188) were randomly selected from women without preterm pre-eclampsia and included women who developed other pregnancy complications. An area under a receiver operating characteristic curve (AUC) of 0.76 (95% CI 0.67-0.84) was observed using previously reported clinical risk variables. The AUC improved following the addition of PlGF measured at 14-16 weeks (0.84; 95% CI 0.77-0.91), but no further improvement was observed with the addition of uterine artery Doppler or the other angiogenic markers. A sensitivity of 45% (95% CI 0.31-0.59) (5% false-positive rate) and post-test probability of 11% (95% CI 9-13) were observed using clinical risk variables and PlGF measurement. CONCLUSIONS: Addition of plasma PlGF at 14-16 weeks of gestation to clinical risk assessment improved the identification of nulliparous women at increased risk of developing preterm pre-eclampsia, but the performance is not sufficient to warrant introduction as a clinical screening test. These findings are marker dependent, not assay dependent; additional markers are needed to achieve clinical utility.
Assuntos
Antígenos CD/sangue , Pré-Eclâmpsia/sangue , Pré-Eclâmpsia/diagnóstico , Proteínas da Gravidez/sangue , Receptores de Superfície Celular/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Área Sob a Curva , Biomarcadores/sangue , Endoglina , Feminino , Humanos , Paridade , Fator de Crescimento Placentário , Pré-Eclâmpsia/diagnóstico por imagem , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez/sangue , Segundo Trimestre da Gravidez/sangue , Nascimento Prematuro/sangue , Curva ROC , Fatores de Risco , Ultrassonografia Doppler , Artéria Uterina/diagnóstico por imagem , Adulto JovemRESUMO
OBJECTIVES: This study assessed whether the quality of the available road traffic injury (RTI) data was sufficient for determining the burden of RTIs in the Western Cape Province and for implementing and monitoring road safety interventions. METHODOLOGY: Underreporting was assessed by comparing data reported by the South African Police Services (SAPS) in 2008 with data from 18 provincial mortuaries. Completeness of the driver death subset of all RTIs was assessed using the capture-recapture method. RESULTS: The mortuary and police data sets comprised 1696 and 860 fatalities respectively for the year 2008. The corresponding provincial road traffic mortality rates were as follows: 32.2 deaths/100,000 population per year (95% confidence interval [CI]: 30.7-33.8) and 16.3 deaths/100,000 population per year (95% CI: 15.3-17.5). The police data set contained 820,960 crashes, involving 196,889 persons, indicating substantial duplication of crash events. There were varying proportions of missing data for demographic and other identifying variables, with age missing in nearly half of the cases in the police data set. The estimated total number of driver deaths/year was 588.6 (95% CI: 544.4-632.8), yielding estimated completeness of the mortuary and police data sets of 57.6 and 46.4 percent separately and 77.3 percent combined. CONCLUSION: This study found extensive data quality problems, including missing data, duplication, and significant underreporting of traffic injury deaths in the police data. Not all assumptions underlying the use of capture-recapture method were met in this study; hence, the estimates provided by this analysis should be interpreted with caution. There is a need to address the problems highlighted by this study in order to improve data utility for informing road safety policies. Supplemental materials are available for this article. Go to the publisher's online edition of Traffic Injury Prevention to view the supplemental file.
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Acidentes de Trânsito/mortalidade , Práticas Mortuárias , Polícia , Registros/normas , Ferimentos e Lesões/mortalidade , Acidentes de Trânsito/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , África do Sul/epidemiologia , Ferimentos e Lesões/prevenção & controle , Adulto JovemRESUMO
BACKGROUND: Current driver mortality estimates do not consider the great differences in exposure across the population, giving a false impression that driver deaths are lowest in the youngest age group. Interventions to reduce risk among the younger age group include graduated driver licensing (GDL) - a three-phase licensing system for novice drivers consisting of a learner's permit, a provisional license, and a full license. OBJECTIVES: We calculated driver fatality rates per 10 000 registered drivers in each age group and assessed the need for stricter licensing conditions for novice and younger drivers. METHODS: Age-specific driver mortality rates were calculated using Western Cape Province 2008 mortuary data. The total number of licensed drivers in each age group served as the denominator. Incidence rate ratios were calculated using the age group of 65 - 79 years as the reference. Chi-square test of trend on incidence rate ratios for the age groups was done. Statistical significance was set as p<0.05. RESULTS: There were 339 driver deaths; mean age was 39.4±13.8 years, and males accounted for 80% of the deaths. Age-specific driver mortality rates were highest in the youngest age group (15 - 19 years). There was a significant progressive decrease (except for the age group 45 - 49 years) in the risk of death from road traffic injuries with increasing age compared with the age group ≥ 65 years (chi2 for trend p<0.0001). CONCLUSION; This study showed a relationship between driver's mortality risk and younger age, and underscores the need for introduction of a GDL programme in South Africa.
Assuntos
Acidentes de Trânsito/mortalidade , Condução de Veículo , Licenciamento , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação das Necessidades , Fatores de Risco , Fatores Sexuais , África do Sul/epidemiologia , Adulto JovemRESUMO
Diabetes mellitus is associated with abnormalities in placental structure and function and significant pregnancy complications. In vitro studies to investigate the effect of hyperglycaemia on trophoblast structure and function require an accurate, inexpensive and reliable assay to monitor the concentration of glucose in culture medium. We have modified and validated an existing protocol for use with a 96-well microplate. This provides a specific, high-throughput assay which accurately measures culture media glucose concentrations between 7 and 30 mM, without spectral interferences by phenol red or sera. Use of this assay revealed that the concentration of glucose in BeWo cell cultures remains stable for 48 h. In contrast placental explants rapidly consume glucose thus the concentration in culture media significantly decreases over 12 h necessitating more frequent replenishment in order to maintain the desired concentration. We therefore advise researchers to monitor glucose concentrations in in vitro investigations modelling the effect of diabetes mellitus on placental structure and function.
Assuntos
Glucose/metabolismo , Placenta/metabolismo , Trofoblastos/metabolismo , Adulto , Transporte Biológico , Linhagem Celular , Células Cultivadas , Meios de Cultivo Condicionados/análise , Meios de Cultura Livres de Soro/análise , Feminino , Glucose/análise , Glucose Oxidase/metabolismo , Peroxidase do Rábano Silvestre/metabolismo , Humanos , Hiperglicemia/metabolismo , Indicadores e Reagentes/química , Concentração Osmolar , Gravidez , Espectrofotometria , Fatores de Tempo , Técnicas de Cultura de Tecidos , Trofoblastos/citologiaRESUMO
OBJECTIVE: To determine whether the rate of caesarean section was increased in women undergoing fetal blood sampling (FBS) in early labour. DESIGN: Retrospective study. SETTING: Secondary and tertiary obstetric units in the UK. POPULATION: A cohort of 381 women undergoing FBS. METHODS: Data relating to demographics, labour and delivery characteristics, and neonatal outcomes were collected on women undergoing FBS in labour. Odds ratios (ORs) for caesarean section compared with vaginal delivery for women who had their first FBS in early labour (≤ 3 cm cervical dilatation) and for women who required multiple samples were calculated. MAIN OUTCOME MEASURES: Mode of delivery. RESULTS: Forty-eight percent of women who required their first FBS at a cervical dilatation of ≤ 3 cm achieved a vaginal delivery; these women were at modestly increased risk of caesarean section (adjusted OR 1.80; 95% CI 1.04-3.13) compared with women who had their first FBS at a cervical dilatation of ≥ 4 cm. The odds ratio for caesarean section in women who required two or more FBS was 1.71 (95% CI 1.37-2.13) compared with those requiring a single sample. There were no differences in instrumental delivery. Infants undergoing three or more FBS were more likely to be admitted to a neonatal intensive care unit (NICU; OR 2.69; 95% CI 1.09-6.64), although this was not associated with increased acidaemia. CONCLUSIONS: Women who require FBS in early labour or multiple FBS are at a modestly increased risk of caesarean section compared with those in established labour. When contemplating FBS at ≤ 3-cm cervical dilatation, practitioners should not be put off by the perceived low chance of vaginal delivery, but repeating FBS on more than three occasions should be considered carefully.