Maternal cardiac function in women at high risk for pre-eclampsia treated with 150 mg aspirin or placebo: an observational study.

OBJECTIVE: To compare maternal haemodynamics in women at low and high risk for preterm pre-eclampsia (PE), and between those at high risk who are randomised to aspirin or placebo. DESIGN: Prospective, longitudinal observational study. SETTING: Maternity units in six UK hospitals. POPULATION: Women participating in the Aspirin for Prevention of Preterm Pre-eclampsia (ASPRE) trial. The population comprised three groups of women: low risk for preterm PE (n = 1362), high risk for preterm PE treated with aspirin (n = 208) and high risk for preterm PE on placebo (n = 220). METHODS: Women had four visits during pregnancy: 11-14, 19-24, 30-34, and 35-37 weeks' gestation. Blood pressure was measured with a device validated for pregnancy, and PE and maternal haemodynamics were assessed with a bioreactance monitor at each visit. A multilevel linear mixed-effects analysis was performed to examine longitudinal changes of maternal haemodynamic variables, controlling for demographic characteristics, past medical history and medication use. MAIN OUTCOME MEASURES: Longitudinal changes of cardiac output (CO), mean arterial pressure (MAP), and peripheral vascular resistance (PVR). RESULTS: The low-risk group demonstrated the expected changes with an increase in CO and reduction in MAP and PVR, with a quadratic change across gestation. In contrast, the high-risk groups had a declining CO, and higher MAP and PVR during pregnancy. The administration of aspirin did not appear to affect maternal haemodynamics. CONCLUSIONS: Women screened as high risk for preterm PE have a pathological cardiac adaptation to pregnancy and the prophylactic use of aspirin (150 mg oral daily from the first trimester) in this group may not alter this haemodynamic profile. TWEETABLE ABSTRACT: In women at high risk of pre-eclampsia, prophylactic use of aspirin may not alter the impaired maternal cardiac adaptation.

Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

Effect of race on longitudinal central hemodynamics in pregnancy.

OBJECTIVE: To compare central hemodynamics between white, black and Asian women in pregnancy. METHODS: This was a prospective, longitudinal study of maternal central hemodynamics in white, black and Asian women with a singleton pregnancy, assessed using a bioreactance method at 11 + 0 to 13 + 6, 19 + 0 to 24 + 0, 30 + 0 to 34 + 0 and 35 + 0 to 37 + 0 weeks' gestation. At each visit, cardiac output (CO), stroke volume (SV), heart rate (HR), peripheral vascular resistance (PVR) and mean arterial pressure were recorded. Multilevel linear mixed-effects analysis was performed to compare the repeated measures of the cardiac variables between white, black and Asian women, controlling for maternal characteristics, medical history and medication use. RESULTS: The study population included 1165 white, 247 black and 116 Asian women. CO increased with gestational age to a peak at 32 weeks and then decreased; the highest CO was observed in white women and the lowest in Asian women. SV initially increased after the first visit but subsequently declined with gestational age in white women, decreased with gestational age in black women and remained static in Asian women. In all three study groups, HR increased with gestational age until 32 weeks and then remained constant; HR was highest in black women and lowest in white women. PVR showed a reversed pattern to that of CO; the highest values were in Asian women and the lowest in white women. The least favorable hemodynamic profile, which was observed in black and Asian women, was reflected in higher rates of a small-for-gestational-age infant. CONCLUSIONS: There are race-specific differences in maternal cardiac adaptation to pregnancy. White women have the most favorable cardiac adaptation by increasing SV and HR, achieving the highest CO and lowest PVR. In contrast, black and Asian women have lower CO and higher PVR than do white women, with CO increasing through a rise in HR due to declining or static SV. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Maternal hemodynamics in screen-positive and screen-negative women of the ASPRE trial.

OBJECTIVE: To compare maternal hemodynamics and perinatal outcome, in pregnancies that do not develop pre-eclampsia (PE) or deliver a small-for-gestational-age (SGA) neonate, between those identified at 11-13 weeks' gestation as being screen positive or negative for preterm PE, by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, serum placental growth factor and pregnancy associated plasma protein-A. METHODS: This was a prospective longitudinal cohort study of maternal cardiovascular function, assessed using a bioreactance method, in women undergoing first-trimester screening for PE. Maternal hemodynamics and perinatal outcome were compared between screen-positive and screen-negative women who did not have a medical comorbidity, did not develop PE or pregnancy-induced hypertension and delivered at term a live neonate with birth weight between the 5th and 95th percentiles. A multilevel linear mixed-effects model was used to compare the repeated measures of cardiac variables, controlling for maternal characteristics. RESULTS: The screen-negative group (n = 926) had normal cardiac function changes across gestation, whereas the screen-positive group (n = 170) demonstrated static or reduced cardiac output and stroke volume and higher mean arterial pressure and peripheral vascular resistance with advancing gestation. In the screen-positive group, compared with screen-negative women, birth-weight Z-score was shifted toward lower values, with prevalence of delivery of a neonate below the 35th , 30th or 25th percentile being about 70% higher, and the rate of operative delivery for fetal distress in labor also being higher. CONCLUSION: Women who were screen positive for impaired placentation, even though they did not develop PE or deliver a SGA neonate, had pathological cardiac adaptation in pregnancy and increased risk of adverse perinatal outcome. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Impact of a nutrition and physical activity intervention (ENRICH: Exercise and Nutrition Routine Improving Cancer Health) on health behaviors of cancer survivors and carers: a pragmatic randomized controlled trial.

BACKGROUND: Physical activity and consuming a healthy diet have clear benefits to the physical and psychosocial health of cancer survivors, with guidelines recognising the importance of these behaviors for cancer survivors. Interventions to promote physical activity and improve dietary behaviors among cancer survivors and carers are needed. The aim of this study was to determine the effects of a group-based, face-to-face multiple health behavior change intervention on behavioral outcomes among cancer survivors of mixed diagnoses and carers. METHODS: The Exercise and Nutrition Routine Improving Cancer Health (ENRICH) intervention was evaluated using a two-group pragmatic randomized controlled trial. Cancer survivors and carers (n = 174) were randomly allocated to the face-to-face, group-based intervention (six, theory-based two-hour sessions delivered over 8 weeks targeting healthy eating and physical activity [PA]) or wait-list control (after completion of 20-week data collection). Assessment of the primary outcome (pedometer-assessed mean daily step counts) and secondary outcomes (diet and alcohol intake [Food Frequency Questionnaire], self-reported PA, weight, body mass index, and waist circumference) were assessed at baseline, 8-and 20-weeks. RESULTS: There was a significant difference between the change over time in the intervention group and the control group. At 20 weeks, the intervention group had increased by 478 steps, and the control group had decreased by 1282 steps; this represented an adjusted mean difference of 1761 steps (184 to 3337; P = 0.0028). Significant intervention effects for secondary outcomes, included a half serving increase in vegetable intake (difference 39 g/day; 95 % CI: 12 to 67; P = 0.02), weight loss (kg) (difference -1.5 kg; 95 % CI, -2.6 to -0.3; P = 0.014) and change in body mass index (kg/m(2)) (difference -0.55 kg/m(2); 95 % CI, -0.97 to -0.13; P = 0.012). No significant intervention effects were found for self-reported PA, total sitting time, waist circumference, fruit, energy, fibre, alcohol, meat, or fat consumption. CONCLUSIONS: The ENRICH intervention was effective for improving PA, weight, body mass index, and vegetable consumption even with the inclusion of multiple cancer types and carers. As an example of successful research translation, the Cancer Council NSW has subsequently adopted ENRICH as a state-wide program. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Register identifier: ANZCTRN1260901086257.

Smoky homes: gender, socioeconomic and housing disparities in second hand tobacco smoke (SHS) exposure in a large population-based Australian cohort.

OBJECTIVE: Although research suggests that socioeconomic status (SES) will be related to housing type with regard to second-hand smoke (SHS) exposure, there has been no comprehensive examination of these relationships. This study aimed to explore associations between SHS exposure a) at home and b) at other places, and a number of SES, housing, and health factors. METHOD: Data were drawn from the 45 and Up Study, a large cohort study with 266,848 adults in New South Wales, Australia, of which 160,824 participants aged 45-65years were included in this study. Associations between socio-demographic characteristics, smoking status, housing-type, SES, and exposure to SHS were explored initially using Chi-square tests. Ordinal logistic models were created with increasing exposure to SHS at home and at other places. RESULTS: When measuring SHS exposure at home, being female (odds ratio (OR)=1.2, 95% confidence interval (CI)=1.2, 1.3); being of lower age (45-49years vs 60-64years, OR=1.4, 95%CI=1.3, 1.5), being a current smoker of over 20 cigarettes per day (vs never smoked, OR=10.2, 95%CI=9.4,11); living in other types of dwelling compared to living at home (OR=1.3, 95%CI=1.1, 1.4), living with a partner (vs being single OR=2.3, 95%CI=2.1, 2.5), and low SES measures were associated with increased exposure. Increasing SHS exposure at other places was also related to low SES measures, however unlike SHS exposure at home, SHS exposure at other places was associated with being male (OR=1.5, 95%CI=1.5, 1.6); and greater paid hours of work (OR=1.3, 95%CI=1.2, 1.3). CONCLUSION: Improved monitoring of SHS exposure in high risk environments is required. Tailoring SHS messages to environments may also be required, for example to women living in units, apartments and mobile homes and males in lower income workplaces.

Administration of chemotherapy with palliative intent in the last 30 days of life: the balance between palliation and chemotherapy.

BACKGROUND: Appropriately timed cessation of chemotherapy is an important aspect of good quality palliative care. There is wide variation in the reported rates of chemotherapy administration within the last 30 days of life. AIMS: To identify predictors of death within 30 days of receiving palliative chemotherapy, and to propose a standard definition by which oncologists and cancer centres can be compared. METHODS: Patients who received palliative chemotherapy at a regional cancer centre and its rural outreach unit between 2009 and 2011 were included. An adjusted logistic regression model, including all variables, was fit to identify predictors of death within 30 days of receiving palliative chemotherapy. RESULTS: Over a 3-year period, 1131 patients received palliative chemotherapy, 138 (12%) died within 30 days of receiving palliative chemotherapy. Predictors of death within 30 days of palliative chemotherapy were: less than 30 days contact with palliative care (odds ratio 3.30 (95% confidence interval 2.04-5.34), P < 0.001) and male gender (odds ratio 2.02 (95% confidence interval 1.24-3.31), P = 0.0049), but treating clinician, tumour chemoresponsiveness, age, body mass index and survival from initial diagnosis were not. CONCLUSION: Patients who received chemotherapy in the last 30 days of life were more likely to be male and have a shorter duration of palliative care team involvement. In this study, the observed rate of death within 30 days of chemotherapy is within the range of published data. It is recommended that a standard definition be used to benchmark medical oncology centres and individual oncologists, and to allow comparison over time.