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Paediatric cardiac surgery on cardiopulmonary bypass induces substantial physiologic changes that contribute to post-operative morbidity and mortality. Fluid overload and oedema are prevalent complications, routinely treated with diuretics. The optimal diuretic choice, timing of initiation, dose, and interval remain largely unknown.
To guide clinical practice and future studies, we used PubMed and EMBASE to systematically review the existing literature of clinical trials involving diuretics following cardiac surgery from 2000 to 2020 in children aged 0–18 years. Studies were assessed by two reviewers to ensure that they met eligibility criteria.
We identified nine studies of 430 children across four medication classes. Five studies were retrospective, and four were prospective, two of which included randomisation. All were single centre. There were five primary endpoints – urine output, acute kidney injury, fluid balance, change in serum bicarbonate level, and required dose of diuretic. Included studies showed early post-operative diuretic resistance, suggesting higher initial doses. Two studies of ethacrynic acid showed increased urine output and lower diuretic requirement compared to furosemide. Children receiving peritoneal dialysis were less likely to develop fluid overload than those receiving furosemide. Chlorothiazide, acetazolamide, and tolvaptan demonstrated potential benefit as adjuncts to traditional diuretic regimens.
Early diuretic resistance is seen in children following cardiopulmonary bypass. Ethacrynic acid appears superior to furosemide. Adjunct diuretic therapies may provide additional benefit. Study populations were heterogeneous and endpoints varied. Standardised, validated endpoints and pragmatic trial designs may allow investigators to determine the optimal diuretic, timing of initiation, dose, and interval to improve post-operative outcomes.
Targeted drug development efforts in patients with CHD are needed to standardise care, improve outcomes, and limit adverse events in the post-operative period. To identify major gaps in knowledge that can be addressed by drug development efforts and provide a rationale for current clinical practice, this review evaluates the evidence behind the most common medication classes used in the post-operative care of children with CHD undergoing cardiac surgery with cardiopulmonary bypass.
We systematically searched PubMed and EMBASE from 2000 to 2019 using a controlled vocabulary and keywords related to diuretics, vasoactives, sedatives, analgesics, pulmonary vasodilators, coagulation system medications, antiarrhythmics, steroids, and other endocrine drugs. We included studies of drugs given post-operatively to children with CHD undergoing repair or palliation with cardiopulmonary bypass.
We identified a total of 127 studies with 51,573 total children across medication classes. Most studies were retrospective cohorts at single centres. There is significant age- and disease-related variability in drug disposition, efficacy, and safety.
In this study, we discovered major gaps in knowledge for each medication class and identified areas for future research. Advances in data collection through electronic health records, novel trial methods, and collaboration can aid drug development efforts in standardising care, improving outcomes, and limiting adverse events in the post-operative period.
Infants with moderate-to-severe CHD frequently undergo cardiopulmonary bypass surgery in childhood. Morbidity and mortality are highest in those who develop post-operative low cardiac output syndrome. Vasoactive and inotropic medications are mainstays of treatment for these children, despite limited evidence supporting their use.
To help inform clinical practice, as well as the conduct of future trials, we performed a systematic review of existing literature on inotropes and vasoactives in children after cardiac surgery using the PubMed and EMBASE databases. We included studies from 2000 to 2020, and the patient population was defined as birth – 18 years of age. Two reviewers independently reviewed studies to determine final eligibility.
The final analysis included 37 papers. Collectively, selected studies reported on 12 different vasoactive and inotropic medications in 2856 children. Overall evidence supporting the use of these drugs in children after cardiopulmonary bypass was limited. The majority of studies were small with 30/37 (81%) enrolling less than 100 patients, 29/37 (78%) were not randomised, and safety and efficacy endpoints differed widely, limiting the ability to combine data for meta-analyses.
Vasoactive and inotropic support remain critical parts of post-operative care for children after cardiopulmonary bypass surgery. There is a paucity of data for the selection and dosing of vasoactives and inotropes for these patients. Despite the knowledge gaps that remain, numerous recent innovations create opportunities to rethink the conduct of clinical trials in this high-risk population.
Preoperative mechanical ventilation is associated with morbidity and mortality following CHD surgery, but prior studies lack a comprehensive analysis of how preoperative respiratory support mode and timing affects outcomes.
We retrospectively collected data on children <18 years of age undergoing cardiac surgery at an academic tertiary care medical centre. Using multivariable regression, we examined the association between modes of preoperative respiratory support (nasal cannula, high-flow nasal cannula/noninvasive ventilation, or invasive mechanical ventilation), escalation of preoperative respiratory support, and invasive mechanical ventilation on the day of surgery for three outcomes: operative mortality, postoperative length of stay, and postoperative complications. We repeated our analysis in a subcohort of neonates.
A total of 701 children underwent 800 surgical procedures, and 40% received preoperative respiratory support. Among neonates, 243 patients underwent 253 surgical procedures, and 79% received preoperative respiratory support. In multivariable analysis, all modes of preoperative respiratory support, escalation in preoperative respiratory support, and invasive mechanical ventilation on the day of surgery were associated with increased odds of prolonged length of stay in children and neonates. Children (odds ratio = 3.69, 95% CI 1.2–11.4) and neonates (odds ratio = 8.97, 95% CI 1.31–61.14) on high-flow nasal cannula/noninvasive ventilation had increased odds of operative mortality compared to those on room air.
Preoperative respiratory support is associated with prolonged length of stay and mortality following CHD surgery. Knowing how preoperative respiratory support affects outcomes may help guide surgical timing, inform prognostic conversations, and improve risk stratification models.
The ventricular assist device is being increasingly used as a “bridge-to-transplant” option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharmacotherapy. Pharmacokinetic/pharmacodynamic alterations affecting pharmacotherapy are increasingly discovered in children supported with extracorporeal membrane oxygenation, another form of mechanical circulatory support. Similarities between extracorporeal membrane oxygenation and ventricular assist devices support the hypothesis that similar alterations may exist in ventricular assist device-supported patients. We conducted a literature review to assess the current data available on pharmacokinetics/pharmacodynamics in children with ventricular assist devices. We found two adult and no paediatric pharmacokinetic/pharmacodynamic studies in ventricular assist device-supported patients. While mechanisms may be partially extrapolated from children supported with extracorporeal membrane oxygenation, dedicated investigation of the paediatric ventricular assist device population is crucial given the inherent differences between the two forms of mechanical circulatory support, and pathophysiology that is unique to these patients. Commonly used drugs such as anticoagulants and antibiotics have narrow therapeutic windows with devastating consequences if under-dosed or over-dosed. Clinical studies are urgently needed to improve outcomes and maximise the potential of ventricular assist devices in this vulnerable population.
The Permian is regarded as one of the most crucial intervals during echinoid evolution because crown group echinoids are first widely known from the Permian. New faunas provide important information regarding the diversity of echinoids during this significant interval as well as the morphological characterization of the earliest crown group and latest stem group echinoids. A new fauna from the Capitanian Lamar Member of the Bell Canyon Formation in the Guadalupe Mountains of West Texas comprises at least three new taxa, including Eotiaris guadalupensis Thompson n. sp. an indeterminate archaeocidarid, and Pronechinus? sp. All specimens represented are silicified and known from disarticulated or semiarticulated interambulacral and ambulacral plates and spines. This assemblage is one of the most diverse echinoid assemblages known from the Permian and, as such, informs the paleoecological setting in which the earliest crown group echinoids lived. This new fauna indicates that crown group echinoids occupied the same environments as stem group echinoids of the Archaeocidaridae and Proterocidaridae. Furthermore, the echinoids described herein begin to elucidate the order of character transitions that likely took place between stem group and crown group echinoids. At least one of the morphological innovations once thought to be characteristic of early crown group echinoids, crenulate tubercles, was in fact widespread in a number of stem group taxa from the Permian as well. Crenulate tubercles are reported from two taxa, and putative cidaroid style U-shaped teeth are present in the fauna. The presence of crenulate tubercles in the archaeocidarid indicates that crenulate tubercles were present in stem group echinoids, and thus the evolution of this character likely preceded the evolution of many of the synapomorphies that define the echinoid crown group.
Young children are particularly vulnerable to malnutrition as nutrition transition progresses. The present study aimed to document the prevalence, coexistence and correlates of nutritional status (stunting, overweight/obesity and anaemia) in Samoan children aged 24–59 months.
A cross-sectional community-based survey. Height and weight were used to determine prevalence of stunting (height-for-age Z-score <−2) and overweight/obesity (BMI-for-age Z-score >+2) based on WHO growth standards. Anaemia was determined using an AimStrip Hemoglobin test system (Hb <110 g/l).
Ten villages on the Samoan island of Upolu.
Mother–child pairs (n 305) recruited using convenience sampling.
Moderate or severe stunting was apparent in 20·3 % of children, 16·1 % were overweight/obese and 34·1 % were anaemic. Among the overweight/obese children, 28·6 % were also stunted and 42·9 % anaemic, indicating dual burden of malnutrition. Stunting was significantly less likely among girls (OR=0·41; 95 % CI 0·21, 0·79, P<0·01) than boys. Overweight/obesity was associated with higher family socio-economic status and decreased sugar intake (OR per 10 g/d=0·89, 95 % CI 0·80, 0·99, P=0·032). The odds of anaemia decreased with age and anaemia was more likely in children with an anaemic mother (OR=2·20; 95 % CI 1·22, 3·98, P=0·007). No child, maternal or household characteristic was associated with more than one of the nutritional status outcomes, highlighting the need for condition-specific interventions in this age group.
The observed prevalences of stunting, overweight/obesity and anaemia suggest that it is critical to invest in nutrition and develop health programmes targeting early childhood growth and development in Samoa.
To examine the use of vitamin D supplements during infancy among the participants in an international infant feeding trial.
Information about vitamin D supplementation was collected through a validated FFQ at the age of 2 weeks and monthly between the ages of 1 month and 6 months.
Infants (n 2159) with a biological family member affected by type 1 diabetes and with increased human leucocyte antigen-conferred susceptibility to type 1 diabetes from twelve European countries, the USA, Canada and Australia.
Daily use of vitamin D supplements was common during the first 6 months of life in Northern and Central Europe (>80 % of the infants), with somewhat lower rates observed in Southern Europe (>60 %). In Canada, vitamin D supplementation was more common among exclusively breast-fed than other infants (e.g. 71 % v. 44 % at 6 months of age). Less than 2 % of infants in the USA and Australia received any vitamin D supplementation. Higher gestational age, older maternal age and longer maternal education were study-wide associated with greater use of vitamin D supplements.
Most of the infants received vitamin D supplements during the first 6 months of life in the European countries, whereas in Canada only half and in the USA and Australia very few were given supplementation.
Dry bean (Phaseolus vulgaris L.) consumption is associated with reduced risk for a number of chronic diseases. In westernised societies, dry bean consumption is particularly low (approximately 2–4 kg/capita per year) and little information is available about the safety of increasing dietary intake in humans to achieve levels that prevent and control chronic diseases. In anticipation of a human intervention study to address the safety and efficacy of increasing bean consumption, a dose–response study with dietary beans was conducted to establish whether increased bean consumption in rats exhibits changes indicative of hepatic stress or toxicity. Transcript levels from a panel of stress and toxicity-related genes were analysed in female Sprague–Dawley rats fed a dose range of dietary beans that bracketed amounts relevant to human consumption globally. Cooked red bean was incorporated into a purified diet formulation at 0, 7·5, 15, 30 or 60 % w/w for the assessment of adaptive patterns of gene expression using quantitative PCR array. Of the eighty-four genes evaluated, the expressions of Cyp3a11, Cyp7a1, Fmo1, Gstm1, Mif and Ugt1a6 were elevated, whereas the expression of Hspa8 was down-regulated. Liver gene expression was not modulated in a manner indicative of an adverse response. Only the expression of the cholesterol 7α hydoxylase and UDP-glucuronosyltransferase genes increased in a dose-dependent manner at nutritionally relevant dietary bean concentrations. These candidate genes may contribute to the health benefits attributed to increased bean consumption.
To evaluate the impact of a multifaceted intervention on compliance with evidence-based therapies and ventilator-associated pneumonia (VAP) rates.
Collaborative cohort before-after study.
Intensive care units (ICUs) predominantly in Michigan.
We implemented a multifaceted intervention to improve compliance with 5 evidence-based recommendations for mechanically ventilated patients and to prevent VAP. A standardized CDC definition of VAP was used and maintained at each site, and data on the number of VAPs and ventilator-days were obtained from the hospital's infection preventionists. Baseline data were reported and postimplementation data were reported for 30 months. VAP rates (in cases per 1,000 ventilator-days) were calculated as the proportion of ventilator-days per quarter in which patients received all 5 therapies in the ventilator care bundle. Two interventions to improve safety culture and communication were implemented first.
One hundred twelve ICUs reporting 3,228 ICU-months and 550,800 ventilator-days were included. The overall median VAP rate decreased from 5.5 cases (mean, 6.9 cases) per 1,000 ventilator-days at baseline to 0 cases (mean, 3.4 cases) at 16–18 months after implementation (P < .001) and 0 cases (mean, 2.4 cases) at 28-30 months after implementation (P < .001). Compared to baseline, VAP rates decreased during all observation periods, with incidence rate ratios of 0.51 (95% confidence interval, 0.41–0.64) at 16–18 months after implementation and 0.29 (95% confidence interval, 0.24–0.34) at 28–30 months after implementation. Compliance with evidence-based therapies increased from 32% at baseline to 75% at 16–18 months after implementation (P < .001) and 84% at 28–30 months after implementation (P < .001).
A multifaceted intervention was associated with an increased use of evidence-based therapies and a substantial (up to 71%) and sustained (up to 2.5 years) decrease in VAP rates.
Maternal nutritional status before and during pregnancy is important for the growth and development of the fetus. The effects of pre-pregnancy nutrition (estimated by maternal size) are well documented. There is little information in today's Western society on the effect of maternal nutrition during pregnancy on the fetus. The aim of the study was to describe dietary patterns of a cohort of mothers during pregnancy (using principal components analysis with a varimax rotation) and assess the effect of these dietary patterns on the risk of delivering a small-for-gestational-age (SGA) baby. The study was a case–control study investigating factors related to SGA. The population was 1714 subjects in Auckland, New Zealand, born between October 1995 and November 1997, about half of whom were born SGA ( ≤ 10th percentile for sex and gestation). Maternal dietary information was collected using FFQ after delivery for the first and last months of pregnancy. Three dietary patterns (traditional, junk and fusion) were defined. Factors associated with these dietary patterns when examined in multivariable analyses included marital status, maternal weight, maternal age and ethnicity. In multivariable analysis, mothers who had higher ‘traditional’ diet scores in early pregnancy were less likely to deliver a SGA infant (OR = 0·86; 95 % CI 0·75, 0·99). Maternal diet, particularly in early pregnancy, is important for the development of the fetus. Socio-demographic factors tend to be significantly related to dietary patterns, suggesting that extra resources may be necessary for disadvantaged mothers to ensure good nutrition in pregnancy.
The Working Group FITS (WG-FITS) is the international control authority for the Flexible Image Transport System (FITS) data format. The WG-FITS was formed in 1988 by a formal resolution of the IAU XX General Assembly in Baltimore (MD, USA), 1988, to maintain the existing FITS standards and to approve future extensions to FITS.
The potential environmental and health concerns surrounding actinides and the use of nuclear fuels limits the acceptance of nuclear power by the public. This in turn, hinders the capability of this country to take advantage of nuclear power. Expanding our fundamental knowledge of actinide coordination chemistry will allow for the development of improved actinide sensors, new separations methods, or new means of radioactive waste remediation. We have designed and optimized a solution-phase parallel method for the synthesis of a library of symmetrical 2-quinoxalinol salens, Schiff-base type ligands with a 2-quinoxalinol incorporated into the salen backbone. This combines the rigid salen coordination framework with the quinoxaline properties that impart properties for use in colorimetric or fluorescent sensors. These have now been incorporated into organic soluble resins for metal extraction.
The business meeting began with a brief review of the current rules and procedures of the WG, which are documented on the WG web page. Four regional FITS committees have been established by the WG, covering North American, Europe, Japan, and Australian/New Zealand, to provide advice to the WG on pending proposals. While it is recognized that this committee structure might need to be revised to provide representation to other regions, the current system is working well, and there were no motions to make any changes at this time.