Electrical Cardiometry during transition and short-term outcome in very preterm infants: a prospective observational study.

The purpose of this study is to evaluate the association of Electrical Cardiometry (EC)-derived cardiac output indexed to weight (CO) and its changes during the first 48 h in relation to adverse short-term outcome in very preterm infants. In this prospective observational study of preterm infants < 32 weeks gestational age (GA), the combined adverse outcome was defined as mortality or abnormal cranial ultrasound (any grade intracranial hemorrhage (ICH) or periventricular leukomalacia) within the first 2 weeks postnatally. Logistic regression models were used to investigate the association between median CO and outcome and mixed-effects models for the time trajectory of CO. In the absence of device-specific thresholds for low or high CO, no thresholds were used in our analysis. Fifty-three infants (median (IQR) GA 29.0 (25.4-30.6) weeks, birthweight 1020 (745-1505) g) were included in the analysis. Median CO was 241 (197-275) mL/kg/min for the adverse outcome and 198 (175-227) mL/kg/min for normal outcome (odds ratio (OR) (95% confidence interval (95% CI)), 1.01 (1.00 to 1.03); p = 0.028). After adjustment for GA, the difference was not significant (adjusted OR (95% CI), 1.01 (0.99 to 1.02); p = 0.373). CO trajectory did not differ by outcome (p = 0.352). A post hoc analysis revealed an association between CO time trajectory and ICH ≥ grade 2.          Conclusions: EC-derived CO estimates within 48 h postnatally were not independently associated with brain injury (any grade) or mortality in the first 14 days of life. CO time trajectory was found to be associated with ICH ≥ grade 2. What is Known: • Bioreactance-derived cardiac output indexed to bodyweight (CO) in the transitional period has been associated with adverse short-term outcome in preterm infants. What is New: • Electrical Cardiometry (EC)-derived CO measurements in very preterm infants during the transitional period are not independently associated with adverse outcome (death or ultrasound detected brain damage) within 2 weeks postnatally. • In the first 48 h EC-derived CO increases over time and is higher in extremely preterm infants compared to very preterm and differs from previously reported bioreactance-derived CO values.

Formation of multicellular colonies by choanoflagellates increases susceptibility to capture by amoeboid predators.

Many heterotrophic microbial eukaryotes are size-selective feeders. Some microorganisms increase their size by forming multicellular colonies. We used choanoflagellates, Salpingoeca helianthica, which can be unicellular or form multicellular colonies, to study the effects of multicellularity on vulnerability to predation by the raptorial protozoan predator, Amoeba proteus, which captures prey with pseudopodia. Videomicrography used to measure the behavior of interacting S. helianthica and A. proteus revealed that large choanoflagellate colonies were more susceptible to capture than were small colonies or single cells. Swimming colonies produced larger flow fields than did swimming unicellular choanoflagellates, and the distance of S. helianthica from A. proteus when pseudopod formation started was greater for colonies than for single cells. Prey size did not affect the number of pseudopodia formed and the time between their formation, pulsatile kinematics and speed of extension by pseudopodia, or percent of prey lost by the predator. S. helianthica did not change swimming speed or execute escape maneuvers in response to being pursued by pseudopodia, so size-selective feeding by A. proteus was due to predator behavior rather than prey escape. Our results do not support the theory that the selective advantage of becoming multicellular by choanoflagellate-like ancestors of animals was reduced susceptibility to protozoan predation.

Nonstationary coupling between heart rate and perfusion index in extremely preterm infants in the first day of life.

Objective.Adaptation to the extra-uterine environment presents many challenges for infants born less than 28 weeks of gestation. Quantitative analysis of readily available physiological signals at the cotside could provide valuable information during this critical time. We aim to assess the time-varying coupling between heart rate (HR) and perfusion index (PI) over the first 24 h after birth and relate this coupling to gestational age (GA), inotropic therapy, and short-term clinical outcome.Approach.We develop new nonstationary measures of coupling to summarise both frequency- and direction-dependent coupling. These measures employ a coherence measure capable of measuring time-varying Granger casuality using a short-time information partial-directed coherence function. Measures are correlated with GA, inotropic therapy (yes/no), and outcome (adverse/normal).Main results.In a cohort of 99 extremely preterm infants (<28 weeks of gestation), we find weak but significant coupling in both the HR → PI and PI → HR directions (P< 0.05). HR → PI coupling increases with maturation (correlationr = 0.26;P = 0.011). PI → HR coupling increases with inotrope administration (r = 0.27;P = 0.007). And nonstationary features of PI → HR coupling are associated with adverse outcome (r = 0.27;P = 0.009).Significance.Nonstationary features are necessary to distinguish different coupling types for complex biomedical systems. Time-varying directional coupling between PI and HR provides objective and independent biomarkers of adverse outcome in extremely preterm infants.

Assertive outreach treatment versus care as usual for the treatment of high-need, high-cost alcohol related frequent attenders: study protocol for a randomised controlled trial.

BACKGROUND: Alcohol-related hospital admissions have doubled in the last ten years to > 1.2 m per year in England. High-need, high-cost (HNHC) alcohol-related frequent attenders (ARFA) are a relatively small subgroup of patients, having multiple admissions or attendances from alcohol during a short time period. This trial aims to test the effectiveness of an assertive outreach treatment (AOT) approach in improving clinical outcomes for ARFA, and reducing resource use in the acute setting. METHODS: One hundred and sixty ARFA patients will be recruited and following baseline assessment, randomly assigned to AOT plus care as usual (CAU) or CAU alone in equal numbers. Baseline assessment includes alcohol consumption and related problems, physical and mental health comorbidity and health and social care service use in the previous 6 months using standard validated tools, plus a measure of resource use. Follow-up assessments at 6 and 12 months after randomization includes the same tools as baseline plus standard measure of patient satisfaction. Outcomes for CAU + AOT and CAU at 6 and 12 months will be compared, controlling for pre-specified baseline measures. Primary outcome will be percentage of days abstinent at 12 months. Secondary outcomes include emergency department (ED) attendance, number and length of hospital admissions, alcohol consumption, alcohol-related problems, other health service use, mental and physical comorbidity 6 and 12 months post intervention. Health economic analysis will estimate the economic impact of AOT from health, social care and societal perspectives and explore cost-effectiveness in terms of quality adjusted life years and alcohol consumption at 12-month follow-up. DISCUSSION: AOT models piloted with alcohol dependent patients have demonstrated significant reductions in alcohol consumption and use of unplanned National Health Service (NHS) care, with increased engagement with alcohol treatment services, compared with patients receiving CAU. While AOT interventions are costlier per case than current standard care in the UK, the rationale for targeting HNHC ARFAs is because of their disproportionate contribution to overall alcohol burden on the NHS. No previous studies have evaluated the clinical and cost-effectiveness of AOT for HNHC ARFAs: this randomized controlled trial (RCT) targeting ARFAs across five South London NHS Trusts is the first. TRIAL REGISTRATION: International standard randomized controlled trial number (ISRCTN) registry: ISRCTN67000214, retrospectively registered 26/11/2016.

Monitoring cerebral oxygenation of preterm infants using a neonatal specific sensor.

INTRODUCTION: Cerebral oxygenation (rcSO2) monitoring in preterm infants may identify periods of cerebral hypoxia or hyperoxia. We hypothesised that there was a relationship between rcSO2 values and short term outcome in infants of GA < 32weeks. METHODS: RcSO2 values were recorded for the first 48 h of life using an INVOS monitor with a neonatal sensor. The association between cranial ultrasound scan measured brain injury and rcSO2 was assessed. RESULTS: 120 infants were included. Sixty-nine percent (83) of infants had a normal outcome (no IVH, no PVL, and survival at 1 month); less than one-quarter, 22% (26), had low grade IVH 1 or 2 (moderate outcome); and 9% (11) of infants had a severe outcome (IVH ≥ 3, PVL or died before 1 month age). rcSO2 values were lower for infants GA < 28weeks when compared with those GA 28-32, p < 0.001. There was no difference in absolute rcSO2 values between the three outcome groups but a greater degree of cerebral hypoxia was associated with preterm infants who had low grade 1 or 2 IVH. CONCLUSION: Infants of GA < 28 weeks have lower cerebral oxygenation in the first 2 days of life. A greater degree of hypoxia was seen in infants with grade 1 or 2 haemorrhage. Normative ranges need to be gestation specific.

Functional maturation in preterm infants measured by serial recording of cortical activity.

Minimally invasive, automated cot-side tools for monitoring early neurological development can be used to guide individual treatment and benchmark novel interventional studies. We develop an automated estimate of the EEG maturational age (EMA) for application to serial recordings in preterm infants. The EMA estimate was based on a combination of 23 computational features estimated from both the full EEG recording and a period of low EEG activity (46 features in total). The combination function (support vector regression) was trained using 101 serial EEG recordings from 39 preterm infants with a gestational age less than 28 weeks and normal neurodevelopmental outcome at 12 months of age. EEG recordings were performed from 24 to 38 weeks post-menstrual age (PMA). The correlation between the EMA and the clinically determined PMA at the time of EEG recording was 0.936 (95%CI: 0.932-0.976; n = 39). All infants had an increase in EMA between the first and last EEG recording and 57/62 (92%) of repeated measures within an infant had an increasing EMA with PMA of EEG recording. The EMA is a surrogate measure of age that can accurately determine brain maturation in preterm infants.

Estimating functional brain maturity in very and extremely preterm neonates using automated analysis of the electroencephalogram.

OBJECTIVE: To develop an automated estimate of EEG maturational age (EMA) for preterm neonates. METHODS: The EMA estimator was based on the analysis of hourly epochs of EEG from 49 neonates with gestational age (GA) ranging from 23 to 32weeks. Neonates had appropriate EEG for GA based on visual interpretation of the EEG. The EMA estimator used a linear combination (support vector regression) of a subset of 41 features based on amplitude, temporal and spatial characteristics of EEG segments. Estimator performance was measured with the mean square error (MSE), standard deviation of the estimate (SD) and the percentage error (SE) between the known GA and estimated EMA. RESULTS: The EMA estimator provided an unbiased estimate of EMA with a MSE of 82days (SD=9.1days; SE=4.8%) which was significantly lower than a nominal reading (the mean GA in the dataset; MSE of 267days, SD of 16.3days, SE=8.4%: p<0.001). The EMA estimator with the lowest MSE used amplitude, spatial and temporal EEG characteristics. CONCLUSIONS: The proposed automated EMA estimator provides an accurate estimate of EMA in early preterm neonates. SIGNIFICANCE: Automated analysis of the EEG provides a widely accessible, noninvasive and continuous assessment of functional brain maturity.

Perfusion index in the preterm infant immediately after birth.

AIM: To evaluate PI in preterm infants during the first 10 min of life. DESIGN/METHODS: An observational study was conducted in the delivery room on preterm infants (less than 32 week gestation). PI values were obtained from a pre ductal saturation probe placed on the right wrist. Analysis was performed on the first 10 min of data to investigate the correlation of PI with gestational age, heart rate, blood pressure, and lactate values. RESULTS: 33 infants with a median gestational age of 29 wks (IQR, 26-30 wks) and median birth weight of 1205 g (IQR, 925-1520 g) were included for analysis. The overall median PI value for the first 10 min was 1.3 (IQR, 0.86-1.68). There was no significant correlation found between delivery room PI and gestational age(r=0.28, 95% CI: -0.09, 0.59), lactate levels (r=-0.25, 95% CI: -0.62, 0.18) and blood pressure values (r=-0.18, 95% CI: -0.46, 0.20). An average correlation value of r=-0.417 (95% CI: - 0.531, -0.253) was found between PI and heart rate values. There was no statistical difference between the median of the median PI value over the first 5 min of life compared to the second 5 min (p=0.22). Variability, as quantified by the IQR, was higher in the first 5 min compared to the second 5 min: median of 0.5(IQR, 0.27, 0.92) vs 0.2(IQR, 0.10, 0.30) (p<0.00). CONCLUSIONS: Delivery room PI values are easily obtained, however, have significant variability over the first 5 min of life and may add little to delivery room assessment.

The microbiological and sustainability effects of washing anaesthesia breathing circuits less frequently.

In the presence of single-use airway filters, we quantified anaesthetic circuit aerobic microbial contamination rates when changed every 24 h, 48 h and 7 days. Microbiological samples were taken from the interior of 305 anaesthetic breathing circuits over a 15-month period (3197 operations). There was no significant difference in the proportion of contaminated circuits when changed every 24 h (57/105 (54%, 95% CI 45-64%)) compared with 48 h (43/100 (43%, 95% CI 33-53%, p = 0.12)) and up to 7 days (46/100 (46%, 95% CI 36-56%, p = 0.26)). Median bacterial counts were not increased at 48 h or 7 days provided circuits were routinely emptied of condensate. Annual savings for one hospital (six operating theatres) were $AU 5219 (£3079, €3654, $US 4846) and a 57% decrease in anaesthesia circuit steriliser loads associated with a yearly saving of 2760 kWh of electricity and 48 000 l of water. Our findings suggest that extended circuit use from 24 h up to 7 days does not significantly increase bacterial contamination, and is associated with labour, energy, water and financial savings.

Artefact detection in neonatal EEG.

Artefact detection is an important component of any automated EEG analysis. It is of particular importance in analyses such as sleep state detection and EEG grading where there is no null state. We propose a general artefact detection system (GADS) based on the analysis of the neonatal EEG. This system aims to detect both major and minor artefacts (a distinction based primarily on amplitude). As a result, a two-stage system was constructed based on 14 features extracted from EEG epochs at multiple time scales: [2, 4, 16, 32]s. These features were combined in a support vector machine (SVM) in order to determine the presence of absence of artefact. The performance of the GADS was estimated using a leave-one-out cross-validation applied to a database of hour long recordings from 51 neonates. The median AUC was 1.00 (IQR: 0.95-1.00) for the detection of major artefacts and 0.89 (IQR: 0.83-0.95) for the detection of minor artefacts.

A novel, validated method to quantify breast cancer-related lymphedema (BCRL) following bilateral breast surgery.

We sought to develop a formula to quantify breast cancer-related lymphedema (BCRL) after bilateral breast surgery, which functions independently of the contralateral arm and accounts for fluctuations in patient weight. Perometer arm measurements from 265 unilateral breast surgery patients were analyzed. We assessed the relationship between change in patient weight and contralateral arm volume and developed a weight-adjusted volume change formula (WAC). The WAC formula and previously-established RVC formula were compared for classification of BCRL (> or = 10% volume increase) in unilateral breast surgery patients. We then evaluated BCRL incidence using the WAC formula in 225 bilateral mastectomy patients. Change in patient weight and contralateral arm volume demonstrated an approximately linear relationship. Weight-adjusted arm volume change (WAC) was therefore calculated as WAC = (A2*W1)/(W2*A1) - 1 where A1 is pre-operative and A2 is post-operative arm volume, and W1, W2 are the patient's corresponding weights. In the unilateral analysis, there was no significant difference in number of patients classified as having BCRL using the RVC and WAC formulas (p = 0.65). In bilateral mastectomy patients 11.1% (25/225) developed BCRL, defined as > or = 10% WAC. Independent risk factors for lymphedema included axillary lymph node dissection (ALND) and higher pre-operative BMI (p<0.05). Use of this weight-adjusted arm volume change formula should be of value for quantification of BCRL after bilateral breast surgery.

A nonparametric feature for neonatal EEG seizure detection based on a representation of pseudo-periodicity.

Automated methods of neonatal EEG seizure detection attempt to highlight the evolving, stereotypical, pseudo-periodic, nature of EEG seizure while rejecting the nonstationary, modulated, coloured stochastic background in the presence of various EEG artefacts. An important aspect of neonatal seizure detection is, therefore, the accurate representation and detection of pseudo-periodicity in the neonatal EEG. This paper describes a method of detecting pseudo-periodic components associated with neonatal EEG seizure based on a novel signal representation; the nonstationary frequency marginal (NFM). The NFM can be considered as an alternative time-frequency distribution (TFD) frequency marginal. This method integrates the TFD along data-dependent, time-frequency paths that are automatically extracted from the TFD using an edge linking procedure and has the advantage of reducing the dimension of a TFD. The reduction in dimension simplifies the process of estimating a decision statistic designed for the detection of the pseudo-periodicity associated with neonatal EEG seizure. The use of the NFM resulted in a significant detection improvement compared to existing stationary and nonstationary methods. The decision statistic estimated using the NFM was then combined with a measurement of EEG amplitude and nominal pre- and post-processing stages to form a seizure detection algorithm. This algorithm was tested on a neonatal EEG database of 18 neonates, 826 h in length with 1389 seizures, and achieved comparable performance to existing second generation algorithms (a median receiver operating characteristic area of 0.902; IQR 0.835-0.943 across 18 neonates).

Kalman filter-based time-varying cortical connectivity analysis of newborn EEG.

Multivariate Granger causality in the time-frequency domain as a representation of time-varying cortical connectivity in the brain has been investigated for the adult case. This is, however, not the case in newborns as the nature of the transient changes in the newborn EEG is different from that of adults. This paper aims to evaluate the performance of the time-varying versions of the two popular Granger causality measures, namely Partial Directed Coherence (PDC) and direct Directed Transfer Function (dDTF). The parameters of the time-varying AR, that models the inter-channel interactions, are estimated using Dual Extended Kalman Filter (DEKF) as it accounts for both non-stationarity and non-linearity behaviors of the EEG. Using simulated data, we show that fast changing cortical connectivity between channels can be measured more accurately using the time-varying PDC. The performance of the time-varying PDC is also tested on a neonatal EEG exhibiting seizure.

Classification of eating disturbance in children and adolescents: proposed changes for the DSM-V.

Childhood and adolescence are critical periods of neural development and physical growth. The malnutrition and related medical complications resulting from eating disorders such as anorexia nervosa (AN), bulimia nervosa (BN) and eating disorder not otherwise specified may have more severe and potentially more protracted consequences during youth than during other age periods. The consensus opinion of an international workgroup of experts on the diagnosis and treatment of child and adolescent eating disorders is that (a) lower and more developmentally sensitive thresholds of symptom severity (e.g. lower frequency of purging behaviours, significant deviations from growth curves as indicators of clinical severity) be used as diagnostic boundaries for children and adolescents, (b) behavioural indicators of psychological features of eating disorders be considered even in the absence of direct self-report of such symptoms and (c) multiple informants (e.g. parents) be used to ascertain symptom profiles. Collectively, these recommendations will permit earlier identification and intervention to prevent the exacerbation of eating disorder symptoms.

Extent of prevalence and size of flat neoplasms in a heterogeneous population undergoing routine colorectal cancer screening.

BACKGROUND: The importance of identifying flat colorectal neoplasms is increasingly appreciated, although the extent of prevalence of these lesions in a general population is not known. OBJECTIVE: To determine the extent of prevalence of flat neoplasms in a diverse population undergoing routine endoscopic screening for colorectal cancer. DESIGN: Patients referred to the Colorectal Cancer Screening Clinic over a 12-month period (n = 642). RESULTS: The patient population was 56% African American and 21% Caucasian; with a mean age of 59 + or - 9 years. Flat neoplasms were detected in 5.5% of all patients, similar to that reported elsewhere, with extent of prevalence being similar regardless of gender or race. Average size of flat neoplasms was of 2.8 + or - 2.3 mm (range 1-20 mm). However, there was no evidence of advanced pathology in any of the flat neoplasms identified. CONCLUSIONS: Flat neoplasms are common but may not be associated with advanced pathology in a population undergoing routine screening.

Risk in the mist? Deriving data to quantify microbial health risks associated with aerosol generation by water-efficient devices during typical domestic water-using activities.

The aim of this study was to address existing data gaps and to determine the size distribution of aerosols associated with water-efficient devices during typical domestic activities. This information is important to assist in understanding infection spread during water-using activities and in designing water regulations. Three water-using scenarios were evaluated: i) showering using a water-efficient showerhead; ii) use of a high pressure spray unit for cleaning cars and iii) toilet flushing using a dual flush low volume flush device. For each scenario a control condition (conventional lower efficiency device) was selected for benchmarking purposes. Shower module results highlighted the complexity of particle generation and removal processes and showed that more than 90% of total particle mass in the breathing zone was attributed to particle diameters greater than 6 mum. Conversely, results for car washing experiments showed that particle diameters up to 6 mum constituted the major part of the total mass generated by both water-efficient and conventional devices. Even under worse case scenario conditions for toilet flushing, particle measurements were at or below the level of detection of the measuring instrumentation. The data provide information that assists in health risk assessment and in determining future research directions, including methodological aspects.

Influence of sample preservation on endotoxin measurement in water.

Appropriate preservation of a range of water types prior to analysis for endotoxin was investigated, including sample storage and addition of sodium thiosulphate. Biologically active endotoxin in water samples was assayed using a chromogenic Limulus Amoebocyte Lysate (LAL) assay. Statistical analysis of measured mean endotoxin levels obtained for samples with and without sodium thiosulphate showed no significant difference in results. There was a 44% mean decline in the concentration of detectable endotoxin in water samples stored at -80 degrees C for 4 weeks compared with samples stored at 4 degrees C and analysed within 24 hours. Freezing of water samples at -80 degrees C in pyrogen-free containers for 4 weeks or longer, then thawing may lead to considerable endotoxin loss; however the addition of sodium thiosulphate to water samples interferes minimally with the LAL assay. These results provide methodological information that can be used to assist researchers in future water endotoxin monitoring studies. The validation and standardisation of water sample preservation protocols are necessary, given the likely increase in the quantification of endotoxin levels in a variety of water sources and the use of such results for health effect determinations.

European Antibiotic Awareness Day, 2008 - the first Europe-wide public information campaign on prudent antibiotic use: methods and survey of activities in participating countries.

Antibiotic resistance is a major European and global public health problem and is, for a large part, driven by misuse of antibiotics. Hence, reducing unnecessary antibiotic use, particularly for the treatment of certain respiratory tract infections where they are not needed, is a public health priority. The success of national awareness campaigns to educate the public and primary care prescribers about appropriate antibiotic use in Belgium and France stimulated a European initiative coordinated by the European Centre for Disease Prevention and Control (ECDC), and named European Antibiotic Awareness Day (EAAD), to take place each year on 18 November. Specific campaign materials, including key messages, logos, slogans and a media toolkit, were developed and made available for use in European countries. The focus of the first EAAD campaign was about not taking antibiotics for viral infections such as colds and flu. A post-campaign survey was conducted in January 2009. Thirty-two European countries participated in the first EAAD, producing information materials and implementing activities to mark EAAD. Media coverage peaked on 18 and 19 November. At EU level, EAAD was launched at a scientific meeting in the European Parliament, Strasbourg. The event received EU political engagement through support from the EU Commissioner for Health, the Slovenian and French EU Presidencies, and Members of the European Parliament. Critical factors that led to the success of the first EAAD were good cooperation and process for building the campaign, strong political and stakeholder support and development of campaign materials based on scientific evidence. Countries indicated wide support for another EAAD in 2009. For this purpose, ECDC is developing several TV spots as well as a second set of EAAD campaign materials targeting primary care prescribers.

Improving blood-borne viral diagnosis; clinical audit of the uptake of dried blood spot testing offered by a substance misuse service.

SUMMARY: The diagnosis of blood-borne viral infection amongst drug injectors in Wales is limited by a poor uptake of diagnostic testing; recent research suggests that dried blood spot (DBS) sample collection, rather than venepuncture, may improve diagnostic rates. We carried out an audit of the uptake of DBS testing for hepatitis C, hepatitis B and HIV amongst drug injectors attending a substance misuse service (SMS) in the first year of DBS testing being routinely offered to clients (1 May 2007 to 30 April 2008) and compared the uptake to venepuncture testing of SMS clients in the previous year. Uptake of DBS testing for hepatitis C, hepatitis B and HIV was almost six times greater than the uptake of venepuncture testing amongst clients of the SMS in the previous year. The data are consistent with the hypothesis that DBS testing can increase the uptake of blood-borne viral testing amongst current and ex-drug injectors. We accept that part of the almost sixfold increase in diagnostic testing observed in the first year of DBS testing may be due to an increase in awareness amongst drug injectors of testing opportunities and a prioritization of testing by the SMS. Nonetheless the dramatic increase in uptake demonstrates that DBS testing is acceptable to drug injectors and should be subject to more rigorous trials to evaluate its potential impact on diagnosis.