Effect of constant-DI pacing on single cell pacing dynamics.

Cardiac alternans, beat-to-beat alternations in action potential duration, is a precursor to fatal arrhythmias such as ventricular fibrillation. Previous research has shown that voltage driven alternans can be suppressed by application of a constant diastolic interval (DI) pacing protocol. However, the effect of constant-DI pacing on cardiac cell dynamics and its interaction with the intracellular calcium cycle remains to be determined. Therefore, we aimed to examine the effects of constant-DI pacing on the dynamical behavior of a single-cell numerical model of cardiac action potential and the influence of voltage-calcium (V-Ca) coupling on it. Single cell dynamics were analyzed in the vicinity of the bifurcation point using a hybrid pacing protocol, a combination of constant-basic cycle length (BCL) and constant-DI pacing. We demonstrated that in a small region beneath the bifurcation point, constant-DI pacing caused the cardiac cell to remain alternans-free after switching to the constant-BCL pacing, thus introducing a region of bistability (RB). The size of the RB increased with stronger V-Ca coupling and was diminished with weaker V-Ca coupling. Overall, our findings demonstrate that the application of constant-DI pacing on cardiac cells with strong V-Ca coupling may induce permanent changes to cardiac cell dynamics increasing the utility of constant-DI pacing.

Response of bispectral index to neuromuscular block in awake volunteers.

BACKGROUND: The bispectral index (BIS) monitor is a quantitative electroencephalographic (EEG) device that is widely used to assess the hypnotic component of anaesthesia, especially when neuromuscular blocking drugs are used. It has been shown that the BIS is sensitive to changes in electromyogram (EMG) activity in anaesthetized patients. A single study using an earlier version of the BIS showed that decreased EMG activity caused the BIS to decrease even in awake subjects, to levels that suggested deep sedation and anaesthesia. METHODS: We administered suxamethonium and rocuronium to 10 volunteers who were fully awake, to determine whether the BIS decreased in response to neuromuscular block alone. An isolated forearm technique was used for communication during the experiment. Two versions of the BIS monitor were used, both of which are in current use. Sugammadex was used to antagonise the neuromuscular block attributable to rocuronium. RESULTS: The BIS decreased after the onset of neuromuscular block in both monitors, to values as low as 44 and 47, and did not return to pre-test levels until after the return of movement. The BIS showed a two-stage decrease, with an immediate reduction to values around 80, and then several minutes later, a sharp decrease to lower values. In some subjects, there were periods where the BIS was <60 for several minutes. The response was similar for both suxamethonium and rocuronium. Neither monitor was consistently superior in reporting the true state of awareness. CONCLUSIONS: These results suggest that the BIS monitor requires muscle activity, in addition to an awake EEG, in order to generate values indicating that the subject is awake. Consequently, BIS may be an unreliable indicator of awareness in patients who have received neuromuscular blocking drugs. CLINICAL TRIAL REGISTRY NUMBER: ACTRN12613000587707.

Fetal hemivertebra: associations and perinatal outcome.

OBJECTIVES: To assess the accuracy of antenatal diagnosis of hemivertebra, to quantify the association with coexisting anomalies and to determine the perinatal outcome. METHOD: This was a retrospective observational study of all cases of suspected fetal or neonatal hemivertebra identified via the UK Southwest Congenital Anomaly Register (SWCAR) between 2002 and 2012. RESULTS: From a total of 88 cases of hemivertebra identified during the study period, data were obtained for 67 of them: 45 (10 isolated and 35 with coexisting anomalies) cases were suspected antenatally and 22 (10 isolated and 12 with coexisting anomalies) were diagnosed postnatally. Of the cases detected postnatally, five (four with coexisting anomalies) were unsuspected and diagnosed at postmortem examination. The most commonly associated anomalies included additional skeletal abnormalities (n = 16), genitourinary abnormalities (n = 10), VATER/VACTERL association (n = 5), cardiac abnormalities (n = 4) and central nervous system abnormalities (n = 4). In cases with coexisting anomalies there was a 48% fetal/neonatal loss, compared to 19% in cases with isolated hemivertebra. CONCLUSIONS: Although antenatal diagnosis of hemivertebra was accurate, a third of the cases were diagnosed only postnatally. These data suggest a difficulty in antenatal diagnosis of the condition. The majority of cases of hemivertebra had coexisting anomalies, and in these cases the rate of perinatal loss was high. These data should be useful in providing additional information for counseling when a diagnosis of hemivertebra is made.

Improving postgraduate clinical assessment tools: the introduction of video recordings to assess decision making.

BACKGROUND: Competency in the management of acutely unwell patients has not previously been formally assessed as part of an objective structured clinical examination (OSCE). AIM: The reliability of the paediatric postgraduate OSCE was calculated. An objective structured video examination was designed to assess candidates' clinical decision making ability when managing acutely unwell children. METHODS: The performance of 3522 postgraduate paediatric trainees was assessed (2006-2008). OSCE reliability was determined using Cronbach's alpha and mean inter-item correlation. Performance in the video station was compared with overall performance (not including video station; Mann-Whitney U) and video station scores correlated with individual station scores (Spearman's Rho correlation coefficient). RESULTS: Clinical examination pass rates for the 684 UK graduates, 1608 overseas candidates training in the UK and 1104 overseas candidates training overseas were 69.7%, 28% and 22.3%, respectively (graduation information not available for 126 candidates). Cronbach's alpha was 0.62. Mean inter-item correlation was 0.15. Candidates who passed the OSCE overall had significantly higher scores on the video station (t(3520) = 14.48); p < 0.001). There was significant positive correlation between scores on the video station, individual stations and overall total score (r's = 0.300; p = 0.001). CONCLUSIONS: The postgraduate paediatric OSCE provides a sound and valid means of assessing clinical skills at the postgraduate level. The video station provides an important new method of assessment. Its use in other postgraduate clinical examinations should be explored.

Postnatal intravenous steroids and long-term neurological outcome: recommendations from meta-analyses.

Postnatal steroids have been widely used to facilitate the extubation of ventilator-dependent preterm infants. Reports published in the late 1990s and early 2000s raised concerns about their long-term impact on neurodevelopmental outcomes. Since then, postnatal steroid use has declined sharply, but they continue to be regarded by many clinicians as an essential part of neonatal care, and there is considerable confusion as to the most appropriate time to use them. This review examines the meta-analyses of the relationship between intravenous postnatal steroids and neurodevelopmental impairment, and provides recommendations for their use based upon that body of evidence.

Minidex: very low dose dexamethasone (0.05 mg/kg/day) in chronic lung disease.

OBJECTIVE: Postnatal dexamethasone therapy is controversial. This study aimed to determine the short-term effects of Minidex (low-dose dexamethasone 0.05 mg/kg/day) on ventilator-dependent preterm babies. METHODS: Very preterm babies (less than 30 weeks of gestation or under 1500 g) who were ventilator dependent at over 2 weeks of life and received Minidex therapy (low-dose dexamethasone 0.05 mg/kg/day for 10 days followed by alternate-day doses for 6 days) were compared retrospectively to a matched comparison group who received neither Minidex nor standard-dose dexamethasone. RESULTS: 50 babies who received Minidex were compared to a comparison group of 26 babies. Babies treated with Minidex extubated significantly faster than controls, Cox regression hazard ratio 6.24 (95% CI 2.34 to 16.63). By day 4, 34% of babies treated with Minidex had extubated but no controls had. Babies who received Minidex showed significant improvements in both ventilatory index and oxygen requirements, had no increased rate of clinical hypertension (OR 1.16 (95% CI 0.42 to 3.21)) or hyperglycaemia (OR 1.55 (95% CI 0.44 to 5.45)) and had a similar rate of chronic lung disease at 36 weeks' corrected age (OR 1.61 (95% CI 0.62 to 4.22)). No baby developed gastrointestinal perforation or haemorrhage. CONCLUSION: Minidex therapy facilitates extubation and is not associated with clinically significant short-term side effects. A randomised controlled trial is required to further assess efficacy and long-term outcomes.

Perforation of and intubation through the palatoglossal fold.

Perforation of pharyngeal soft tissues on intubation is rare. We present a case where the endotracheal tube punctured the palatoglossal fold before passing into the trachea. The patient was ventilated for eight days in intensive care before identification of the complication. It is difficult to estimate the frequency of pharyngeal perforation as it rarely occurs. There is however; an increased incidence in difficult intubations, emergency airway management, inexperienced operators and technique used.

Gastrooesophageal reflux disease in preterm infants: current management and diagnostic dilemmas.

Gastrooesophageal reflux disease (GORD) provides a diagnostic and therapeutic challenge to many neonatologists. Reflux of gastric contents is common in preterm infants but usually not pathological. GORD is frequently diagnosed despite the lack of a fully identified clinical syndrome and of a truly valid diagnostic test. Treatment modalities, for which there is little convincing evidence regarding efficacy, are commonly instigated for troublesome symptoms attributed to GORD. Diagnosis is so problematic in preterm infants that GORD is starting to be described as the clinical syndrome that responds to anti-reflux treatment. We discuss the dilemmas facing us when dealing with this condition, summarise the best available evidence regarding diagnosis and management, and use it to inform a suggested treatment pathway. We introduce the concept of a clinical scoring system to aid the diagnosis and monitoring of GORD in preterm infants and highlight areas where further research would be beneficial.

Point-of-care testing of neonatal coagulation.

The aim of this validation study was to compare prothrombin time (PT) and activated partial thromboplastin time (APTT) results from a point-of-care testing (POCT) device (Rapidpoint Coag) with those from standard laboratory tests. The subjects were newborn infants needing coagulation screen for any clinical indications within a regional neonatal intensive care unit. The level of agreement between POCT and laboratory measurements of PT and APTT was determined. For PT: the bias was from -7.6 to 12.4 s and precision was 5.0 s. For the detection of prolonged PT at a level of 16 s, the sensitivity was 0.70, specificity was 0.57 and the positive predictive value (PPV) was 0.62. For APTT: the bias was from -39.1 to 23.7 s, and precision was 15.7 s. For the detection of prolonged APTT at a level of 55 s, the sensitivity was 0.80, specificity was 0.95 and the PPV was 0.80. The POCT device tested has limited utility as a cot-side device for screening for a prolongation of the APTT in the newborn but is not sensitive for screening for prolongation of the PT.

Does routine assessment and real-time feedback improve cancer patients' psychosocial well-being?

This study examined the effectiveness of giving medical oncologists immediate feedback about cancer patients' self-reported psychosocial well-being in reducing those patients' levels of anxiety, depression, perceived needs and physical symptoms. Cancer patients attending one cancer centre for their first visit were allocated to intervention (n = 42) or control (n = 38) groups. All patients completed a computerized survey assessing their psychosocial well-being while waiting to see the oncologist. Intervention patients' responses were immediately scored and summary reports were placed in each patient's file for follow-up. A total of 48 participants (25 intervention and 23 control) completed the survey four times. Intervention patients who reported a debilitating physical symptom at visit 2 were significantly less likely to report a debilitating physical symptom at visit 3 compared with control patients (OR = 2.8, P = 0.04). Reductions in levels of anxiety, depression and perceived needs among intervention patients were not significantly different to control patients. Repeated collection and immediate feedback of patient-reported health information to oncologists has potential to improve patients' symptom control, but has little impact upon emotional well-being, including those at high risk. Future research should consider providing the feedback to other health professionals and patients, and monitor the impact on the process of individual patient care.

Survey of paediatric complementary and alternative medicine use in health and chronic illness.

Groups of 25 children with cerebral palsy (CP), inflammatory bowel disease (IBD), and cancer were compared to 25 healthy children to establish use of complementary or alternative medicine (CAM). Children with chronic disease were greater than three times more likely to use CAM, usually without paediatricians' knowledge.

Effects of transfusion in anemia of prematurity.

The authors aimed to test the hypothesis that blood transfusions depress hematopoiesis in healthy infants with anemia of prematurity (AOP). They also set out to find markers that predict recovery from AOP. Thirty-nine premature babies underwent weekly and post-transfusion measurements of hemoglobin concentrations, reticulocyte counts (RCC), and erythropoietin levels (EPO). RCC and EPO dropped significantly 7 days after a blood transfusion but had normalized after 14 days. Elevated RCC or EPO levels were not predictive of an increase in hemoglobin. Postnatal HbFg/dL was higher in babies who had received transfusions. The authors conclude that blood transfusions depress erythropoiesis in infants with AOP and stimulate HbF synthesis but this effect is not sustained. Reticulocyte counts and erythropoietin levels are unhelpful in predicting recovery from AOP.

Clinical decision support systems for neonatal care.

BACKGROUND: Clinical decision support systems (CDSS) are computer-based information systems used to integrate clinical and patient information to provide support for decision-making in patient care. They may be useful in aiding the diagnostic process, the generation of alerts and reminders, therapy critiquing/planning, information retrieval, and image recognition and interpretation. CDSS for use in adult patients have been evaluated using randomised control trials and their results analysed in systematic reviews. There is as yet no systematic review on CDSS use in neonatal medicine. OBJECTIVES: To examine whether the use of clinical decision support systems has an effect on 1. the mortality and morbidity of newborn infants and 2. the performance of physicians treating them SEARCH STRATEGY: The standard search method of the Cochrane Neonatal Review Group was used. Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), MEDLINE (from 1966 to August 2004), EMBASE (1980-2004), CINAHL (1982 to August 2004) and AMED (1985 to August 2004). SELECTION CRITERIA: Randomised or quasi-randomised controlled trials which compared the effects of CDSS versus no CDSS in the care of newborn infants. Trials which compared CDSS against other CDSS were also considered. The eligible interventions were CDSS for computerised physician order entry, computerised physiological monitoring, diagnostic systems and prognostic systems. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility using a standard pro forma. Methodological quality was assessed independently by the different investigators. MAIN RESULTS: Two studies fitting the selection criteria were found for computer aided prescribing and one study for computer aided physiological monitoring.Computer-aided prescribing: one study (Cade 1997) examined the effects of computerised prescribing of parenteral nutrition ordering. No significant effects on short-term outcomes were found and longer term outcomes were not studied. The second study (Balaguer 2001) investigated the effects of a database program in aiding the calculation of neonatal drug dosages. It was found that the time taken for calculation was significantly reduced and there was a significant reduction in the number of calculation errors.Computer-aided physiological monitoring: one eligible study (Cunningham 1998) was found which examined the effects of computerised cot side physiological trend monitoring and display. There were no significant effects on mortality, volume of colloid infused, frequency of blood gases sampling (samples per day) or severe (Papile Grade 4) intraventricular haemorrhage. Published data did not permit us to analyse effects on long-term neurodevelopmental outcome. AUTHORS' CONCLUSIONS: There are very limited data from randomised trials on which to assess the effects of clinical decision support systems in neonatal care. Further evaluation of CDSS using randomised controlled trials is warranted.

A mathematical model of CO2 variation in the ventilated neonate.

A mathematical model of the variation of partial pressure of carbon dioxide in the arterial blood of a ventilated neonate is developed. The model comprises alveolar, arterial, pulmonary, venous and tissue compartments, with gas exchange in the lung determined by inspiration and expiration terms. Gas exchange is modelled through diffusion and convective transfer. Carbon dioxide is produced in the tissue by a metabolic term. Shunting is modelled by allowing blood flow to bypass the pulmonary compartment in which diffusion takes place. The model predicts changes in the carbon dioxide partial pressures that occur following abrupt changes in the ventilation settings, and show broad agreement with actual data obtained from novel sensing technology.

A 5-microm filter does not reduce propofol-induced pain.

We assessed the effectiveness of a 5-microm filter in reducing propofol-induced pain and determined whether any reduction is due to removal of contaminants or an alteration in flow characteristics. A total of 120 unpremedicated women (ASA 1-3, aged 18-70 yr) were randomly allocated to one of three equal-sized groups. In group A, propofol was drawn up and injected through an unfiltered plastic cannula. In group B, propofol was drawn up through a 5-microm filter needle and injected through an unfiltered plastic cannula. In group C, propofol was drawn up and injected through a 5-microm filter needle. Unmodified propofol from a 20-ml rubber topped vial at room temperature was used. A 22-g cannula was inserted into the largest visible vein on the dorsum of the non-dominant hand. Propofol was administered at 0.5 ml.s-1 and patients were asked about pain every 10 s until unresponsive, by a blinded observer. The pain score for the patient was the taken as the most severe pain documented. The frequency and severity of pain were similar among groups. We conclude that a 5-microm filter does not reduce pain associated with injection of propofol drawn from a vial with a rubber bung.

Diversity of ascomycete laccase gene sequences in a southeastern US salt marsh.

The diversity of ascomycete laccase sequences was surveyed in a southeastern US salt marsh using a degenerate primer set designed around copper binding sites conserved in fungal laccases. This gene was targeted for diversity analysis because of its potential function in lignin degradation in the salt marsh ecosystem and because few studies have assessed functional gene diversity in natural fungal communities. Laccase sequences were amplified from genomic DNA extracted from 24 isolates (representing 10 ascomycete species) cultured from decaying blades of Spartina alterniflora, and from DNA extracted directly from the decaying blades. Among the ascomycete isolates, 21 yielded a PCR product of expected size (900 bp) that was tentatively identified as laccase based on sequence similarities to previously published laccase sequences from related organisms. Overall, 13 distinct sequence types, containing 39 distinct sequences, were identified among the isolates, with several species yielding multiple distinct laccase types. PCR amplifications from early and late decay blades of S. alterniflora yielded seven laccase types. Of these, five were composed of sequences >96% similar at the amino acid level to sequences from three cultured ascomycetes previously found to be dominant members of the fungal communities on decaying S. alterniflora blades. Two of the laccase types from the natural-decay clone library were novel and did not match any of the sequences obtained from the cultured ascomycetes. The 39 distinct sequences and 15 distinct laccase sequence types retrieved from the S. alterniflora decay system demonstrate high sequence diversity of this functional gene in a natural fungal community.

Analysis of internal transcribed spacer (ITS) regions of rRNA genes in fungal communities in a southeastern U.S. salt marsh.

The ascomycete community colonizing decaying Spartina alterniflora blades in a southeastern U.S. salt marsh was characterized by analysis of internal transcribed spacer (ITS) regions of fungal rRNA genes. ITS sequences were amplified with ascomycete-specific primers from DNA extracted from S. alterniflora blades at two stages of decay (early and late) and were identified based on sequence analysis of a companion ascomycete culture collection. The S. alterniflora ITS libraries were dominated by clones from three species of ascomycetes: Mycosphaerella sp. 2, Phaeosphaeria spartinicola, and Phaeosphaeria halima. ITS sequences from five other less abundant ascomycete species were also found in the clone libraries, only two of which could be identified based on the culture collection, Hydropisphaera erubescens and a new species nicknamed '4clt'. Ascospore expulsion assays indicated dominance by the same three species as the ITS analysis, although this non-molecular approach differed from the molecular method in relative ranking of the dominant species and in characterization of minor species. Analysis of ITS amplicons from three replicate plots by terminal restriction fragment length polymorphism (T-RFLP) analysis showed significant spatial homogeneity in ascomycete community composition for both early- and late-stage decay. ITS sequence analysis identified morphologically cryptic subgroups for two of the three dominant salt marsh ascomycetes.

Randomized controlled study of digestive enzyme activity following trophic feeding.

UNLABELLED: A randomized, controlled, prospective study of 80 preterm infants of birthweight less than 1750 g requiring ventilatory support was performed. While ventilatory support was required group TF (39 infants) received trophic feeding (0.5-1 ml h(-1)) along with parenteral nutrition, whereas group C (41 infants) received parenteral nutrition alone. When ventilatory support was no longer required milk feeds were started in group C and then increased in both groups until full milk feeds were established. The ratio of lactase to sucrase activity (L:S ratio) was measured in aspirated proximal intestinal fluid on 3 occasions: immediately after ventilatory support was withdrawn (T0), 7 days later (T7) and 14 days later (T14). On the same 3 occasions faecal chymotrypsin activity was measured. The mean difference (95% confidence interval) L:S ratio was significantly higher in group TF at both T0 and T14, 1.8 (0.03, 3.57) and 0.78 (0.2, 1.35) U l(-1), respectively. There was no significant difference in faecal chymotrypsin concentration. CONCLUSION: Trophic feeding alters relative intestinal disaccharidase activity, probably by inducing lactase production, but has no effect on pancreatic chymotrypsin activity.