Prospective evaluation of three point of care devices for glycemia measurement in a neonatal intensive care unit.

Hypoglycemia, if recurrent, may have severe consequences on cognitive and psychomotor development of neonates. Therefore, screening for hypoglycemia is a daily routine in every facility taking care of newborn infants. Point-of-care-testing (POCT) devices are interesting for neonatal use, as their handling is easy, measurements can be performed at bedside, demanded blood volume is small and results are readily available. However, such whole blood measurements are challenged by a wide variation of hematocrit in neonates and a spectrum of normal glucose concentration at the lower end of the test range. We conducted a prospective trial to check precision and accuracy of the best suitable POCT device for neonatal use from three leading companies in Europe. Of the three devices tested (Precision Xceed, Abbott; Elite XL, Bayer; Aviva Nano, Roche), Aviva Nano exhibited the best precision. None completely fulfilled the ISO-accuracy-criteria 15197: 2003 or 2011. Aviva Nano fulfilled these criteria in 92% of cases while the others were <87%. Precision Xceed reached the 95% limit of the 2003 ISO-criteria for values ≤4.2 mmol/L, but not for the higher range (71%). Although validated for adults, new POCT devices need to be specifically evaluated on newborn infants before adopting their routine use in neonatology.

Could Hyperglycaemia and Troponin I predict outcome in intensive care after congenital heart surgery in children?

Objective: To establish if hyperglycaemia and cardiac Troponin I (cTnI) after congenital heart surgery on cardiopulmonary bypass in children could predict outcome in intensive care unit. Methods: retrospective cohort study including 274 children (mean age 4.6 years; range 0 - 17 years-old). CTnI and glucose values were retrieved from our database. Integrated values (area under the curve (AUC)) were calculated for evaluation of sustained hyperglycaemia and then normalised per hour (48h-Gluc/h). Maximal cTnI, fi rst glucose value (Gluc1) and 48h-Gluc/h were then correlated with duration of mechanical ventilation, ICU stay and mortality using cut-off values. Results: The mean duration of mechanical ventilation was 5.1 ± 7.2 days and ICU stay was 11.0 ± 13.3 days, 11 patients (3.9%) died. Hyperglycaemia (>6.1 mmol/l) was present in 68% of children at admission and was sustained in 85% for 48 hours. The mean value of Gluc1 (7.3 ± 2.7 vs. 11.8 ± 6.4 mmol/l, p < 0.0001), 48h-Gluc/h (7.4 ± 1.4 vs. 9.9 ± 4.6 mmol/l/h, p < 0.0001) and cTnI max (16.7 ± 21.8 vs. 59.2 ± 41.4 mcg/l, p < 0.0001) were signifi cantly lower in survivors vs. non survivors. Cut-off values and odds ratio are summarised in Table 1. Analyses for duration of mechanical ventilation and for length of stay in ICU are depicted in Table 2. Conclusions: Hyperglycaemia is frequent after cardiopulmonary bypass and sustained in the fi rst 48 hours. Admission glycaemia and cTnI max are associated with a high risk of mortality, prolonged duration of mechanical ventilation and prolonged length of stay in ICU.

Facteurs Influençant la Progression du Score EDSS dans la Sclérose en Plaques Récurrente-Rémittente

Introduction : la Sclérose en plaques (SEP) est le prototype de désordre auto-immun du système nerveux central. Avec environ 110 malades par 100'000 habitants, la Suisse est considérée un pays à haute prévalence. Chez environ 80% des patients, la maladie débute par la forme récurrente- rémittente (RR), où des poussées aiguës s'intercalent avec des périodes de rémission. Cette phase se conclut dans son évolution naturelle généralement en une phase secondairement progressive, pendant laquelle le déficit progresse en l'absence de poussée. Sur le plan physiopathologique, deux phénomènes interagissent : l'atteinte inflammatoire démyélinisante et l'atteinte neurodégénerative. La première est { l'origine des poussées aiguës, la deuxième se manifeste cliniquement par la progression irréversible du déficit neurologique. En Suisse les immunomodulateurs ont été utilisés comme thérapies de fond pour la SEP à partir des années 1995. Leur effet sur le taux de poussées a été largement démontré, tandis que leur efficacité sur l'évolution de la maladie à long terme reste ouverte. Le moyen le plus répandu pour quantifier le niveau du handicap neurologique est la Kurtzke Expanded Disability Status Scale (EDSS). Cette échelle évalue les troubles neurologiques en les classifiant de 0 (examen normal) à 10 (décès) avec des marches de demi-points. Notre recherche à voulu identifier des facteurs cliniques précoces { valeur prédictif sur l'évolution du déficit neurologique permanent, ainsi qu'analyser le moment d'introduction du traitement pour extraire des informations utiles { la décision thérapeutique. Méthodes : Exploitation de la base de données iMed-CHUV comptant 1150 patients SEP (dont 622 SEP RR) pour analyser rétrospectivement, dans la SEP RR, l'influence de différentes variables cliniques précoces (taux de poussées pendant les premières deux années de maladie, intervalle entre les deux premières poussées, sévérité et site anatomique de la première poussée, déficit résiduel après la première poussée) et de deux caractéristiques liées { l'instauration du traitement immunosuppresseur de fond (âge et délai d'introduction) sur l'évolution du déficit neurologique vers un score EDSS ≥4.0. Les variables ont été testées avec la méthode d'estimation de taux de survie Kaplan-Meier. Résultats: 349 patients avec SEP RR possédaient les critères nécessaires pour faire partie de l'analyse, le suivi moyen étant de 8.26 ans (SD 4.77). Un taux de poussées élevé pendant les premiers 2 ans (>1 vs ≤1) et un long intervalle entre les 2 premiers épisodes (>36 vs >12-36 vs ≤12) étaient significativement associés au risque de progression du déficit neurologique vers un score EDSS de 4.0 ou plus (log Rank P=0.016 et P=0.008 respectivement). Par contre ni le site anatomique de la première poussée ni l'âge d'introduction du traitement immunomodulateur n'avaient d'influence significative sur la progression du déficit neurologique (log rank P=0.370 et P=0.945 respectivement). Etonnamment une introduction rapide du traitement était associée à une plus forte progression du déficit neurologique (log rank P=0.032), montrant qu'une partie des patients a une évolution bénigne même en l'absence de traitement. Conclusions : L'activité inflammatoire précoce, dont le niveau peut être estimé par indices précoces comme le taux de poussées et l'intervalle entre les deux premières poussées, mais non le site de primo-manifestation prédit la progression ultérieure du déficit neurologique. Ces indices doivent être utilisés en combinaison avec les informations fournies par l'IRM pour l'individuation et le traitement précoce des patients à risque, indépendamment de leur âge. En raison des effets indésirables et des coûts élevés, les thérapies doivent cibler de façon spécifique les classes à risque, et épargner les patients avec évolution lente.

Assessing the value of CAN-gene mutations using MALDI-TOF MS.

PURPOSE: To identify cancer-linked genes, Sjöblom et al. and Wood et al. performed a genome-wide mutation screening in human breast and colorectal cancers. 140 CAN-genes were found in breast cancer, which in turn contained overall 334 mutations. These mutations could prove useful for diagnostic and therapeutic purposes. METHODS: We used a MALDI-TOF MS 40-plex assay for testing 40 loci within 21 high-ranking breast cancer CAN-genes. To confirm mutations, we performed single-plex assays and sequencing. RESULTS: In general, the mutation rate of the analyzed loci in our sample cohort was very low. No mutation from the 40 loci analyzed could be found in the 6 cell lines. In tissue samples, a single breast cancer tissue sample showed heterozygosity at locus c.5834G>A within the ZFYVE26 gene (Zinc finger FYVE domain-containing gene 26). CONCLUSIONS: Sjöblom et al./Wood et al. already showed that the vast majority of CAN-genes are mutated at very low frequency. Due to the fact that we only found one mutation in our cohort, we therefore assume that at the selected loci, mutations might be low-frequency events and therefore, more rarely detectable. However, further evaluation of the CAN-gene mutations in larger cohorts should be the aim of further studies.

Major impact of body position on arterial stiffness indices derived from radial applanation tonometry in pregnant and nonpregnant women.

OBJECTIVE: To evaluate the impact of body position on the arterial stiffness indices provided by radial applanation tonometry in pregnant and nonpregnant women. METHODS: Twenty-four young women (18-30 years) in the third trimester of a normal pregnancy and 20 healthy nonpregnant women of the same age were enrolled. In each, applanation tonometry was carried out in the sitting and supine position. The following stiffness indices were analyzed: systolic augmentation index (sAix), sAix adjusted for heart rate (sAix@75) and diastolic augmentation index (dAix), all expressed in % of central aortic pulse pressure. RESULTS: The sAix was apparently not influenced by body position, but the transition from seated to supine was associated with a substantial decrease in heart rate. When correcting for this confounder by calculating the sAix@75, systolic augmentation was substantially lower when individuals were supine (mean ± SD: nonpregnant 3.0 ± 14.4%, pregnant 8.8 ± 9.7%) than when they were sitting (nonpregnant 5.7 ± 13.0%, pregnant 11.1 ± 83%, P = 0.005 supine vs. seated in both study groups, P > 0.2 for pregnant vs. nonpregnant). The influence of body position on the dAix went in the opposite direction (supine: nonpregnant 9.7 ± 6.6%, pregnant 4.4 ± 3.5%; seated: nonpregnant 7.7 ± 5.8%, pregnant 3.3 ± 2.4%, P < 0.00001 supine vs. seated in both study groups, P = 0.001 for pregnant vs. nonpregnant). CONCLUSION: Body position has a major impact on the pattern of central aortic pressure augmentation by reflected waves in healthy young women examined either during third trimester pregnancy or in the nonpregnant state.

Assessing multiple sclerosis activity: is the in vitro production of tumor necrosis factor-alpha, interleukins 2, 6, 4, and 10, and immunoglobulin G of value?

Tumor necrosis factor (TNF) alpha, interleukins (IL) 2, 4, 6, and 10, and IgG oligoclonal bands (IgG OB) in vitro production was assessed, after whole-blood stimulation with lipopolysaccharide or concanavalin A, in 61 patients presenting with relapsing-remitting, relapsing-progressive, or chronic progressive multiple sclerosis. Multiple sclerosis patients were receiving no treatment or azathioprine (AZA), cyclosporin, cyclophosphamide, subcutaneous interferon (IFN) beta 1 a, or corticosteroids (CST). Statistical correlations significantly showed that: (a) AZA lowers TNF-alpha (P = 0.002) and increases IL-4 production (P = 0.0024), and IFN-beta 1 a increases TNF-alpha and decreases IL-4 levels; (b) CST has a negative effect on TNF-alpha, IL-6, and IL-4 synthesis; and (c) AZA, IFN-beta 1 a, and CST diminish IgG OB synthesis (P = 0.001). Although our study of the dynamics of TNF-alpha, IL-2, IL-4, IL-6, and IL-10 in vitro production generally found no statistically significant correlations (partly explained by the limited number of values in the various groups), IL-6 was shown to drop during the periods surrounding relapse (P = 0.05) in the absence of treatment, while TNF-alpha (P = 0.04) and IL-6 (P < 0.05) dropped before exacerbation in the presence of AZA. In vitro production of TNF-alpha was closely and positively correlated with that of IL-6, independently of clinical features. The enhanced production of IL-10 detected before or at relapse with AZA and IFN-beta 1 a (trends) may interfere with initiation of the immune reaction and with the development of new CNS lesions. Some discrepancies with previously published results stress the difficulties in studying the state of stimulation of different populations of leukocytes by using a variety of in vitro stimuli and in establishing a correlation between mRNA studies and the amount of final or active protein produced.

Format of medical order sheet improves security of antibiotics prescription: The experience of an intensive care unit.

OBJECTIVE: To assess whether formatting the medical order sheet has an effect on the accuracy and security of antibiotics prescription. DESIGN: Prospective assessment of antibiotics prescription over time, before and after the intervention, in comparison with a control ward. SETTING: The medical and surgical intensive care unit (ICU) of a university hospital. PATIENTS: All patients hospitalized in the medical or surgical ICU between February 1 and April 30, 1997, and July 1 and August 31, 2000, for whom antibiotics were prescribed. INTERVENTION: Formatting of the medical order sheet in the surgical ICU in 1998. MEASUREMENTS AND MAIN RESULTS: Compliance with the American Society of Hospital Pharmacists' criteria for prescription safety was measured. The proportion of safe orders increased in both units, but the increase was 4.6 times greater in the surgical ICU (66% vs. 74% in the medical ICU and 48% vs. 74% in the surgical ICU). For unsafe orders, the proportion of ambiguous orders decreased by half in the medical ICU (9% vs. 17%) and nearly disappeared in the surgical ICU (1% vs. 30%). The only missing criterion remaining in the surgical ICU was the drug dose unit, which could not be preformatted. The aim of antibiotics prescription (either prophylactic or therapeutic) was indicated only in 51% of the order sheets. CONCLUSIONS: Formatting of the order sheet markedly increased security of antibiotics prescription. These findings must be confirmed in other settings and with different drug classes. Formatting the medical order sheet decreases the potential for prescribing errors before full computerized prescription is available.

The role of energy and nutritional support in the intensive care unit.

Malnutrition is common in critically ill, hospitalized patients and so represents a major problem for intensive care. Nutritional support can be beneficial in such cases and may help preserve vital organ and immune function. Energy requirements, route of delivery and potential complications of nutritional support are discussed in this paper.

Leukemic cluster growth in culture is an independent risk factor for acute myeloid leukemia and short survival in patients with myelodysplastic syndrome

In patients with myelodysplastic syndrome (MDS) precursor cell cultures (colony-forming unit cells, CFU-C) can provide an insight into the growth potential of malignant myeloid cells. In a retrospective single-center study of 73 untreated MDS patients we assessed whether CFU-C growth patterns were of prognostic value in addition to established criteria. Abnormalities were classified as qualitative (i.e. leukemic cluster growth) or quantitative (i.e. strongly reduced/absent growth). Thirty-nine patients (53%) showed leukemic growth, 26 patients (36%) had strongly reduced/absent colony growth, and 12 patients showed both. In a univariate analysis the presence of leukemic growth was associated with strongly reduced survival (at 10 years 4 vs. 34%, p = 0.004), and a high incidence of transformation to AML (76 vs. 32%, p = 0.01). Multivariate analysis identified leukemic growth as a strong and independent predictor of early death (relative risk 2.12, p = 0.03) and transformation to AML (relative risk 2.63, p = 0.04). Quantitative abnormalities had no significant impact on the disease course. CFU- C assays have significant predictive value in addition to established prognostic factors in MDS. Leukemic growth identifies a subpopulation of MDS patients with poor prognosis.