Development and current use of parenteral nutrition in critical care - an opinion paper.

Critically ill patients depend on artificial nutrition for the maintenance of their metabolic functions and lean body mass, as well as for limiting underfeeding-related complications. Current guidelines recommend enteral nutrition (EN), possibly within the first 48 hours, as the best way to provide the nutrients and prevent infections. EN may be difficult to realize or may be contraindicated in some patients, such as those presenting anatomic intestinal continuity problems or splanchnic ischemia. A series of contradictory trials regarding the best route and timing for feeding have left the medical community with great uncertainty regarding the place of parenteral nutrition (PN) in critically ill patients. Many of the deleterious effects attributed to PN result from inadequate indications, or from overfeeding. The latter is due firstly to the easier delivery of nutrients by PN compared with EN increasing the risk of overfeeding, and secondly to the use of approximate energy targets, generally based on predictive equations: these equations are static and inaccurate in about 70% of patients. Such high uncertainty about requirements compromises attempts at conducting nutrition trials without indirect calorimetry support because the results cannot be trusted; indeed, both underfeeding and overfeeding are equally deleterious. An individualized therapy is required. A pragmatic approach to feeding is proposed: at first to attempt EN whenever and as early as possible, then to use indirect calorimetry if available, and to monitor delivery and response to feeding, and finally to consider the option of combining EN with PN in case of insufficient EN from day 4 onwards.

Kangaroo mother care diminishes pain from heel lance in very preterm neonates: a crossover trial.

BACKGROUND: Skin-to-skin contact, or kangaroo mother care (KMC) has been shown to be efficacious in diminishing pain response to heel lance in full term and moderately preterm neonates. The purpose of this study was to determine if KMC would also be efficacious in very preterm neonates. METHODS: Preterm neonates (n = 61) between 28 0/7 and 31 6/7 weeks gestational age in three Level III NICU's in Canada comprised the sample. A single-blind randomized crossover design was employed. In the experimental condition, the infant was held in KMC for 15 minutes prior to and throughout heel lance procedure. In the control condition, the infant was in prone position swaddled in a blanket in the incubator. The primary outcome was the Premature Infant Pain Profile (PIPP), which is comprised of three facial actions, maximum heart rate, minimum oxygen saturation levels from baseline in 30-second blocks from heel lance. The secondary outcome was time to recover, defined as heart rate return to baseline. Continuous video, heart rate and oxygen saturation monitoring were recorded with event markers during the procedure and were subsequently analyzed. Repeated measures analysis-of-variance was employed to generate results. RESULTS: PIPP scores at 90 seconds post lance were significantly lower in the KMC condition (8.871 (95%CI 7.852-9.889) versus 10.677 (95%CI 9.563-11.792) p < .001) and non-significant mean differences ranging from 1.2 to1.8. favoring KMC condition at 30, 60 and 120 seconds. Time to recovery was significantly shorter, by a minute(123 seconds (95%CI 103-142) versus 193 seconds (95%CI 158-227). Facial actions were highly significantly lower across all points in time reaching a two-fold difference by 120 seconds post-lance and heart rate was significantly lower across the first 90 seconds in the KMC condition. CONCLUSION: Very preterm neonates appear to have endogenous mechanisms elicited through skin-to-skin maternal contact that decrease pain response, but not as powerfully as in older preterm neonates. The shorter recovery time in KMC is clinically important in helping maintain homeostasis. TRIAL REGISTRATION: (Current Controlled Trials) ISRCTN63551708.

Large-scale imatinib dose-concentration-effect study in CML patients under routine care conditions.

This observational study analyzed imatinib pharmacokinetics and response in 2478 chronic myeloid leukemia (CML) patients. Data were obtained through centralized therapeutic drug monitoring (TDM) at median treatment duration of ≥2 years. First, individual initial trough concentrations under 400mg/day imatinib starting dose were estimated. Second, their correlation (C^min(400mg)) with reported treatment response was verified. Low imatinib levels were predicted in young male patients and those receiving P-gp/CYP3A4 inducers. These patients had also lower response rates (7% lower 18-months MMR in male, 17% lower 1-year CCyR in young patients, Kaplan-Meier estimates). Time-point independent multivariate regression confirmed a correlation of individual C^min(400mg) with response and adverse events. Possibly due to confounding factors (e.g. dose modifications, patient selection bias), the relationship seemed however flatter than previously reported from prospective controlled studies. Nonetheless, these observational results strongly suggest that a subgroup of patients could benefit from early dosage optimization assisted by TDM, because of lower imatinib concentrations and lower response rates.

IL28B polymorphism is significantly correlated with ifn anti-viral effectiveness already on first day of pegylated interferon-alpha and ribavirin therapy of chronic HCV infection

Background and Aims: Recently, single nucleotide polymorphisms (SNPs) in IL28B were shown to correlate with response to pegylated interferon-a (IFN) and ribavirin therapy of chronic HCV infection. However, the cause for the SNPs effect on therapy response and its application for direct anti-viral (DAV) treatment are not clear. Here, we analyze early HCV kinetics as function of IL28B SNPs to determine its specific effect on viral dynamics. Methods: IL28B SNPs rs8099917, rs12979860 and rs12980275 were genotyped in 252 chronically HCV infected Caucasian naïve patients (67% HCV genotype 1, 28% genotype 2-3) receiving peginterferonalfa- 2a (180 mg/qw) plus ribavirin (1000-1200 mg/qd) in the DITTO study. HCV-RNA was measured (LD = 50 IU/ml) frequently during first 28 days. Results: RVR was achieved in 33% of genotype 1 patients with genotype CC at rs12979860 versus 12-16% for genotypes TT and CT (P < 0.03). Significant (P < 0.001) difference in viral decline was observed already at day 1 (see Figure). First phase decline was significantly (P < 0.001) larger in patients with genotype CC (2.0 log) than for TT and CT genotypes (0.6 and 0.8), indicating IFN anti-viral effectiveness in blocking virion production of 99% versus 75-84%. There was no significant association between second phase slope and rs12979860 genotype in patients with a first phase decline larger than 1 log. HCV kinetics as function of IL28b SNP. The same trend (not shown) was observed for HCV genotype 2-3 patients with different SNP genotype distribution that may indicate differential selection pressure as function of HCV genotype. Similar results were observed for SNPs rs8099917 and rs12980275, with a strong linkage disequilibrium among the 3 loci allowing to define the composite haplotype best associated with IFN effectiveness. Conclusions: IFN effectiveness in blocking virion production/ release is strongly affected by IL28B SNPs, but not other viral dynamic properties such as infected cell loss rate. Thus, IFN based therapy, as standard-of-care or in combination with DAV, should consider IL28B SNPs for prediction and personalized treatment, while response to pure DAV treatment may be less affected by IL28B SNPs. Additional analyses are undergoing to pinpoint the SNP effect on IFN anti-viral effectiveness.

Nouveautés en médecine ambutatoire: dépistage, traitement et iatrogénicité [Innovations in ambulatory care: screening, treatment and iatrogenicity]

Cette année, six études utiles pour la pratique ont été retenues. L'indication à la mammographie entre 40 et 49 ans devrait être évaluée individuellement et en tenant compte des risques/bénéfices de cet examen. Au-delà de 65 ans, un dépistage systématique de la fibrillation auriculaire avec prise de pouls puis ECG (si pouls irrégulier) pourrait être réalisé de manière systématique. Les risques de complications postcolonoscopie existent, particulièrement suite à des biopsies/polypectomies, et ce risque devrait être discuté. Les inhibiteurs de la pompe à protons au long court sont un facteur de risque de fracture de hanche. S'il est important de prendre en charge des pressions artérielles élevées au-delà de 80 ans, il faut être prudent (orthostatisme). Une corticothérapie précoce suite à une paralysie faciale périphérique est efficace. This year we have selected six studies useful for the day to day practice. A mammography in women 40 to 49 years of age should be evaluated taking into account the patient's profile and the possible risks and benefits of this exam. In patients over 65 years of age, a systematic atrial fibrillation screening, with pulse rate measuring then ECG (if irregular beat) should be realised on a regular basis. The risks for complications following colonoscopies do exist, especially after biopsies/polypectomies and this risk should be discussed. Long term proton pump inhibitor treatment is a risk factor for hip fracture. It is important to treat high blood pressure problems in the elderly, but the orthostatic risks should be adressed. A corticoid treatment started quickly for Bell's palsy is efficient

Quantifying uncertainty: physicians' estimates of infection in critically ill neonates and children.

To determine the diagnostic accuracy of physicians' prior probability estimates of serious infection in critically ill neonates and children, we conducted a prospective cohort study in 2 intensive care units. Using available clinical, laboratory, and radiographic information, 27 physicians provided 2567 probability estimates for 347 patients (follow-up rate, 92%). The median probability estimate of infection increased from 0% (i.e., no antibiotic treatment or diagnostic work-up for sepsis), to 2% on the day preceding initiation of antibiotic therapy, to 20% at initiation of antibiotic treatment (P&lt;.001). At initiation of treatment, predictions discriminated well between episodes subsequently classified as proven infection and episodes ultimately judged unlikely to be infection (area under the curve, 0.88). Physicians also showed a good ability to predict blood culture-positive sepsis (area under the curve, 0.77). Treatment and testing thresholds were derived from the provided predictions and treatment rates. Physicians' prognoses regarding the presence of serious infection were remarkably precise. Studies investigating the value of new tests for diagnosis of sepsis should establish that they add incremental value to physicians' judgment.

A dynamic assessment of medication-taking behavior during pregnancy and postpartum: should cART adherence be reinforced during postpartum?

This study compared adherence (persistence and execution) during pregnancy and postpartum in HIV-positive women having taken part in the adherence-enhancing program of the Community Pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne between 2004 and 2012. This interdisciplinary program combined electronic drug monitoring and semi-structured, repeated motivational interviews. This was a retrospective, observational study. Observation period spread over from first adherence visit after last menstruation until 6 months after childbirth. Medication-taking was recorded by electronic drug monitoring. Socio-demographic and delivery data were collected from Swiss HIV Cohort database. Adherence data, barriers and facilitators were collected from pharmacy database. Electronic data were reconciled with pill-count and interview notes in order to include reported pocket-doses. Execution was analyzed over 3-day periods by a mixed effect logistic model, separating time before and after childbirth. This model allowed us to estimate different time slopes for both periods and to show a sudden fall associated with childbirth. Twenty-five pregnant women were included. Median age was 29 (IQR: 26.5, 32.0), women were in majority black (n_17,68%) and took a cART combining protease and nucleoside reverse transcriptase inhibitors (n_24,96%). Eleven women (44%) were ART-naı¨ve at the beginning of pregnancy. Twenty women (80%) were included in the program because of pregnancy. Women were included at all stages of pregnancy. Six women (24%) stopped the program during pregnancy, 3 (12%) at delivery, 4 (16%) during postpartum and 12 (48%) stayed in program at the end of observation time. Median number of visits was 4 (3.0, 6.3) during pregnancy and 3 (0.8, 6.0) during postpartum. Execution was continuously high during pregnancy, low at beginning of postpartum and increased gradually during the 6 months of postpartum. Major barriers to adherence were medication adverse events and difficulties in daily routine. Facilitators were motivation for promoting child-health and social support. The dramatic drop and very slow increase in cART adherence during postpartum might result in viral rebound and drug resistance. Although much attention is devoted to pregnant women, interdisciplinary care should also be provided to women in the community during first trimester of postpartum to support them in sustaining cART adherence.

Zerebrale Probleme in der pädiatrischen Intensivmedizin [Cerebral problems in pediatric intensive care]

This paper presents a review of different methods enabling the monitoring of cerebral function in neonatal and paediatric intensive care. EEG, evoked potentials, conventional radiological studies, computerized tomography, ultrasound, intracranial pressure measurements, nuclear magnetic resonance, Doppler ultrasound, radioisotope studies, angiography, infra-red spectral analysis and last, but not least, clinical examination produce information regarding the neurological state of the patient which must be critically analysed in order to ensure optimal management of the case. Unfortunately, and in spite of impressive progress in non-invasive monitoring of the cerebral function, we are still forced to make important medical and ethical decisions without precise information about the neurological state of our patients.

Access to specialized pediatric cancer care in Switzerland.

BACKGROUND: Specialized pediatric cancer centers (PCCs) are thought to be essential to obtain state-of-the-art care for children and adolescents. We determined the proportion of childhood cancer patients not treated in a PCC, and described their characteristics and place of treatment. PROCEDURE: The Swiss Childhood Cancer Registry (SCCR) registers all children treated in Swiss PCCs. The regional cancer registries (covering 14/26 cantons) register all cancer patients of a region. The children of the SCCR with data from 7 regions (11 cantons) were compared, using specialized software for record linkage. All children <16 years of age at diagnosis with primary malignant tumors, diagnosed between 1990 and 2004, and living in one of these regions were included in the analysis. RESULTS: 22.1% (238/1,077) of patients recorded in regional registries were not registered in the SCCR. Of these, 15.7% (169/1,077) had never been in a PCC while 6.4% (69/1,077) had been in a PCC but were not registered in the SCCR, due to incomplete data flow. In all diagnostic groups and in all age groups, a certain proportion of children was treated outside a PCC, but this proportion was largest in children suffering from malignant bone tumors/soft tissue sarcomas and from malignant epithelial neoplasms, and in older children. The proportion of patients treated in a PCC increased over the study period (P < 0.0001). CONCLUSIONS: One in six childhood cancer patients in Switzerland was not treated in a PCC. Whether these patients have different treatment outcomes remained unclear.

Use of antibiotics in pediatric intensive care and potential savings.

OBJECTIVE: Minimizing unwarranted prescription of antibiotics remains an important objective. Because of the heterogeneity between units regarding patient mix and other characteristics, site-specific targets for reduction must be identified. Here we present a model to address the issue by means of an observational cohort study. SETTING: A tertiary, multidisciplinary, neonatal, and pediatric intensive care unit of a university teaching hospital. PATIENTS: All newborns and children present in the unit (n = 456) between September 1998 and March 1999. Reasons for admission included postoperative care after cardiac surgery, major neonatal or pediatric surgery, severe trauma, and medical conditions requiring critical care. METHODS: Daily recording of antibiotics given and of indications for initiation. After discontinuation, each treatment episode was assessed as to the presence or absence of infection. RESULTS: Of the 456 patients 258 (56.6%) received systemic antibiotics, amounting to 1815 exposure days (54.6%) during 3322 hospitalization days. Of these, 512 (28%) were prescribed as prophylaxis and 1303 for suspected infection. Treatment for suspected ventilator-associated pneumonia accounted for 616 (47%) of 1303 treatment days and suspected sepsis for 255 days (20%). Patients were classified as having no infection or viral infection during 552 (40%) treatment days. The average weekly exposure rate in the unit varied considerably during the 29-week study period (range: 40-77/100 hospitalization days). Patient characteristics did not explain this variation. CONCLUSION: In this unit the largest reduction in antibiotic treatment would result from measures assisting suspected ventilator-associated pneumonia to be ruled out and from curtailing extended prophylaxis.

Blood glucose level on postoperative day 1 is predictive of adverse outcomes after cardiovascular surgery

AIM: Hyperglycaemia is now a recognized predictive factor of morbidity and mortality after coronary artery bypass grafting (CABG). For this reason, we aimed to evaluate the postoperative management of glucose control in patients undergoing cardiovascular surgery, and to assess the impact of glucose levels on in-hospital mortality and morbidity. METHODS: This was a retrospective study investigating the association between postoperative blood glucose and outcomes, including death, post-surgical complications, and length of stay in the intensive care unit (ICU) and in hospital. RESULTS: A total of 642 consecutive patients were enrolled into the study after cardiovascular surgery (CABG, carotid endarterectomy and bypass in the lower limbs). Patients' mean age was 68+/-10 years, and 74% were male. In-hospital mortality was 5% in diabetic patients vs 2% in non-diabetic patients (OR: 1.66, P=0.076). Having blood glucose levels in the upper quartile range (> or =8.8 mmol/L) on postoperative day 1 was independently associated with death (OR: 10.16, P=0.0002), infectious complications (OR: 1.76, P=0.04) and prolonged ICU stay (OR: 3.10, P<0.0001). Patients presenting with three or more hypoglycaemic episodes (<4.1 mmol/L) had increased rates of mortality (OR: 9.08, P<0.0001) and complications (OR: 8.57, P<0.0001). CONCLUSION: Glucose levels greater than 8.8 mmol/L on postoperative day 1 and having three or more hypoglycaemic episodes in the postoperative period were predictive of mortality and morbidity among patients undergoing cardiovascular surgery. This suggests that a multidisciplinary approach may be able to achieve better postoperative blood glucose control. Conclusion: Objectif: L'hyperglycémie a été reconnue comme facteur prédictif de morbidité et mortalité après un pontage aortocoronaire. Notre étude avait pour objectif d'évaluer la prise en charge postopératoire des glycémies chez les patients qui avaient subi une intervention chirurgicale cardiovasculaire et d'évaluer l'impact de ces glycémies sur la mortalité et la morbidité intrahospitalières. Méthodes: Étude rétrospective recherchant une association entre la glycémie postopératoire et les complications postchirurgicales, la mortalité et la durée du séjour aux soins intensifs et à l'hôpital. Résultats: L'étude a été réalisée sur 642 patients qui avaient subi une intervention chirurgicale cardiovasculaire (ex. pontage aortocoronaire, endartérectomie de la carotide, pontage artériel des membres inférieurs). L'âge moyen est de 68 ± 10 ans et 74 % des patients étaient de sexe masculin. La mortalité intrahospitalière a été de 5 % parmi les patients diabétiques et 2 % chez les non-diabétiques (OR 1,66, p = 0,076). Les taux de glycémies situés dans le quartile supérieur (≥ 8,8 mmol/l) à j1 postopératoire sont associés de manière indépendante avec la mortalité (OR 10,16, 95 % CI 3,20-39,00, p = 0,0002), les complications infectieuses (OR 1,76, 95 % CI 1,02-3,00, p = 0,04) et la durée du séjour aux soins intensifs (OR 3,10, 95 % CI 1,83-5,38, p < 0,0001). Les patients qui avaient présenté trois hypoglycémies ou plus (< 4,1 mmol/l) ont présenté un taux augmenté de mortalité (OR 9,08, p ≤ 0,0001) et de complications (OR 8,57, p < 0,0001). Conclusion : Des glycémies supérieures à 8,8 mmol/l à j1 postopératoire et la présence de trois hypoglycémies ou plus en période postopératoire sont des facteurs prédictifs de mauvais pronostic chez les patients qui avaient subi une intervention chirurgicale cardiovasculaire. Ainsi, une approche multidisciplinaire devrait être proposée afin d'obtenir un meilleur contrôle postopératoire des glycémies.

A palliative care needs assessment for children

The development of a children’s hospice is not seen as a priority by the respondents in this study, some of whom raised concerns regarding accessibility and cost. There is a degree of ambiguity however, regarding the role of ‘hospice’ in paediatric palliative care with some respondents associating it only with end-of-life care. There is a substantial need for ongoing education, training and development of healthcare professionals caring for children with life-limiting conditions. Palliative care services currently provided to children in Ireland with life-limiting conditions are seen to be inequitable, differing significantly according to diagnosis (malignant versus nonmalignant) and according to geographic location. This poses challenges, particularly for parents of children with non-malignant diseases. Both families and professionals often deem the physical environment for adolescents in hospitals unsuitable. The difficulties encountered in the transition from children’s services to adult services have been identified as an issue for adolescents. The provision of bereavement support varies between services. Professionals have identified the need for a broader range of bereavement services.