Comparison of oxidative stress markers in HIV-infected patients on efavirenz or atazanavir/ritonavir-based therapy.

INTRODUCTION Chronic low-grade inflammation and immune activation may persist in HIV patients despite effective antiretroviral therapy (ART). These abnormalities are associated with increased oxidative stress (OS). Bilirubin (BR) may have a beneficial role in counteracting OS. Atazanavir (ATV) inhibits UGT1A1, thus increasing unconjugated BR levels, a distinctive feature of this drug. We compared changes in OS markers in HIV patients on ATV/r versus efavirenz (EFV)-based first-line therapies. MATERIALS AND METHODS Cohort of the Spanish Research Network (CoRIS) is a multicentre, open, prospective cohort of HIV-infected patients naïve to ART at entry and linked to a biobank. We identified hepatitis C virus/hepatitis B virus (HCV/HBV) negative patients who started first-line ART with either ATV/r or EFV, had a baseline biobank sample and a follow-up sample after at least nine months of ART while maintaining initial regimen and being virologically suppressed. Lipoprotein-associated Phospholipase A2 (Lp-PLA2), Myeloperoxidase (MPO) and Oxidized LDL (OxLDL) were measured in paired samples. Marker values at one year were interpolated from available data. Multiple imputations using chained equations were used to deal with missing values. Change in the OS markers was modelled using multiple linear regressions adjusting for baseline marker values and baseline confounders. Correlations between continuous variables were explored using Pearson's correlation tests. RESULTS 145 patients (97 EFV; 48 ATV/r) were studied. Mean (SD) baseline values for OS markers in EFV and ATV/r groups were: Lp-PLA2 [142.2 (72.8) and 150.1 (92.8) ng/mL], MPO [74.3 (48.2) and 93.9 (64.3) µg/L] and OxLDL [76.3 (52.3) and 82.2 (54.4) µg/L]. After adjustment for baseline variables patients on ATV/r had a significant decrease in Lp-PLA2 (estimated difference -16.3 [CI 95%: -31.4, -1.25; p=0.03]) and a significantly lower increase in OxLDL (estimated difference -21.8 [-38.0, -5.6; p<0.01] relative to those on EFV, whereas no differences in MPO were found. Adjusted changes in BR were significantly higher for the ATV/r group (estimated difference 1.33 [1.03, 1.52; p<0.01]). Changes in BR and changes in OS markers were significantly correlated. CONCLUSIONS In virologically suppressed patients on stable ART, OS was lower in ATV/r-based regimens compared to EFV. We hypothesize these changes could be in part attributable to increased BR plasma levels.

Trends in socioeconomic inequalities in preventable mortality in urban areas of 33 Spanish cities, 1996-2007 (MEDEA project).

Abstract Background: Preventable mortality is a good indicator of possible problems to be investigated in the primary prevention chain, making it also a useful tool with which to evaluate health policies particularly public health policies. This study describes inequalities in preventable avoidable mortality in relation to socioeconomic status in small urban areas of thirty three Spanish cities, and analyses their evolution over the course of the periods 1996–2001 and 2002–2007. Methods: We analysed census tracts and all deaths occurring in the population residing in these cities from 1996 to 2007 were taken into account. The causes included in the study were lung cancer, cirrhosis, AIDS/HIV, motor vehicle traffic accidents injuries, suicide and homicide. The census tracts were classified into three groups, according their socioeconomic level. To analyse inequalities in mortality risks between the highest and lowest socioeconomic levels and over different periods, for each city and separating by sex, Poisson regression were used. Results: Preventable avoidable mortality made a significant contribution to general mortality (around 7.5%, higher among men), having decreased over time in men (12.7 in 1996–2001 and 10.9 in 2002–2007), though not so clearly among women (3.3% in 1996–2001 and 2.9% in 2002–2007). It has been observed in men that the risks of death are higher in areas of greater deprivation, and that these excesses have not modified over time. The result in women is different and differences in mortality risks by socioeconomic level could not be established in many cities. Conclusions: Preventable mortality decreased between the 1996–2001 and 2002–2007 periods, more markedly in men than in women. There were socioeconomic inequalities in mortality in most cities analysed, associating a higher risk of death with higher levels of deprivation. Inequalities have remained over the two periods analysed. This study makes it possible to identify those areas where excess preventable mortality was associated with more deprived zones. It is in these deprived zones where actions to reduce and monitor health inequalities should be put into place. Primary healthcare may play an important role in this process. Keywords: Preventable avoidable mortality, Causes of death, Inequalities in health, Small area analysis

From diabetes to heart disease : studies on dyslipidemia-induced B-cell dysfunction, immunomodulation in heart transplantation, and cardiac stem cell therapy

Diabetes is a growing epidemic with devastating human, social and economic impact. It is associated with significant changes in plasma concentrations of lipoproteins. We tested the hypothesis that lipoproteins modulate the function and survival of insulin-secreting cells. We first detected the presence of several receptors that participate in the binding and processing of plasma lipoproteins and confirmed the internalization of fluorescent LDL and HDL particles in insulin-secreting β-cells. Purified human VLDL and LDL particles reduced insulin mRNA levels and β-cell proliferation, and induced a dose-dependent increase in the rate of apoptosis. In mice lacking the LDL receptor, islets showed a dramatic decrease in LDL uptake and were partially resistant to apoptosis caused by LDL. VLDL-induced apoptosis of β-cells involved caspase-3 cleavage and reduction in levels of the c-Jun N-terminal (JNK) Interacting Protein-1 (IB1/JIP-1). In contrast, the pro-apoptotic signaling of lipoproteins was antagonized by HDL particles or by a small peptide inhibitor of JNK. The protective effects of HDL were mediated, in part, by inhibition of caspase-3 cleavage and activation of the protein kinase Akt/PKB. Heart disease is a major cause of morbidity and mortality among patients with diabetes. When heart failure is refractory to medical therapy and cannot be improved by electrical resynchronization, percutaneous angioplasty or coronary graft bypass surgery, heart transplantation remains a "last resort" therapy. Nevertheless, it is limited by the side effects of immunosuppressive drugs and chronic rejection. Localized expression of immunomodulatory genes in the donor organ can create a state of immune privilege within the graft, and was performed in rodent hearts by infecting cells with an adenovirus encoding indoleamine 2,3-dioxygenase (IDO), the rate-limiting enzyme in the catabolism of tryptophane. Other strategies are based on genetic manipulation of dendritic cells (DCs) with immunosuppressive genes and in vitro exposure of DCs to agents that prevent their maturation by inflammatory cytokines. Finally, we used 5-bromo-2'-deoxyuridine, which is incorporated into DNA and diluted with cell division, to identify long-term label retaining cells in the adult rodent heart. The majority of these cells were positive for the stem cell antigen-1 (Sca-1) and negative for the endothelial precursor marker CD31. They formed cardiospheres in vitro and showed differentiation potential into mesenchymal cell lineages. When cultured in cardiomyogenic differentiation medium, they expressed cardiac-specific genes. Taken together, these data provide evidence of slow-cycling stem cells in the rodent heart. Chronic shortage of donor organs opens the way to cardiac stem cell therapy in humans, although the long way from animal experimentation to routine therapy in patients may still take several years. - Du diabète de type 2 à la maladie coronarienne : trois études sur les dysfonctions de la cellule sécrétrice d'insuline induites par les dyslipidémies, l'immunomodulation dans la transplantation cardiaque, et la thérapie par des cellules souches myocardiques. Le diabète de type 2 a pris les dimensions d'une épidémie, avec des conséquences sociales et économiques dont nous n'avons pas encore pris toute la mesure. La maladie s'accompagne souvent d'une dyslipidémie caractérisée par une hypertriglycéridémie, des taux abaissés de cholestérol HDL, et des concentrations de cholestérol LDL à la limite supérieure de ce qui est considéré comme acceptable. L'hypothèse à la base de cette étude est qu'une modification des taux plasmatiques de lipoprotéines pourrait avoir une influence directe sur la cellule β sécrétrice d'insuline en modifiant sa fonction, sa durée de vie et son taux de régénération. Dans un premier temps, nous avons mis en évidence, sur la cellule β, la présence de plusieurs récepteurs impliqués dans la captation des lipoprotéines. Nous avons confirmé la fonctionnalité de ces récepteurs en suivant l'internalisation de LDL et de HDL marqués. En présence de VLDL ou de LDL humains, nous avons observé une diminution de la transcription du gène de l'insuline, une prolifération cellulaire réduite, et une augmentation de l'apoptose, toutes fonctions de la dose et du temps d'exposition. L'apoptose induite par les VLDL passe par une activation de la caspase-3 et une réduction du taux de la protéine IB1/JIP-1 (Islet Brain1/JNK Interacting Protein 1), dont une mutation est associée à une forme monogénique de diabète de type 2. Par opposition, les HDL, ainsi que des peptides inhibiteurs de JNK, sont capables de contrer la cascade pro-apoptotique déclenchée, respectivement, par les LDL et les VLDL. Ces effets protecteurs comprennent l'inhibition du clivage de la caspase-3 et l'activation de la protéine kinase Akt/PKB. En conclusion, les lipoprotéines sont des éléments clés de la survie de la cellule β, et pourraient contribuer au dysfonctionnement observé dans le pancréas endocrine au cours du développement du diabète. La maladie cardiaque, et plus particulièrement la maladie coronarienne, est une cause majeure de morbidité et de mortalité chez les patients atteints de diabète. Plusieurs stratégies sont utilisées quotidiennement pour pallier les atteintes cardiaques: traitements médicamenteux, électromécaniques par resynchronisation électrique, ou communément appelés « interventionnels » lorsqu'ils font appel à l'angioplastie percutanée. La revascularisation du myocarde par des pontages coronariens donne également de très bons résultats dans certaines situations. Il existe toutefois des cas où plus aucune de ces approches n'est suffisante. La transplantation cardiaque est alors la thérapie de choix pour un nombre restreint de patients. La thérapie génique, en permettant l'expression locale de gènes immunomodulateurs dans l'organe greffé, permet de diminuer les réactions de rejet inhérentes à toute transplantation (à l'exception de celles réalisées entre deux jumeaux homozygotes). Nous avons appliqué chez des rongeurs cette stratégie en infectant le coeur greffé avec un adénovirus codant pour l'enzyme indoleamine 2,3-dioxygénase (IDO), une enzyme clé dans le catabolisme du tryptophane. Nous avons procédé de manière identique in vitro en surexprimant IDO dans les cellules dendritiques, dont le rôle est de présenter les antigènes aux lymphocytes Τ du receveur. Des expériences similaires ont été réalisées en traitant les cellules dendritiques avec des substances capables de prévenir, en partie du moins, leur maturation par des agents pro-inflammatoires. Finalement, nous avons exploré une stratégie utilisée couramment en hématologie, mais qui n'en est encore qu'à ses débuts au niveau cardiaque : la thérapie par des cellules souches. En traitant des rongeurs avec un marqueur qui s'incorpore dans l'ADN nucléaire, le 5-bromo- 2'-deoxyuridine, nous avons identifié une population cellulaire se divisant rarement, positive en grande partie pour l'antigène embryonnaire Sca-1 et négative pour le marqueur endothélial CD31. En culture, ces cellules forment des cardiosphères et sont capables de se différencier dans les principaux types tissulaires mésenchymateux. Dans un milieu de differentiation adéquat, ces cellules expriment des gènes cardiomyocytaires. En résumé, ces données confirment la présence chez le rongeur d'une population résidente de précurseurs myocardiques. En addenda, on trouvera deux publications relatives à la cellule β productrice d'insuline. Le premier article démontre le rôle essentiel joué par la complexine dans l'insulino-sécrétion, tandis que le second souligne l'importance de la protéine IB1/JIP-1 dans la protection contre l'apoptose de la cellule β induite par certaines cytokines.

Gender difference in the response to an angiotensin-converting enzyme inhibitor and a diuretic in hypertensive patients of African descent.

BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors in decreasing blood pressure in African patients is controversial. OBJECTIVE: We examined the ambulatory blood pressure (ABP) response to a diuretic and an ACE inhibitor in hypertensive patients of East African descent and evaluated the individual characteristics that determined treatment efficacy. DESIGN: A single-blind randomized AB/BA crossover design. SETTING: Hypertensive families of East African descent from the general population in the Seychelles. PARTICIPANTS: Fifty-two (29 men and 23 women) out of 62 eligible hypertensive patients were included.Main outcome measures ABP response to 20 mg lisinopril (LIS) daily and 25 mg hydrochlorothiazide (HCT) daily given for a 4-week period.Results The daytime systolic/diastolic ABP response to HCT was 4.9 [95% confidence interval (CI) 1.2-8.6]/3.6 (1.0-6.2) mmHg for men and 12.9 (9.2-16.6)/6.3 (3.7-8.8) mmHg for women. With LIS the response was 18.8 (15.0-22.5)/14.6 (12.0-17.1) mmHg for men and 12.4 (8.7-16.2)/7.7 (5.1-10.2) mmHg for women. The night-time systolic/diastolic response to HCT was 5.0 (0.6-9.4)/2.7 [(-0.4)-5.7] mmHg for men and 11.5 (7.1-16.0)/5.7 (2.6-8.8) mmHg for women, and to LIS was 18.7 (14.2-22.1)/15.4 (12.4-18.5) mmHg for men and 3.5 [(-1.0)-7.9]/2.3 [(-0.8)-5.4] mmHg for women. Linear regression analyses showed that gender is an independent predictor of the ABP responses to HCT and to LIS. CONCLUSIONS: Hypertensive patients of African descent responded better to LIS than to HCT. Men responded better to LIS than to HCT and women responded similarly to both drugs.

Whole-Body Vibration Training Elevates Creatine-Kinase Levels in Sedentary Subjects

METHODS: 20 inactive (10 male, 10 female) underwent a single typical WBV session, with a total of 27 minutes of exercise on an oscillating platform at 26 Hz, involving upper and lower body muscles. Each exercise lasted 90 seconds, with 40 seconds pauses inbetween. Muscle enzymes (CK, transaminase, LDH, troponin I) were measured before, at 24, 48 and 96 hours post exercise. Lactate was measured immediately after the session. Muscle aches were assessed during 4 days post-exercise.RESULTS: Subjects' mean age was 23.0 ± 3.5 (male), 22.4 ± 1.4 (female), BMI 22.8 ± 2.3 and 22.1 ± 1.9, and all had been inactive for at least 12 months. Post exercise lactatemia was 10.0 ± 2.4 and 6.9 ± 2.4. CK elevation was significant (at least doubling of baseline values) in 1 male and 4 female subjects, while they remained at baseline values for the remaining 15 subjects. One female subject peaked at 3520 U/l at 96 hours post exercise, and all but one peaked at the same late time. Troponin and CK-MB never increased. No correlation was found between muscle soreness and CK levels.CONCLUSIONS: WBV can elicit important anaerobic processes reflected by the high lactacidemia, and CK elevation was significant in 25 % of subjects, peaking at the fourth day after exercise for 80 % of those. Such exercises should not be regarded as trivial and "easy" as they are advertised, since they can provoke important anaerobia and CK elevation. Many fragile patients or patients treated for cardiovascular disease could benefit from WBV but it is important to recognise these potential effects, especially in those treated with statins, known to cause a myopathy and CK elevation. Before considering a side effect of an important therapeutic agent, doctors should be aware of the possible interaction with not-so-harmless exercising machines.

Decision-support tools to manage drug incompatibilities: evaluation by nurses

Introduction Preventing drug incompatibilities has a high impact onthe safety of drug therapy. Although there are no internationalguidelines to manage drug incompatibilities, different decision-supporttools such as handbooks, cross-tables and databases are available.In a previous study, two decision-support tools have been pre-selectedby pharmacists as fitting nurses' needs on the wards1. The objective ofthis study was to have these both tools evaluated by nurses todetermine which would be the most suitable for their daily practice.Materials & Methods Evaluated tools were:1. Cross-table of drug pairs (http://files.chuv.ch/internet-docs/pha/medicaments/pha_phatab_compatibilitessip.pdf)2. Colour-table (a colour for each drug according to the pH: red =acid; blue = basic; yellow = neutral; black = to be infused alone)2Tools were assessed by 48 nurses in 5 units (PICU, adult andgeriatric intensive care, surgery, onco-hematology) using a standardizedform1. The scientific accuracy of the tools was evaluated bydetermining the compatibility of five drugs pairs (rate of correctanswers according to the Trissel's Handbook on Injectable Drugs,chi-square test). Their ergonomics, design, reliability and applicabilitywere estimated using visual analogue scales (VAS 0-10; 0 =null, 10 = excellent). Results are expressed as the median and interquartilerange (IQR) for 25% and 75% (Wilcoxon rank sum test).Results The rate of correct answers was above 90% for both tools(cross-table 96.2% vs colour-table 92.5%, p[0.05).The ergonomics and the applicability were higher for the crosstable[7.1 (IQR25 4.0, IQR75 8.0) vs 5.0 (IQR25 2.7, IQR75 7.0), p =0.025 resp. 8.3 (IQR25 7.4, IQR75 9.2) vs 7.6 (IQR25 5.9, IQR75 8.8)p = 0.047].The design of the colour-table was judged better [4.6 (IQR25 2.9,IQR75 7.1) vs 7.1 (IQR25 5.4, IQR75 8.4) p = 0.002].No difference was observed in terms of reliability [7.3 (IQR25 6.5,IQR75 8.4) vs 6.7 (IQR25 5.0, IQR758.6) p[0.05].The cross-table was globally preferred by 65% of the nurses (27%colour-table, 8% undetermined) and 68% would like to have thisdecision-support tool available for their daily practice.Discussion & Conclusion Both tools showed the same accuracy toassess drug compatibility. In terms of ergonomics and applicabilitythe cross-table was better than the colour-table, and was preferred bythe nurses for their daily practice. The cross-table will be implementedin our hospital as decision-support tool to help nurses tomanage drug incompatibilities.

Análise de causa raiz: avaliação de erros de medicação em um hospital universitário

Os objetivos deste estudo foram identificar e analisar os tipos de erros de medicação observados nas doses de medicamentos que foram preparadas e administradas de forma diferente daquelas prescritas. Estudo descritivo, utilizando o método de análise de causa raiz, que realizou uma análise secundária de dados de um estudo já existente. No estudo, 74 erros de medicação foram identificados, durante o preparo e a administração de medicamentos pela equipe de enfermagem. Erros de dose (24,3%), erros de horário (22,9%) e medicamentos não autorizados (13,5%) foram os mais frequentes. Assim, a análise de causa raiz foi realizada, identificando múltiplos fatores que contribuíram para a ocorrência dos erros, e estratégias e recomendações foram apresentadas para evitá-los.

Hipertensos com e sem doença renal: avaliação de fatores de risco

RESUMO Objetivo Comparar pacientes hipertensos com e sem doença renal e identificar fatores associados à condição clínica e tratamento anti-hipertensivo. Método Estudo transversal realizado com pacientes admitidos em clínica médica de um hospital universitário da cidade de São Paulo. Os dados foram coletados por meio de análise do prontuário. Valores de p<0,05 foram considerados significantes. Resultados Dos 386 pacientes avaliados, 59,3% eram hipertensos e destes 37,5% tinham doença renal crônica. Houve associação independente da presença de doença renal crônica para antecedentes de diabetes (OR 1,86; IC 1,02-3,41) e de insuficiência cardíaca congestiva (OR 3,42; IC 1,36-9,03); além do fato de viver com companheiro (OR 1,99; IC 1,09-3,69). Quanto ao tratamento anti-hipertensivo, houve diferença (p<0,05) entre os hipertensos com e sem doença renal em relação a fazer acompanhamento de saúde (93,2%vs 77,7%); uso contínuo de medicamentos anti-hipertensivos, (79,1% vs 66,4%); maior número de medicamentos anti-hipertensivos; uso de bloqueadores beta-adrenérgicos (34,9% vs 19,6%), bloqueadores dos canais de cálcio (29,1%vs 11,2%), diuréticos de alça (30,2%vs 10,5%) e vasodilatadores (9,3% vs2,1%). Conclusão Os hipertensos com doença renal crônica apresentaram perfil clínico mais comprometido, porém em relação ao tratamento anti-hipertensivo as atitudes foram mais positivas do que os sem doença renal.

Evaluation de l'efficacite antihypertensive de l'isradipine SRO par enregistrement tensionnel en ambulatoire. [Evaluation of the antihypertensive efficacy of isradipine SRO as assessed by ambulatory blood pressure determination]

The calcium channel blocker isradipine has become recently available in a form with delayed release (isradipine SRO). The anti-hypertensive efficacy and tolerance of this preparation at a single daily dose of 5 mg was studied in 40 patients with uncomplicated essential hypertension over a period of 6 weeks. Blood pressure during office visits decreased under Isradipine SRO from 164/105 +/- 16/7 to 144/93 +/- 12/7 mmHg (mean +/- 1 standard deviation p < 0.001). Using ambulatory blood pressure recording we could show that antihypertensive efficacy of the new galenic form persisted over 24 hours. During the day the blood pressure dropped from 150/95 +/- 13/7 to 141/91 +/- 13/7 mmHg (p < 0.001), during the night from 131/85 +/- 13/3 to 121/81 +/- 15/9 mmHg (p < 0.001). Heart-rate was not changed by treatment and the drug was well tolerated. Isradipine SRO at a single dose is thus well suited for antihypertensive treatment.

Consumption of Cinara spp. (Hemiptera, Aphididae) by Cycloneda sanguinea (Linnaeus, 1763) and Hippodamia convergens Guérin-Méneville, 1842 (Coleoptera, Coccinellidae)

Adults and larvae of coccinellids were observed feeding on populations of the giant conifer aphids Cinara spp. on Pinus spp., in Southern Brazil. The objective of this research is to evaluate the consumption capacity of Cycloneda sanguinea (Linnaeus, 1763) and Hippodamia convergens Guérin-Méneville, 1842 (Coleoptera, Coccinellidae) on these aphid species, in order to obtain information for biological control programs. Ten larvae of each predator species were fed with aphids of small size (nymphs of 1st and 2nd instars), and 10 with aphids of medium size (nymphs of 3rd and 4th instars), maintained under 15ºC, 20ºC and 25ºC, 12 h photophase and 70 ± 10% relative humidity. The aphids were counted every 24 hours, replacing those that were consumed. The total consumption of Cinara by the larvae of C. sanguinea was not statistically different at the three temperatures: 325.5; 322.2 and 324.8 of small aphids and 121.3; 140.4 and 109.9 of medium ones, respectively at 15ºC, 20ºC and 25ºC. The consumption by H. convergens was higher than by C. sanguinea and increased noticeably with temperature: 444 aphids at 15ºC; 491.3 at 20ºC and 513.3 at 25ºC, considering the small aphids, and 187.1; 205.1 and 216.6 of medium aphids at the three temperatures. The small aphids weigh about half as much as medium ones and were preferred by all larval instars probably because they are easier to manipulate than the large ones. Both predators, especially the 4th instar larvae, showed high consumption capacity on the Cinara nymphs at all temperatures and can be regarded as promising biological control agents.

Natural parasitism in eggs of Anticarsia gemmatalis Hübner (Lepidoptera, Noctuidae) by Trichogramma spp. (Hymenoptera, Trichogrammatidae) in Brazil

Field surveys were carried during four soybean seasons in Southern Brazil to evaluate the occurrence of parasitoids in eggs of Anticarsia gemmatalis Hübner, 1818 and their incidence along the crop season. Eggs were collected by visual search on soybean leaves and from plants kept inside cages where A. gemmatalis moths were allowed to lay eggs. Trichogramma acacioi Brun, Moraes & Soares, 1984 was recorded for the first time in eggs of A. gemmatalis and the citations in the literature of Trichogramma lasallei Pinto, 1998 in Brazil where based on the material collected in this survey. Apart from these species, Trichogramma pretiosum Riley, 1879, Trichogramma rojasi Nagaraja & Nagarkatti, 1973 and Trichogramma atopovirilia Oatman & Platner, 1983 were also collected, all of which have been previously recorded in this host. Parasitized eggs were collected all over the period of occurrence of A. gemmatalis, from January to April each year. Total parasitism ranged from 4.8% in 2000 and 2002, 23.3% in 2001 and 28.9% in 2003. T. pretiosum and T. acacioi accounted for more than 80% of the parasitoids emerged each year, followed by T. atopovirilia, T. rojasi and T. lasallei, with less than 20% of incidence. Both the sex ratio and the mean number of parasitoids/egg did not differ among the species. Searching for A. gemmatalis eggs proved to be time consuming in comparison to the collection of eggs laid by moths inside the cages, which showed to be a useful method to provide qualitative estimates of parasitism in eggs of A. gemmatalis.

Percutaneous central venous catheterization in premature infants: a method for facilitating insertion of silastic catheters via peripheral veins.

Peripheral venous cannulation is the preferred method of inserting central venous silastic catheters in premature infants. The standard techniques are placement of the catheter using a breakaway introducer needle or introduction of the catheter through a cannula. In extremely low birth weight infants (<1000 g) successful cannulation is impeded by the small size of the vessels. After repeated attempts, both procedures can be time-consuming and stressful to the infant. We present a modified insertion technique of the standard 2-French silastic catheter with an increased success rate, thus reducing insertion time, stress to the infant, and costs. The method uses the tip of a 20-gauge cannula as dilator/introducer for the 2-French catheter. This tip is inserted into the vessel with a standard 24-gauge cannula. After successful insertion of the dilator/introducer cannula, the standard 2-French catheter can then be advanced easily.

HACEK infective endocarditis: characteristics and outcomes from a large, multi-national cohort.

The HACEK organisms (Haemophilus species, Aggregatibacter species, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) are rare causes of infective endocarditis (IE). The objective of this study is to describe the clinical characteristics and outcomes of patients with HACEK endocarditis (HE) in a large multi-national cohort. Patients hospitalized with definite or possible infective endocarditis by the International Collaboration on Endocarditis Prospective Cohort Study in 64 hospitals from 28 countries were included and characteristics of HE patients compared with IE due to other pathogens. Of 5591 patients enrolled, 77 (1.4%) had HE. HE was associated with a younger age (47 vs. 61 years; p<0.001), a higher prevalence of immunologic/vascular manifestations (32% vs. 20%; p<0.008) and stroke (25% vs. 17% p = 0.05) but a lower prevalence of congestive heart failure (15% vs. 30%; p = 0.004), death in-hospital (4% vs. 18%; p = 0.001) or after 1 year follow-up (6% vs. 20%; p = 0.01) than IE due to other pathogens (n = 5514). On multivariable analysis, stroke was associated with mitral valve vegetations (OR 3.60; CI 1.34-9.65; p<0.01) and younger age (OR 0.62; CI 0.49-0.90; p<0.01). The overall outcome of HE was excellent with the in-hospital mortality (4%) significantly better than for non-HE (18%; p<0.001). Prosthetic valve endocarditis was more common in HE (35%) than non-HE (24%). The outcome of prosthetic valve and native valve HE was excellent whether treated medically or with surgery. Current treatment is very successful for the management of both native valve prosthetic valve HE but further studies are needed to determine why HE has a predilection for younger people and to cause stroke. The small number of patients and observational design limit inferences on treatment strategies. Self selection of study sites limits epidemiological inferences.