Sepse tardia em Unidade de Tratamento Intensivo Neonatal / Late-onset sepsis in a Neonatal Intensive Care Unit / Sepse tardía en Unidad de Tratamiento Intensivo Neonatal

Justificativa e Objetivos: É essencial conhecer os microrganismos presentes em hemoculturas de pacientes pediátricos internados para uma melhor escolha da terapêutica antibiótica. Dessa forma, este trabalho tem como objetivo verificar a associação entre parâmetros clínicos e epidemiológicos com o desenvolvimento de sepse neonatal tardia em pacientes internados em um serviço de pediatria de um hospital do sul do Brasil. Métodos: Estudo transversal, descritivo, retrospectivo e qualiquantitativo que utilizou dados secundários oriundos dos prontuários de pacientes que apresentaram critérios clínicos para sepse neonatal, internados na Unidade de Tratamento Intensivo Neonatal (UTIN) do Hospital Santa Cruz. Resultados: Dos 588 pacientes internados na UTIN do Hospital Santa Cruz no período de 01/01/2013 a 31/12/2015, 123 recém-nascidos (RNs) preencheram os critérios para sepse neonatal tardia. Destes, 59 (47,97%) apresentaram hemocultura positiva, o que foi mais frequente em RNs prematuros (39,84%) e de baixo peso (43,90%), embora não tenha havido associação estatisticamente significativa entre estes fatores e hemocultura positiva. Dentre os possíveis fatores de risco para o desenvolvimento de sepse neonatal, o uso de ventilação mecânica (p=0,005), realização de cirurgia (p=0,019) e permanência no hospital por mais de um mês (p=0,001) apresentaram associação estatística com hemocultura positiva. Os microrganismos presentes em maior frequência nas hemoculturas foram os estafilococos coagulase-negativa (S. epidermidis, S. saprophyticus e S. haemolyticus), encontrados em 35,71% das hemoculturas analisadas. Conclusão: O estudo evidenciou maior prevalência de sepse neonatal tardia em RNs prematuros e de baixo peso, que necessitaram de maiores cuidados e foram submetidos a maior manipulação durante a permanência na UTIN. Procedimentos invasivos e longa permanência hospitalar se associaram significativamente com hemocultura positiva, corroborando com o descrito na literatura.(AU)

Background and Objectives: It is essential recognize the microorganisms present in hemoculture in pediatric patients internees for a better choice of antibiotic therapy. In this way, this work aims assess the association between clinical and epidemiological parameters with the onset of late neonatal sepsis in hospitalized patients, in a pediatric service of the south of Brazil. Methods: A cross-sectional, descriptive, retrospective, qualitative and quantitative study that used secondary data from the files of patients which presented clinical criteria indicating neonatal sepsis, that were hospitalized in the Neonatal Intensive Care Unit (NICU) at Hospital Santa Cruz. Results: Out of the 588 patients hospitalized in the NICU from 01/01/2013 to 12/31/2015, 123 newborns (NBs) filled the criteria for late neonatal sepsis. Out of these, 59 (47,97%) presented with positive hemoculture, which was more frequent in preterms NBs (39,84%) and low birth weight (43,90%), although there was no statistically significant associantion between these factors and positive hemoculture. From the possible risk factors for the onset of neonatal sepsis, mechanical ventilation (p=0,005), having performed surgery (p=0,019) and in-hospital stay longer than a month (p=0,001) showed statistic association with positive hemoculture. The microrganisms that were the most frequent were the coagulase-negative staphylococci (S. epidermidis, S. saprophyticu and S. haemolyticus), found in 37,71% of the analyzed hemocultures. Conclusion: This study showed higher prevalence of neonatal sepsis on premature NBs and on low-weight NBs that required higher care and suffered invasive procedures during the stay in the NICU. Invasive procedures and long hospital stay were significantly associated with positive hemoculture, corroborating with tah described in the literature.(AU)

Justificación y objetivos: Es esencial conocer los microorganismos presentes em las hemoculturas de pacientes pediátricos internados para una mejor elección de la terapia antibiótica. De esta forma, este trabajo tiene como objetivo verificar la asociación entre parámetros clínicos y epidemiológicos con el desarrollo de sepsis neonatal tardía en pacientes internados en un servicio de pediatría de un hospital del sur de Brasil. Métodos: Estudio transversal, descriptivo, retrospectivo y cualiquantitativo que utilizó datos secundarios oriundos de los prontuarios de pacientes que presentaron criterios clínicos para sepsis neonatal, internados en la Unidad de Tratamiento Intensivo Neonatal (UTIN) del Hospital Santa Cruz. Resultados: De los 588 pacientes internados en la UTIN del Hospital Santa Cruz en el período de 01/01/2013 a 31/12/2015, 123 recién nacidos (RNs) cumplieron los criterios para sepsis neonatal tardía. De estos, 59 (47,97%) presentaron hemocultura positiva, lo que fue más frecuente en RNs prematuros (39,84%) y de bajo peso (43,90%), aunque no hubo asociación estadísticamente significativa entre estos factores y hemocultura positiva. Entre los posibles factores de riesgo para el desarrollo de sepsis neonatal, el uso de ventilación mecánica (p=0,005), realización de cirugía (p=0,019) y permanencia en el hospital por más de un mês (p=0,001) presentaron asociación estadística con hemocultura positiva. Los microorganismos presentes en mayor frecuencia en los hemocultivos fueron los estafilococos coagulasa-negativos (S. epidermidis, S. saprophyticus y S. haemolyticus), encontrados en el 35,71% de los hemocultivos analizados. Conclusión: El estudio evidenció mayor prevalencia de sepsis neonatal tardía en RNs prematuros y de bajo peso, que requirieron mayores cuidados y fueron sometidos a mayor manipulación durante la permanencia en la UTIN. Los procedimientos invasivos y larga permanencia hospitalaria se asociaron significativamente con hemocultura positiva, corroborando con lo descrito en la literatura.(AU)

IOEASMA: an integrated clinical and educational pathway for managing asthma in children and adolescents.

BACKGROUND: Due to the lack of real life clinical and educational studies, "Io e l'Asma" Centre performed this implementation research (IR). Evaluate long-term effectiveness on bronchial asthma control of an integrated clinical and educational pathway for asthmatic children and adolescents. METHODS: An observational retrospective pre-post intervention IR study was conducted among 262 children with asthma, ages 6-15 yrs. The intervention protocol included three clinical visits 8 weeks apart; an educational course at visit 1, post intervention consisted in two follow-up visits 6 months apart. The primary outcome was to verify the percentage of children who achieved bronchial asthma control at each visit. Secondary outcomes were based on daily therapy modulation, hospital admissions and the number of school days missed. An economic assessment was also included. RESULTS: Two hundred sixty two children with bronchial asthma completed the pathway and were included in the analysis. The percentage of children who obtained disease control increased from 44% at visit 1 to 79% at visit 3 and at 1-year follow-up was 83%. Hospital admissions represent 11% of children: 8% before the intervention, 2% during the intervention, and 1% before and during the intervention; no hospitalizations related to bronchial asthma exacerbations were reported during the 2 follow-up visits. CONCLUSIONS: The therapeutic-educational pathway was adapted according to the international guidelines and the primary performance indicators. Our findings confirmed that the clinical plus educational approach, shared between specialists and family physicians, is an effective template for asthma management. These findings also demonstrated a strong economic advantage.

Histopathological differences between genders in patients with oral squamous cell carcinoma

Introduction: Oral cancer ranks fifth among the most frequent malignant tumors in men in Brazil. The incidence of this tumor among women has grown. It is still controversial whether gender can influence the outcome or the prognostic features of the disease. Objectives: To compare the histopathological features of oral squamous cell carcinomas between genders among patients undergoing surgical treatment in an oncological hospital of southern Brazil. Methods: Between 2007 and 2011, 404 patients underwent resection of malignant tumors of the oral cavity in the head and neck department of this institution. A subgroup of 209 previously untreated oral cavity squamous cell carcinoma cases was selected for comparative analysis. Results: In total, 68 participants were women and 141 were men. The tongue was the most common subsite in both genders. Men presented lower mean age and women presented tumors with smaller depth of invasion. Although among women it was observed a trend towards tumors with less aggressive characteristics, no other variable showed statistically significance. Conclusion: Women with oral tumors tend to present more superficial primary tumors and at a later age (AU)

Serological screening for celiac disease in a northern Italian child and adolescent population after the onset of type 1 diabetes: a retrospective longitudinal study of a 7-year period.

AIM: To evaluate the temporal trend and extent of screening for celiac disease in an Italian pediatric population of incident type 1 diabetes in the period 2006-2011, providing information on adherence to guidelines in primary care. METHODS: Using the Lombardy region's administrative database, 1-17-year-old children and adolescents diagnosed with type 1 diabetes during the 2006-2011 period were identified. Among these patients, the number screened for celiac disease was calculated on the basis of specific antibodies. RESULTS: Of the 1563 children and adolescents receiving a diagnosis of type 1 diabetes during the observational period, 53% were tested for celiac disease compared with 12% of individuals without diabetes. The extent to which screening was performed increased two-fold from the 2006-2008 to the 2009-2011 period (P<0.0001). Among the screened population, 1.8 of the non-type 1 diabetes population and 9.4% of the new cases of type 1 diabetes received a diagnosis of celiac disease (90% after type1 diabetes diagnosis and 10% before). Being female and less than 4 years old were factors associated with an increased risk of receiving both diagnoses. CONCLUSION: In conclusion, to the best of our knowledge, this is the first report in which celiac disease screening is measured in a type 1 diabetes population from the time of diagnosis up to at least 12 months afterwards. The results provide evidence that, although the rate of screening increased over time, nearly half of children with type 1 diabetes were not screened after diagnosis during the observed period, suggesting scarce adherence to guidelines in primary care.

Childhood asthma management pre- and post-incident asthma hospitalization.

Many hospitalizations for asthma could potentially be avoided with appropriate management. The aim of this study was to analyze data on disease management of a paediatric population with a hospitalization for asthma. The study population comprised 6-17 year old subjects belonging to three local health units of the Lombardy Region, northern Italy. Regional administrative databases were used to collect data on: the number of children with an incident hospitalization for asthma during the 2004-2006 period, anti-asthma therapy, specialist visit referrals, and claims for spirometry, released in the 12 months before and after hospitalization. Each patient's asthma management profile was compared with GINA guideline recommendations. Among the 183 hospitalized subjects, 101 (55%) received therapy before hospitalization and 82 (45%) did not. 10% did not receive any therapy either before or after hospital admission and in 13% the therapy was discontinued afterward. Based on GINA guidelines, asthma management adhered to recommendations only for 55% of subjects. Results may suggest that for half of hospitalized subjects, inaccurate diagnosis, under-treatment/scarce compliance with asthma guidelines by physicians, and/or scarce compliance to therapy by patients/their parents occurred. In all these cases, hospitalization would be a proxy indicator of preventable poor control of disease, rather than a proxy indicator of severity.

Spirometry testing in a population of Italian children: age and gender differences.

AIM: To estimate how many asthmatic children underwent spirometry testing in one year in a large Italian region, and evaluate sociodemographic determinants. METHODS: Data were retrieved from the administrative databases that store all pharmacological and diagnostic prescriptions issued to individuals living in the Lombardy Region. The analysis involved prescriptions dispensed to all 6-17 year olds (1,047,241 subjects) during 2008. Youths were identified as asthmatics by a previously validated strategy. Number of subjects having ≥1 spirometry claims was calculated, and factors associated with the probability of undergoing spirometry were evaluated by multivariate analysis. RESULTS: A total of 40,528 (3.9%) asthmatic subjects were identified. Only 30% of them underwent ≥1 spirometry during 2008, with differences between local health units (range 22-45%) and degree of anti-asthmatic use (26-35%). Moreover, in a multivariate analysis, the chance of undergoing spirometry was greater in boys than in girls (OR=2.3). CONCLUSIONS: A low percentage of asthmatic children, especially girls (who are more at risk of developing severe disease in adulthood), underwent spirometry during 1-year period. This highlights a low compliance with guidelines in the monitoring of childhood asthma. Educational intervention is needed in order to encourage use of spirometry in primary care settings.

Long-term outcomes of patients with cerebral vein thrombosis: a multicenter study.

BACKGROUND: Little information is available on the long-term clinical outcome of cerebral vein thrombosis (CVT). OBJECTIVES AND METHODS: In an international, retrospective cohort study, we assessed the long-term rates of mortality, residual disability and recurrent venous thromboembolism (VTE) in a cohort of patients with a first CVT episode. RESULTS: Seven hundred and six patients (73.7% females) with CVT were included. Patients were followed for a total of 3171 patient-years. Median follow-up was 40 months (range 6, 297 months). At the end of follow-up, 20 patients had died (2.8%). The outcome was generally good: 89.1% of patients had a complete recovery (modified Rankin Score [mRS] 0-1) and 3.8% had a partial recovery and were independent (mRS 2). Eighty-four per cent of patients were treated with oral anticoagulants and the mean treatment duration was 12 months. CVT recurred in 31 patients (4.4%), and 46 patients (6.5%) had a VTE in a different site, for an overall incidence of recurrence of 23.6 events per 1000 patient-years (95% confidence Interval [CI] 17.8, 28.7) and of 35.1 events/1000 patient-years (95% CI, 27.7, 44.4) after anticoagulant therapy withdrawal. A previous VTE was the only significant predictor of recurrence at multivariate analysis (hazard ratio [HR] 2.70; 95% CI 1.25, 5.83). CONCLUSIONS: The long-term risk of mortality and recurrent VTE appears to be low in patients who survived the acute phase of CVT. A previous VTE history independently predicts recurrent events.

Aspirin for preventing the recurrence of venous thromboembolism.

BACKGROUND: About 20% of patients with unprovoked venous thromboembolism have a recurrence within 2 years after the withdrawal of oral anticoagulant therapy. Extending anticoagulation prevents recurrences but is associated with increased bleeding. The benefit of aspirin for the prevention of recurrent venous thromboembolism is unknown. METHODS: In this multicenter, investigator-initiated, double-blind study, patients with first-ever unprovoked venous thromboembolism who had completed 6 to 18 months of oral anticoagulant treatment were randomly assigned to aspirin, 100 mg daily, or placebo for 2 years, with the option of extending the study treatment. The primary efficacy outcome was recurrence of venous thromboembolism, and major bleeding was the primary safety outcome. RESULTS: Venous thromboembolism recurred in 28 of the 205 patients who received aspirin and in 43 of the 197 patients who received placebo (6.6% vs. 11.2% per year; hazard ratio, 0.58; 95% confidence interval [CI], 0.36 to 0.93) (median study period, 24.6 months). During a median treatment period of 23.9 months, 23 patients taking aspirin and 39 taking placebo had a recurrence (5.9% vs. 11.0% per year; hazard ratio, 0.55; 95% CI, 0.33 to 0.92). One patient in each treatment group had a major bleeding episode. Adverse events were similar in the two groups. CONCLUSIONS: Aspirin reduced the risk of recurrence when given to patients with unprovoked venous thromboembolism who had discontinued anticoagulant treatment, with no apparent increase in the risk of major bleeding. (Funded by the University of Perugia and others; WARFASA ClinicalTrials.gov number, NCT00222677.).

Anti-asthma medication prescribing to children in the Lombardy Region of Italy: chronic versus new users.

BACKGROUND: Although anti-asthma medications are amongst those most frequently under or over prescribed it is generally accepted that prescriptions for such agents can be used as a proxy for disease prevalence. The aims of this study were to estimate prevalence and incidence of childhood asthma in a representative Italian area by analysing three years of anti-asthmatic prescriptions and hospitalizations of subjects with chronic or first time treatment, and to underline appropriateness of therapeutic choices. METHODS: The analysis involved prescriptions given to 6-17 year olds between 2003 and 2005 in Italy's Lombardy Region. The youths were classified as potential asthmatics, based on the different degree of drug utilization: occasional, low or high users, and grouped as 'new onset' or 'chronic' cases based on the duration of therapy dispensed. The analysis of prescriptions and hospitalization rate of these groups provided an estimate of the 2005 asthma prevalence and incidence and allowed an estimation of the level of appropriateness of treatments. RESULTS: During 2005, the estimated incidence of potential asthmatics was 0.8% and the estimated prevalence was 3.5%. When viewed retrospectively for two years, records showed that 47% of potential asthmatics received prescriptions also during 2004 and 30% also during 2003. During the three years considered, 7.5%, 2.8%, and 1.5% of high, low, and occasional users, respectively, were hospitalized for asthma. The most important inappropriateness found was the prescription of long acting beta adrenergics as first time treatment. CONCLUSIONS: This study allowed a proxy of asthma incidence, prevalence, and severity. The analyses highlighted a low compliance with the guidelines, suggesting that educational interventions are needed to obtain a more rational management of childhood asthma, especially in subjects starting therapy.

Multidetector computed tomography for acute pulmonary embolism: diagnosis and risk stratification in a single test.

AIMS: In patients with acute pulmonary embolism (PE), right ventricular dysfunction at echocardiography is associated with increased in-hospital mortality. The aims of this study in patients with acute PE were to identify a sensitive and simple criterion for right ventricular dysfunction at multidetector computed tomography (MDCT) using echocardiography as the reference standard and to evaluate the predictive value of the identified MDCT criterion for in-hospital death or clinical deterioration. METHODS AND RESULTS: Right ventricular dysfunction at MDCT was defined as the right-to-left ventricular dimensional ratio and was centrally assessed by a panel unaware of clinical and echocardiographic data. A right-to-left ventricular dimensional ratio ≥0.9 at MDCT had a 92% sensitivity for right ventricular dysfunction [95% confidence interval (CI) 88-96]. Overall, 457 patients were included in the outcome study: 303 had right ventricular dysfunction at MDCT. In-hospital death or clinical deterioration occurred in 44 patients with and in 8 patients without right ventricular dysfunction at MDCT (14.5 vs. 5.2%; P< 0.004). The negative predictive value of right ventricular dysfunction for death due to PE was 100% (95% CI 98-100). Right ventricular dysfunction at MDCT was an independent predictor for in-hospital death or clinical deterioration in the overall population [hazard ratio (HR) 3.5, 95% CI 1.6-7.7; P= 0.002] and in haemodynamically stable patients (HR 3.8, 95% CI 1.3-10.9; P= 0.007). CONCLUSION: In patients with acute PE, MDCT might be used as a single procedure for diagnosis and risk stratification. Patients without right ventricular dysfunction at MDCT have a low risk of in-hospital adverse outcome.

Emergency reversal of anticoagulation with a three-factor prothrombin complex concentrate in patients with intracranial haemorrhage.

BACKGROUND: Intracranial haemorrhage is a serious and potentially fatal complication of oral anticoagulant therapy. Prothrombin complex concentrates can substantially shorten the time needed to reverse the effects of oral anticoagulants. The aim of this study was to determine the efficacy and safety of a prothrombin complex concentrate for rapid reversal of oral anticoagulant therapy in patients with intracranial haemorrhage. METHODS: Patients receiving oral anticoagulant therapy and suffering from acute intracranial haemorrhage were eligible for this prospective cohort study if their International Normalised Ratio (INR) was higher than or equal to 2.0. The prothrombin complex concentrate was infused at doses of 35-50 IU/kg, stratified according to the initial INR. RESULTS: Forty-six patients (25 males; mean age: 75 years; range 38-92 years) were enrolled. The median INR at presentation was 3.5 (range, 2-9). At 30 minutes after administration of the prothrombin complex concentrate, the median INR was 1.3 (range, 0.9-3), and the INR then declined to less than or equal to 1.5 in 75% of patients. The benefit of the prothrombin complex concentrate was maintained for a long time, since the median INR remained lower than or equal to 1.5 (median, 1.16; range, 0.9-2.2) at 96% of all post-infusion time-points up to 96 hours. No thrombotic complications or significant adverse events were observed during hospitalisation; six patients (13%) died, but none of these deaths was judged to be related to administration of the prothrombin complex concentrate. CONCLUSIONS: Prothrombin complex concentrates are an effective, rapid and safe treatment for the urgent reversal of oral anticoagulation in patients with intracranial haemorrhage. Broader use of prothrombin complex concentrates in this clinical setting appears to be appropriate.

Inter-country variations in anti-asthmatic drug prescriptions for children. Systematic review of studies published during the 2000-2009 period.

OBJECTIVE: The objective of this study was to analyse inter-and intra-country quantitative and qualitative differences in anti-asthmatic prescriptions to children and adolescents. METHODS: A literature search was performed in EMBASE and MEDLINE to identify pharmaco-epidemiological studies published from January 1, 2000 to December 31, 2008 in which anti-asthmatic prescription prevalence in out-hospital children was measured. A meta-analytic weighted average and 95% confidence intervals of prescription prevalences were calculated using a random-effect(s) model. Inter- and intra-country quantitative and, where possible, qualitative prescribing patterns were compared and assessed. RESULTS: Twelve studies were identified (ten from Europe, one from Canada and one from the USA), but epidemiological indicators varied widely, and only eight were suitable for meta-analysis. The data from these studies revealed inter-country quantitative differences in prescription prevalences in the overall population

Anti-asthmatic drug prescriptions to an Italian paedriatic population.

To estimate the prevalence and evaluate the appropriateness of anti-asthmatic drug prescriptions in an Italian paediatric population, drug prescriptions involving 24,407 children <18 years old, dispensed during 2003 by the retail pharmacies of the local health unit in Lecco, Italy, were analysed. Children > or = 6 years old receiving anti-asthmatics were categorized into three subgroups based on the number of boxes prescribed: occasional (one box), low (two and three boxes) and high (> or = four boxes) users. A logistic regression analysis was performed to estimate the relationship between the drug use patterns and formulations, antibiotic co-prescriptions, systemic steroid prescriptions and rate of hospitalization. Anti-asthmatic drugs were prescribed to 6594 (12%) children and adolescents; 58% of whom received only one box of the drug. Prevalence varied according to age, with the highest values at 1 and 4 years (24% and 21% respectively), and decreased to 6% in 17-year-old adolescents. Inhaled steroids were the most prescribed drugs (83%). The most common of these was beclomethasone. Occasional, low and high users represented 58%, 29%, and 13%, respectively, of the treated population > or = 6 years old. High users were found to be at increased risk of systemic steroid prescriptions (OR 8.6) and hospital admission for asthma (OR 6.8). This study confirms that in Italy the prevalence of anti-asthmatic prescription is much higher than prevalence of disease, indicating that anti-asthmatics are over-prescribed. Moreover, steroids, especially nebulized, are mainly prescribed only once in a year, supporting the idea that are prescribed not for asthma, which as chronic disease requires a chronic therapy. The approach to create subgroups on the basis of number of boxes prescribed seems to be effective in estimating asthma severity and appropriateness of the therapies.

Inhibition of microglial inflammation by the MLK inhibitor CEP-1347.

CEP-1347 is a potent inhibitor of the mixed lineage kinases (MLKs), a distinct family of mitogen-activated protein kinase kinase kinases (MAPKKK). It blocks the activation of the c-Jun/JNK apoptotic pathway in neurons exposed to various stressors and attenuates neurodegeneration in animal models of Parkinson's disease (PD). Microglial activation may involve kinase pathways controlled by MLKs and might contribute to the pathology of neurodegenerative diseases. Therefore, the possibility that CEP-1347 modulates the microglial inflammatory response [tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1)] was explored. Indeed, the MLK inhibitor CEP-1347 reduced cytokine production in primary cultures of human and murine microglia, and in monocyte/macrophage-derived cell lines, stimulated with various endotoxins or the plaque forming peptide Abeta1-40. Moreover, CEP-1347 inhibited brain TNF production induced by intracerebroventricular injection of lipopolysaccharide in mice. As expected from a MLK inhibitor, CEP-1347 acted upstream of p38 and c-Jun activation in microglia by dampening the activity of both pathways. These data imply MLKs as important, yet unrecognized, modulators of microglial inflammation, and demonstrate a novel anti-inflammatory potential of CEP-1347.