Modeling in-Hospital Patient Survival During the First 28 Days After Intensive Care Unit Admission: a Prognostic Model for Clinical Trials in General Critically Ill Patients

OBJECTIVE: The objective of the study was to develop a model for estimating patient 28-day in-hospital mortality using 2 different statistical approaches. DESIGN: The study was designed to develop an outcome prediction model for 28-day in-hospital mortality using (a) logistic regression with random effects and (b) a multilevel Cox proportional hazards model. SETTING: The study involved 305 intensive care units (ICUs) from the basic Simplified Acute Physiology Score (SAPS) 3 cohort. PATIENTS AND PARTICIPANTS: Patients (n = 17138) were from the SAPS 3 database with follow-up data pertaining to the first 28 days in hospital after ICU admission. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The database was divided randomly into 5 roughly equal-sized parts (at the ICU level). It was thus possible to run the model-building procedure 5 times, each time taking four fifths of the sample as a development set and the remaining fifth as the validation set. At 28 days after ICU admission, 19.98% of the patients were still in the hospital. Because of the different sampling space and outcome variables, both models presented a better fit in this sample than did the SAPS 3 admission score calibrated to vital status at hospital discharge, both on the general population and in major subgroups. CONCLUSIONS: Both statistical methods can be used to model the 28-day in-hospital mortality better than the SAPS 3 admission model. However, because the logistic regression approach is specifically designed to forecast 28-day mortality, and given the high uncertainty associated with the assumption of the proportionality of risks in the Cox model, the logistic regression approach proved to be superior.

Why and How Was Regionalization of Perinatal Care Accomplished in Portugal?

Portuguese health care system was created in 1979. It is universal and for free. Expenses are supported by the State through taxes. The modern perinatal care system started by the end of 1970. The first neonatal intensive care units were created in 1980, the Portuguese Neonatal Society in 1985 and the National Neonatal Transport System in 1987. Until the seventies of twentieth century and even during eighties there were more than 200 hospitals with deliveries, a great part without obstetrician or paediatrician, a great percentage of pregnancies had no prenatal care, there were few neonatal intensive care units and perinatal mortality rate was one of the highest in the European countries. In 1987 an Experts Committee was nominated by the Health Ministry aiming to collect and analyse data on perinatal care and to suggest improvements. The Report resulting from this work is the main document on which is based the reform. The reform was a 9 years program in 3 years stages aiming to close hospitals with less than 1500 deliveries/year, to reclassify hospitals, to create Coordinating Units between health centres and hospitals, to equip neonatal intensive and intermediate care units, to define needs of obstetricians, paediatricians and nurses for each centre and to promote specialised training in neonatology for paediatricians and nurses. Levels of perinatal care were defined as well as localization of each level of hospital according to the number of deliveries in one geographic area, geographic difficulties and existing routes and connections. Steps for opening and closure of different levels of hospitals were very well programmed. The organization, capacities, number of obstetricians, neonatologists and nurses as well as equipment for each level of care was defined. Rules for pregnant women and newborns transfer from level II to level III hospitals were also well described. A specific training is neonatology was created starting in 1990. This organization resulted in an impressive decrease in mortality rates at all levels and still it is the policy we have today.

Perinatal Care in Portugal: Effects of 15 Years of a Regionalized System

AIM: To share information on the organization of perinatal care in Portugal. METHODS: Data were derived from the Programme of the National Committee for Mother and Child Health 1989, National Institute for Statistics, and Eurostat. RESULTS: In 1989, perinatal care in Portugal was reformed: the closure was proposed of maternity units with less than 1500 deliveries per year; hospitals were classified as level I (no deliveries), II (low-risk deliveries, intermediate care units) or III (high-risk deliveries, intensive care units), and functional coordinating units responsible for liaison between local health centres and hospitals were established. A nationwide system of neonatal transport began in 1987, and in 1990 postgraduate courses on neonatology were initiated. With this reform, in-hospital deliveries increased from 74% before the reform to 99% after. Maternal death rate decreased from 9.2/100,000 deliveries in 1989 to 5.3 in 2003 and, in the same period, the perinatal mortality rate decreased from 16.4 to 6.6/1000 (live births + stillborn with > or = 22 wk gestational age), the neonatal mortality rate decreased from 8.1 to 2.7/1000 live births, and the infant mortality rate from 12.2/1000 live births to 4/1000. CONCLUSION: Regionalization of perinatal care and neonatal transport are key factors for a successful perinatal health system.

Acidentes em Crianças e Jovens, Que Contexto e Que Abordagem? Experiência de Nove Meses no Serviço de Urgência num Hospital de Nível II

Introdução: Os acidentes constituem uma importante causa de morbimortalidade infantil e de recurso ao serviço de urgência pediátrica. A nível nacional conhecem-se apenas alguns dados epidemiológicos. Métodos: Estudo observacional transversal com análise da coorte das crianças observadas no serviço de urgência pediátrica de um hospital nível II por motivo de acidente, durante um período de nove meses, com dados obtidos através de um inquérito e submetidos a análise estatística. Resultados: Das 22502 admissões de crianças até aos 14 anos registadas, 1746 (7,8%) foram por acidentes. A maioria era do sexo masculino e tinha mais de 5 anos. Os acidentes ocorreram maioritariamente no exterior da escola (29,1%) e interior de casa (25%), predominando a queda como tipo de acidente (55,5%) e a contusão como mecanismo de lesão (54,2%). A maioria das crianças (77,3%) foi submetida a exames complementares de diagnóstico destacando-se os radiológicos. Os diagnósticos mais frequentes foram os traumatismos superficiais (47,9%) e os ferimentos (24,8%). Em 6,6% (115) dos casos os acidentes foram considerados graves. Estas admissões por acidentes associaram-se a uma despesa imediata estimada de 124 mil euros. Discussão: A frequência elevada e o local de ocorrência dos acidentes coincidiram com a literatura. Apesar do predomínio das lesões minor superficiais (47,9%) verificou-se um número significativo de crianças com necessidade de cuidados hospitalares. Não foram registados óbitos. Os autores concluem que os acidentes em crianças foram um motivo frequente de ida ao serviço de urgência pediátrica com importante consumo de recursos. A sensibilização dos cuidadores é essencial na prevenção dos acidentes.

Mutilations Due to Medical Disorders in Children

Soft-tissue and bone necrosis, although rare in childhood, occasionally occur in the course of infectious diseases, either viral or bacterial, and seem to be the result of hypoperfusion on a background of disseminated intravascular coagulation. Treatment consists in correction of septic shock and control of necrosis. Necrosis, once started, shows extraordinarily rapid evolution, leading to soft-tissue and bone destruction and resulting in anatomic, functional, psychological, and social handicaps. Ten mutilated children were treated from January 1986 to January 1999 in Hospital de Dona Estefaˆ nia, Lisbon, Portugal. One was recovering from hemolytic-uremic syndrome with a severe combined immunodeficiency, another malnourished, anemic child had malaria, and three had chicken pox (in one case complicated by meningococcal septicemia). There were three cases of meningococcal and two of pyocyanic septicemia (one in a burned child and one in a patient with infectious mononucleosis). The lower limbs (knee,leg, foot) were involved in five cases, the face (ear, nose, lip) in four, the perineum in three, the pelvis (inguinal region, iliac crest) in two, the axilla in one, and the upper limb (radius, hand) in two. Primary prevention is based on early recognition of risk factors and timely correction. Secondary prevention consists of immediate etiologic and thrombolytic treatment to restrict the area of necrosis. Tertiary prevention relies on adequate rehabilitation with physiotherapy and secondary operations to obtain the best possible functional and esthetic result.

Continuous Infusion of Piperacillin/Tazobactam in Septic Critically Ill Patients - a Multicenter Propensity Matched Analysis

The clinical efficacy of continuous infusion of piperacillin/tazobactam in critically ill patients with microbiologically documented infections is currently unknown. We conducted a retrospective multicenter cohort study in 7 Portuguese intensive care units (ICU). We included 569 critically ill adult patients with a documented infection and treated with piperacillin/tazobactam admitted to one of the participating ICU between 2006 and 2010. We successfully matched 173 pairs of patients according to whether they received continuous or conventional intermittent dosing of piperacillin/tazobactam, using a propensity score to adjust for confounding variables. The majority of patients received 16g/day of piperacillin plus 2g/day of tazobactam. The 28-day mortality rate was 28.3% in both groups (p = 1.0). The ICU and in-hospital mortality were also similar either in those receiving continuous infusion or intermittent dosing (23.7% vs. 20.2%, p = 0.512 and 41.6% vs. 40.5%, p = 0.913, respectively). In the subgroup of patients with a Simplified Acute Physiology Score (SAPS) II>42, the 28-day mortality rate was lower in the continuous infusion group (31.4% vs. 35.2%) although not reaching significance (p = 0.66). We concluded that the clinical efficacy of piperacillin/tazobactam in this heterogeneous group of critically ill patients infected with susceptible bacteria was independent of its mode of administration, either continuous infusion or intermittent dosing.

Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: Four Years of Experience at a Reference Center

INTRODUCTION: We describe our center's initial experience with alcohol septal ablation (ASA) for the treatment of obstructive hypertrophic cardiomyopathy. The procedure, its indications, results and clinical outcomes will be addressed, as will its current position compared to surgical myectomy. OBJECTIVE: To assess the results of ASA in all patients treated in the first four years of activity at our center. METHODS: We retrospectively studied all consecutive and unselected patients treated by ASA between January 2009 and February 2013. RESULTS: In the first four years of experience 40 patients were treated in our center. In three patients (7.5%) the intervention was repeated. Procedural success was 84%. Minor complications occurred in 7.5%. Two patients received a permanent pacemaker for atrioventricular block (6% of those without previous pacemaker). The major complication rate was 5%. There were no in-hospital deaths; during clinical follow-up (22 ± 14 months) cardiovascular mortality was 2.5% and overall mortality was 5%. DISCUSSION AND CONCLUSION: The results presented reflect the initial experience of our center with ASA. The success rate was high and in line with published results, but with room to improve with better patient selection. ASA was shown to be safe, with a low complication rate and no procedure-related mortality. Our experience confirms ASA as a percutaneous alternative to myectomy for the treatment of symptomatic patients with obstructive hypertrophic cardiomyopathy refractory to medical treatment.

The Effect of Statins on Mortality in Septic Patients: a Meta-Analysis of Randomized Controlled Trials

OBJECTIVE: Statins are among the most prescribed drugs worldwide and their recently discovered anti-inflammatory effect seems to have an important role in inhibiting proinflammatory cytokine production, chemokines expression and counteracting the harmful effects of sepsis on the coagulation system. We decided to perform a meta-analysis of all randomized controlled trials ever published on statin therapy in septic patients to evaluate their effect on survival and length of hospital stay. DATA SOURCES AND STUDY SELECTION: Articles were assessed by four trained investigators, with divergences resolved by consensus. BioMedCentral, PubMed, Embase and the Cochrane Central Register of clinical trials were searched for pertinent studies. Inclusion criteria were random allocation to treatment and comparison of statins versus any comparator in septic patients. DATA EXTRACTION AND SYNTHESIS: Data from 650 patients in 5 randomized controlled studies were analyzed. No difference in mortality between patients receiving statins versus control (44/322 [14%] in the statins group vs 50/328 [15%] in the control arm, RR = 0.90 [95% CI 0.65 to 1.26], p = 0.6) was observed. No differences in hospital stay (p = 0.7) were found. CONCLUSIONS: Published data show that statin therapy has no effect on mortality in the overall population of adult septic patients. Scientific evidence on statins role in septic patients is still limited and larger randomized trials should be performed on this topic.

Hand, Foot, and Mouth Syndrome in an Immunocompetent Adult: a Case Report

BACKGROUND: Hand, foot, and mouth syndrome (HFMS) is a common acute illness. It is characterized by mild clinical symptoms including fever, blisters, and sores in the mouth and on the palms and soles following a 3- to 7-day incubation period. This syndrome is rarely seen in adults. CASE PRESENTATION: A 35-year-old male Caucasian patient had a history of multiple episodes of acute pharyngitis, hypertension, hypercholesterolemia, and occasional abdominal pain. He presented with polyarthralgia in the knees and hands and odynophagia, followed by fever, oral mucosal aphthous lesions, and vesicles on the palms and soles. Three weeks after presentation, he was admitted to the emergency room with acute myocarditis. The in-hospital evaluation revealed positive serology for coxsackie A9 (1:160), positive anti-transglutaminase and anti-gliadin antibodies, normal immunoglobulins, and human immunodeficiency virus negativity. CONCLUSION: We herein describe a case of HFMS that was associated with coxsackie A9 infection complicated by acute myocarditis. Although an association between celiac disease and HFMS has not been described, this patient's immunologic disruption could have favored the development of infection and ultimately HFMS.

Variant Rett Syndrome in a Girl with a Pericentric X-Chromosome Inversion Leading to Epigenetic Changes and Overexpression of the MECP2 Gene

Rett syndrome is a neurodevelopmental disorder caused by mutations in the MECP2 gene. We investigated the genetic basis of disease in a female patient with a Rett-like clinical. Karyotype analysis revealed a pericentric inversion in the X chromosome -46,X,inv(X)(p22.1q28), with breakpoints in the cytobands where the MECP2 and CDKL5 genes are located. FISH analysis revealed that the MECP2 gene is not dislocated by the inversion. However, and in spite of a balanced pattern of X inactivation, this patient displayed hypomethylation and an overexpression of the MECP2 gene at the mRNA level in the lymphocytes (mean fold change: 2.55±0.38) in comparison to a group of control individuals; the expression of the CDKL5 gene was similar to that of controls (mean fold change: 0.98±0.10). No gains or losses were detected in the breakpoint regions encompassing known or suspected transcription regulatory elements. We propose that the de-regulation of MECP2 expression in this patient may be due to alterations in long-range genomic interactions caused by the inversion and hypothesize that this type of epigenetic de-regulation of the MECP2 may be present in other RTT-like patients.

Validation of Two US Risk Scores for Percutaneous Coronary Intervention in a Single-Center Portuguese Population of Patients with Acute Coronary Syndrome

INTRODUCTION: New scores have been developed and validated in the US for in-hospital mortality risk stratification in patients undergoing coronary angioplasty: the National Cardiovascular Data Registry (NCDR) risk score and the Mayo Clinic Risk Score (MCRS). We sought to validate these scores in a European population with acute coronary syndrome (ACS) and to compare their predictive accuracy with that of the GRACE risk score. METHODS: In a single-center ACS registry of patients undergoing coronary angioplasty, we used the area under the receiver operating characteristic curve (AUC), a graphical representation of observed vs. expected mortality, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analysis to compare the scores. RESULTS: A total of 2148 consecutive patients were included, mean age 63 years (SD 13), 74% male and 71% with ST-segment elevation ACS. In-hospital mortality was 4.5%. The GRACE score showed the best AUC (0.94, 95% CI 0.91-0.96) compared with NCDR (0.87, 95% CI 0.83-0.91, p=0.0003) and MCRS (0.85, 95% CI 0.81-0.90, p=0.0003). In model calibration analysis, GRACE showed the best predictive power. With GRACE, patients were more often correctly classified than with MCRS (NRI 78.7, 95% CI 59.6-97.7; IDI 0.136, 95% CI 0.073-0.199) or NCDR (NRI 79.2, 95% CI 60.2-98.2; IDI 0.148, 95% CI 0.087-0.209). CONCLUSION: The NCDR and Mayo Clinic risk scores are useful for risk stratification of in-hospital mortality in a European population of patients with ACS undergoing coronary angioplasty. However, the GRACE score is still to be preferred.