Quality of life and cost-effectiveness analysis of topical tranexamic acid and fibrin glue in femur fracture surgery.

BACKGROUND: We assessed quality of life (QoL) of patients undergoing surgery for proximal femur fracture and performed a cost-effectiveness analysis of haemostatic drugs for reducing postoperative bleeding. METHODS: We analysed data from an open, multicentre, parallel, randomized controlled clinical trial (RCT) that assessed the efficacy and safety of tranexamic acid (TXA group) and fibrin glue (FG group) administered topically prior to surgical closure, compared with usual haemostasis methods (control group). For this study we conducted a cost-effectiveness analysis of these interventions from the Spanish Health System perspective, using a time horizon of 12 months. The cost was reported in $US purchasing power parity (USPPP). We calculated the incremental cost-effectiveness ratio (ICER) per QALY (quality-adjusted life-year). RESULTS: We included 134 consecutive patients from February 2013 to March 2015: 42 patients in the TXA group, 46 in the FG group, and 46 in the control group. Before the fracture, EuroQol visual analogue scale (EQ-VAS) health questionnaire score was 68.6. During the 12 months post-surgery, the intragroup EQ-VAS improved, but without reaching pre-fracture values. There were no differences between groups for EQ-VAS and EuroQol 5 dimensions 5 levels (EQ-5D-5L) health questionnaire score, nor in hospital stay costs or medical complication costs. Nevertheless, the cost of one FG treatment was significantly higher (399.1 $USPPP) than the cost of TXA (12.9 $USPPP) or usual haemostasis (0 $USPPP). When comparing the cost-effectiveness of the interventions, FG was ruled out by simple dominance since it was more costly (13,314.7 $USPPP) than TXA (13,295.2 $USPPP) and less effective (utilities of 0.0532 vs. 0.0734, respectively). TXA compared to usual haemostasis had an ICER of 15,289.6 $USPPP per QALY). CONCLUSIONS: There were no significant differences between the intervention groups in terms of postoperative changes in QoL. However, topical TXA was more cost-effective than FG or usual haemostasis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02150720. Date of registration 30/05/2014. Retrospectively registered.

Socio-economic impact on women diagnosed and treated for breast cancer: a cross-sectional study.

INTRODUCTION: The increase in breast cancer survival poses a challenge for patients to be able to rejoin their professional and social life in very similar conditions to those before diagnosis. The aim of this study is to assess short- and medium-term social, economic and professional impact of BC among women diagnosed with it. METHODS: A cross-sectional descriptive study using QLQ-C30, QLQ-BR23, and MOS-SSS instruments and a semi-structured interview in women diagnosed in years 2011, 2014, and 2016 in Hospital de la Santa Creu i Sant Pau in Barcelona (Spain). RESULTS: 175 patients were included with a mean age of 55. About 62.8% were married or coupled, 76% were living with their family unit, and 52.6% denied changes in their living situation. The mean Support Global Index was 74.7% and 78.8% before and after diagnosis, respectively. The mean global quality of life (QOL) was 67.3%, outstanding insomnia as the main symptom (X > 30%) and sexual function as the most affected dimension. At the moment of diagnosis, two-thirds of patients were working. After diagnosis, 87.5% stopped working, 39.4% were off work for 7-12 months, and only 50% returned to work. Multivariate analysis identified working as the most associated variable with a good QOL. CONCLUSIONS: QOL among women diagnosed with breast cancer is quite high and stable. Nevertheless, there are some very relevant aspects to QOL that need to be considered whilst caring for patients with BC to achieve rehabilitation as complete and comprehensive as possible.

Rin1 is a negative regulator of the IL3 receptor signal transduction pathways.

Cytokines interact with cell-surface receptors, initiating signaling cascades that promote cell growth while inhibiting the pathways of apoptotic cells. Rin1 is a multifunctional protein that has been shown to regulate EGF receptor signaling and endocytosis. To examine the role of Rin1 in IL3 receptor signaling pathways, Rin1 and deletion mutants were expressed in cells using a retrovirus system. In this study, the overexpression of Rin1 molecules was shown to selectively block IL-3 activation of the Ras-Erk1/2 and PI3K/Akt pathways and the IL-3-stimulated incorporation of [3H] thymidine into DNA without a significant effect on the activity of the JNK and p38K pathways. Moreover, the depletion of Rin1 by RNA interference induced cell growth. In addition, Rin1 was also required as a downstream effector of BCR/ABL-induced cell proliferation. Interestingly, the expression of Rin1 selectively blocked the activation of Erk1/2 induced by the BCR/ABL oncogene. These results demonstrate that Rin1 plays an essential and selective role in both IL3- and BCR/ABL-induced cell proliferation and highlight a new function for Rin1 in leukemic cells.

Rin1 regulates insulin receptor signal transduction pathways.

Rin1 is a multifunctional protein containing several domains, including Ras binding and Rab5 GEF domains. The role of Rin1 in insulin receptor internalization and signaling was examined by expressing Rin1 and deletion mutants in cells utilizing a retrovirus system. Here, we show that insulin-receptor-mediated endocystosis and fluid phase insulin-stimulated endocytosis are enhanced in cells expressing the Rin1:wild type and the Rin1:C deletion mutant, which contain both the Rab5-GEF and GTP-bound Ras binding domains. However, the Rin1:N deletion mutant, which contains both the SH2 and proline-rich domains, blocked insulin-stimulated receptor-mediated and insulin-stimulated fluid phase endocytosis. In addition, the expression of Rin1:delta (429-490), a natural occurring splice variant, also blocked both receptor-mediated and fluid phase endocystosis. Furthermore, association of the Rin1 SH2 domain with the insulin receptor was dependent on tyrosine phosphorylation of the insulin receptor. Morphological analysis indicates that Rin1 co-localizes with insulin receptor both at the cell surface and in endosomes upon insulin stimulation. Interestingly, the expression of Rin1:wild type and both deletion mutants blocks the activation of Erk1/2 and Akt1 kinase activities without affecting either JN or p38 kinase activities. DNA synthesis and Elk-1 activation are also altered by the expression of Rin1:wild type and the Rin1:C deletion mutant. In contrast, the expression of Rin1:delta stimulates both Erk1/2 and Akt1 activation, DNA synthesis and Elk-1 activation. These results demonstrate that Rin1 plays an important role in both insulin receptor membrane trafficking and signaling.

Rab5-activating protein 6, a novel endosomal protein with a role in endocytosis.

Rab GTPases are regulators of membrane trafficking that cycle between active (GTP-bound) and inactive (GDP-bound) states. In this study, we report the identification of a new human Rab5 guanine nucleotide exchange factor (GEF), which we have named RAP6 (Rab5-activating protein 6). RAP6 contains a Rab5 GEF and a Ras GAP domain. We show that the Vps9 domain is sufficient for the interaction of RAP6 with GDP-bound Rab5 and that RAP6 stimulates Rab5 guanine nucleotide exchange. We also find that the Ras GAP domain of RAP6 shows GAP activity for Ras. Immunofluorescence experiments reveal that RAP6 is associated with plasma membrane and small intracellular vesicles that also contain Rab5. Additionally, the overexpression of RAP6 affects both fluid phase and receptor-mediated endocytosis. This study is the first to show that RAP6 is a novel regulator of endocytosis that exhibits GEF activity specific for Rab5 and GAP activity specific for Ras.

[Perinatal factors associated with attention deficit/hyperactivity diagnosis in Colombian Paisa children]. / Factores perinatales asociados con la aparición del trastorno por deficiencia de atención en niños de la comunidad colombiana 'paisa'.

INTRODUCTION: Some perinatal factors have been associated with attention d ficit/hyperactivity disorder (ADHD). OBJECTIVE: To estimate the association between perinatal factor and ADHD diagnosis in school, aged 6 to 11 years, children from Medell n city (Colombia). PATIENTS AND METHODS: A randomized sample of 200 cases, 6 to 11 year old, with standardized ADHD diagnosis was selected. A randomized sample of 200 control children, 6 to 11 year old, was selected from a data base of 70 schools of Medell n city. The same diagnostic protocol was administered to controls. A questionnaire with questions about pregnancy, delivery an neonatal period was given to the mothers. Data were analyzed using cross tabulation and stepwise logistic multiple regression analyses. RESULTS: Miscarriage symptoms, premature delivery symptoms, severe flu attacks (cold with fever, without virus confirmation), tobacco abuse, alcohol abuse (to become drunk), minor congenital malformations, neonatal seizures and hospitalizations during newborn period were factors associated with ADHD diagnosis (p< 0.05). However, stepwise logistic multiple regression analysis selected a block of variables formed by premature delivery symptoms, severe flu attacks and neonatal seizures as significant perinatal risk factors (p< 0.01) for ADHD diagnosis.

[Pancreatic pseudocyst, Torulopsis glabrata primary infection. Report of a case]. / Pseudoquiste de páncreas, infección primaria por Torulopsis glabrata. Reporte de un caso.

BACKGROUND: T. glabrata is a saprophyte fungus that has been considered in the past years to be a pathologic agent in the pancreatic pseudocyst. Only three cases have been reported in the world literature. OBJECTIVE: To present a new case of a patient with pancreatic pseudocyst whose primary cause of infection and sepsis was Torulopsis glabrata and to analyze the possible factors that produced the infection. In the same manner, a review of the cases on literature to date was conducted. CASE REPORT: We present the clinical evolution of a post surgical patient with conventional cholecystectomy with biliary duct exploration and biliary duct derivation secondary to choledocholithiasis. This patient developed acute pancreatitis days after an endoscopic retrograde cholangiopancreatography was carried out. The patient received wide-range antibiotics and total parenteral nutrition (TPN). Later, the patient's case was complicated with pancreatic pseudocyst that was act diagnosed and managed initially with antifungus therapy due to an asymptomatic stage and a late report for T. glabrata. CONCLUSIONS: Pancreatobiliary duct instrumentation, in the same manner, prolonged therapy with wide-spectrum antibiotics and with TPN an with the means that had associated as risk factors for T. glabrata infection. Therefore, this fungus could have changed its biologic behavior from commensal to pathogenic. A potentially pathogenic agent in patients receiving this type of therapy and who have pancreatic pseudocyst must be considered to recognize these in the initial stages and begin therapy.

Bedside management of lung collapse in children on mechanical ventilation: saline lavage--simulated cough technique proves simple, effective.

We report a simple, four-step procedure for bedside treatment of infants on mechanical ventilation who have various degree of lung collapse unresponsive to conventional instillation of saline followed by chest percussion with endotracheal suctioning. The technique involves hyperoxygenation by bagging with 100% oxygen, deep endotracheal instillation of 0.25-0.5 mL/kg sterile saline, bagging with momentary inspiratory hold, followed by release of the hold and simultaneous forced exhalation and vibration to simulate cough, and endotracheal suctioning. This procedure was repeated three to five times on the affected side and at least once on the unaffected side; it resulted in notably improved lung expansion in 48 of 57 infants, documented by chest radiographs. The 57 infants included 48 (84%) whose chest radiographs showed airways occluded by mucus ("no air bronchograms") and 7 (16%) whose chest radiographs showed patent airways ("air bronchograms"). The technique is less successful in the latter group of patients in whom material obstructing proximal and intermediate airways has already been removed or displaced to distal airways, or a parenchymal infection has developed.

Adenosine in the treatment of paroxysmal supraventricular tachycardia in children.

Intravenous bolus adenosine was given to four pediatric patients aged 1 month to 8 years who had paroxysmal supraventricular tachycardia that had not responded to conventional medical therapy. Adenosine (one to three doses) was successful in converting the arrhythmia to normal sinus rhythm in all four cases, and no side effects of the drug were noted.

Arterial thrombosis and protein S deficiency.

A previously healthy boy had progressive painful discoloration of the lower extremities and was treated with exchange transfusion and anticoagulation, which were unsuccessful in arresting pedal ischemia; amputation of all of the child's toes was required. Studies of the patient and his parents resulted in a diagnosis of inherited protein S deficiency.

Esophagotracheal perforation during an emergency intubation.

The authors report the first known case of a simultaneous esophagotracheal perforation, which occurred during an emergency intubation of a patient with airway abnormalities. The perforation was suspected from the postintubation chest roentgenograph and confirmed by fiber optic bronchoscopy which showed that the endotracheal tube had entered through the posterior wall of the trachea after perforating the esophagus. The patient had a tracheostomy done and was placed on prophylactic antibiotic therapy; the esophageal tear was left to heal spontaneously. Risk factors for esophagotracheal perforation, means to avoid it, and diagnosis and treatment considerations are discussed.

Dexamethasone in the prevention of postextubation stridor in children.

To assess whether there is any advantage in the use of corticosteroid to prevent postextubation stridor in children, we conducted a prospective, randomized, double-blind trial of dexamethasone versus saline solution. The patients were evaluated and then randomly selected to receive either dexamethasone or saline solution according to a stratification based on risk factors for postextubation stridor: age, duration of intubation, upper airway trauma, circulatory compromise, and tracheitis. Dexamethasone, 0.5 mg/kg, was given every 6 hours for a total of six doses beginning 6 to 12 hours before and continuing after endotracheal extubation in a pediatric intensive care setting. There was no statistical difference in incidence of postextubation stridor in the two groups; 23 of 77 children in the placebo group and 16 of 76 in the dexamethasone group had stridor requiring therapy (p = 0.21). We conclude that the routine use of corticosteroids for the prevention of postextubation stridor during uncomplicated pediatric intensive care airway management is unwarranted.

Early diaphragmatic paralysis. In infants with genetic disorders.

Three infants with recently diagnosed genetic diseases presented with respiratory failure and required assisted ventilation. One infant had spinal muscular atrophy (Werdnig-Hoffmann disease), and two had acid maltase deficiency. The cause of the respiratory failure in all was diaphragmatic paralysis, and they became ventilator dependent. Early diaphragmatic paralysis must be considered as a manifestation of genetic neuromuscular disorders.

Blunt cardiac injury in children.

Thirty-nine children admitted to the pediatric intensive care unit with multiple injuries from blunt trauma underwent serial EKGs, determination of creatinine phosphokinase (CPK) isoenzymes, echocardiography, and radionuclide angiography studies. Motor vehicle injuries were responsible for 83% (32 of 39) of admissions, the remainder (7 of 39) caused by falls from heights. Thirteen children sustained serious (Modified Injury Severity Score [MISS] greater than 25) multiple system injury. Chest injuries were sustained by 12 children, nine being serious thoracic injuries (MISS chest score greater than 2). Three children (7.7%) showed elevations of MB fraction of CPK isoenzymes in addition to EKG abnormalities and/or ejection fraction depression on radionuclide angiography and were considered to have sustained cardiac contusion. Eight other children (20%) had normal or borderline elevation of CPK-MB fraction and EKG abnormalities combined with abnormal echocardiograms or radionuclide angiograms, and were considered to have sustained cardiac concussion. An additional 14 children (36%) had EKG or radionuclide angiography abnormalities alone. Two children required lidocaine therapy for cardiac irritability manifesting as multifocal PVCs and ventricular tachycardia. Based on this study, a comprehensive diagnostic evaluation of the heart in all children sustaining multiple injuries from blunt trauma cannot be justified. Continuous cardiac monitoring should be initiated in the emergency room and maintained throughout intensive care unit confinement to identify transient dysrhythmias. In patients with significant dysrhythmias and in those with obvious thoracic injuries serial EKG and cardiac isoenzyme assay should be obtained. Dysrhythmias should be man-aged with appropriate anti-arrhythmic therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary edema complicating relief of upper airway obstruction.

Treatment by endotracheal intubation or tracheostomy in children with severe and prolonged upper airway obstruction usually results in dramatic improvement; in some rare instances, it is complicated by the development of pulmonary edema. During an eight-year period, the author observed this complication in 20 children. The mechanism of this edema is complex and not yet fully understood. In addition to hypoxia, profound hemodynamic changes occur during the inspiratory phase of the obstruction; highly negative transpulmonary pressure may lead to an increase in pulmonary blood volume and biventricular dysfunction, and possibly disruption of integrity of the pulmonary endothelium. These hemodynamic changes appear to be counterbalanced by the positive pleural and alveolar pressures and decreased venous return during the expiratory component of the obstruction. Nevertheless, when an artificial airway is inserted, this compensation is disrupted abruptly, resulting in an increase in systemic venous return and thus pulmonary edema. Although this type of edema usually is observed in cases of severe obstruction, it may go unrecognized or misdiagnosed.

Perforation of the heart by central venous catheters in infants: guidelines to diagnosis and management.

The frequent use of central venous catheters has resulted in improved monitoring and parenteral nutrition. However, these catheters have also been a source of numerous complications, some of them lethal. Two cases of perforation of the heart that resulted in cardiac tamponade and death are reported. Early detection of this complication depends on a high index of suspicion, both clinical and radiographic. Measures such as securing the catheter tip in the superior vena cava can prevent this complication; immediate evacuation of the pericardial fluid by gentle aspiration or pericardiocentesis can prove life-saving.