Medical error and systems of signaling: conceptual and linguistic definition

In recent years the issue of patient safety has been the subject of detailed investigations, particularly as a result of the increasing attention from the patients and the public on the problem of medical error. The purpose of this work is firstly to define the classification of medical errors, which are distinguished between two perspectives: those that are personal, and those that are caused by the system. Furthermore we will briefly review some of the main methods used by healthcare organizations to identify and analyze errors. During this discussion it has been determined that, in order to constitute a practical, coordinated and shared action to counteract the error, it is necessary to promote an analysis that considers all elements (human, technological and organizational) that contribute to the occurrence of a critical event. Therefore, it is essential to create a culture of constructive confrontation that encourages an open and non-punitive debate about the causes that led to error. In conclusion we have thus underlined that in health it is essential to affirm a system discussion that considers the error as a learning source, and as a result of the interaction between the individual and the organization. In this way, one should encourage a non-guilt bearing discussion on evident errors and on those which are not immediately identifiable, in order to create the conditions that recognize and corrects the error even before it produces negative consequences.     

Food choice in disorders of eating behavior: Correlations with the psychopathological aspects of the diseases

Eating disorders (ED) are characterized by alterations in food choice and in the quantity and quality of nutrient intake. In a population of 124 female patients with ED (anorexia nervosa restricting subtype [AN-R, n = 37]; AN bingeing-purging subtype [AN-BP, n = 18]; bulimia nervosa purging subtype [BN-P, n = 40]; and binge eating disorder [BED, n = 29]) and healthy age-matched controls ([C], n = 20) we compared food choice and macronutrient intake with psychopathologic symptoms of the disorders. Data were collected from the probands’ 7-day food diaries and the scores from two assessment scales (Eating Disorder Inventory-2 [EDI-2] and Temperament and Character Inventory-revised [TCI-R]) that measure symptom domains, dimensions of personality and character dimensions, respectively. Multiple regression analysis was applied to the nutritional data and scale scores. When compared to the values for the control group, intake of animal proteins (grams) was significantly lower for all patient groups, intake of lactoproteins was lower for the AN-R and AN-BP than BN-P and BED groups, intake of vegetal proteins was higher for the AN-R, AN-BP, BN-P and BED groups, intake of dietary fats was lower for the AN-R and AN-BP subtype groups, and intake of total carbohydrates and oligosaccharides was lower for the AN-R and AN-BP groups, and oligosaccharides also for the BED, when calculated in grams but not when expressed in percent. When studied as percent values animal proteins were lower in patients than in controls, lactoprotein in BN-P and BED, vegetal proteins higher in all the patients, fat lower in AN-R and AN-BP, while carbohydrates did not differ between patients and controls.     

Risk factors and clinical profile of thrombotic thrombocytopenic purpura in systemic lupus erythematosus patients. Is this a distinctive clinical entity in the thrombotic microangiopathy spectrum?: A case control study

Introduction

The association of thrombotic thrombocytopenic purpura (TTP) with systemic lupus erythematosus (SLE) is rare. It is associated with high morbidity and mortality. Information about risk factors and clinical outcomes is scant.

Material and Methods

A retrospective case-control study was performed in a referral center in Mexico City between 1994 and 2013. Patients were diagnosed with TTP if they fulfilled the following criteria: microangiopathic haemolytic anaemia, thrombocytopenia, high LDH levels, normal fibrinogen and negative Coombs’ test. Patients with SLE were diagnosed with ≥ 4 ACR criteria. We included three study groups: group A included patients with SLE-associated TTP (TTP/SLE; cases n = 22, TTP events n = 24); patients with non-autoimmune TTP (NA-TTP; cases n = 19, TTP events n = 22) were included in group B and patients with SLE without TTP (n = 48) in group C.

Results

After multivariate analysis, lymphopenia < 1000/mm3 [OR 19.84, p = 0.037], high SLEDAI score three months prior to hospitalisation [OR 1.54, p = 0.028], Hg < 7 g/dL [OR 6.81, p = 0.026], low levels of indirect bilirubin [OR 0.51, p = 0.007], and less severe thrombocytopenia [OR 0.98, p = 0.009] were associated with TTP in SLE patients. Patients with TTP/SLE received increased cumulative steroid dose vs. NA-TTP (p = 0.006) and a higher number of immunosuppressive drugs (p = 0.015). Patients with TTP/SLE had higher survival than NA-TTP (p = 0.033); however, patients hospitalised for TTP/SLE had a higher risk of death than lupus patients hospitalised for other causes

Conclusions

Lymphopenia is an independent risk factor for TTP/SLE. It is likely that patients with TTP/SLE present with less evident clinical features, so the level of suspicion must be higher to avoid delay in treatment.     

Structure and backbone dynamics of a microcrystalline metalloprotein by solid-state NMR

We introduce a new approach to improve structural and dynamical determination of large metalloproteins using solid-state nuclear magnetic resonance (NMR) with (1)H detection under ultrafast magic angle spinning (MAS). The approach is based on the rapid and sensitive acquisition of an extensive set of (15)N and (13)C nuclear relaxation rates. The system on which we demonstrate these methods is the enzyme Cu, Zn superoxide dismutase (SOD), which coordinates a Cu ion available either in Cu(+) (diamagnetic) or Cu(2+) (paramagnetic) form. Paramagnetic relaxation enhancements are obtained from the difference in rates measured in the two forms and are employed as structural constraints for the determination of the protein structure. When added to (1)H-(1)H distance restraints, they are shown to yield a twofold improvement of the precision of the structure. Site-specific order parameters and timescales of motion are obtained by a gaussian axial fluctuation (GAF) analysis of the relaxation rates of the diamagnetic molecule, and interpreted in relation to backbone structure and metal binding. Timescales for motion are found to be in the range of the overall correlation time in solution, where internal motions characterized here would not be observable.     

Murine gammaherpesvirus 68 infection protects lupus-prone mice from the development of autoimmunity

Gammaherpesvirus infections, such as those caused by EBV, have been suggested to promote the development of autoimmunity. To test this idea, we infected healthy WT and lupus-prone B6.Sle123 mice with an EBV-related and rodent-specific gammaherpesvirus, γHV68. Although acute γHV68 infection increased autoantibody levels for 4 to 6 wk, latent infection inhibited these responses for 1 y. The inhibition of autoantibody expression was only observed in B6.Sle123 females and not in males, which already displayed lower autoantibody titers. Contrary to the initial hypothesis, infection of young B6.Sle123 mice, both male and female, resulted in suppression of lymphoid activation and expansion and of glomerular inflammation and sclerosis, preserving kidney function. Moreover, γHV68 infection led to reduced autoantibody titers, lymphoid activation, and glomerular inflammation whether lupus-prone females were infected before or during disease manifestation. Finally, γHV68 infection also inhibited autoantibody production in the genetically distinct MRL/lpr lupus-prone mice. Our findings indicate that γHV68 infection strongly inhibits the development and progression of lupus-like disease in mice that spontaneously develop this condition mediating its beneficial effects at the humoral, cellular, and organ levels. The mechanisms by which the virus exerts this down-modulatory action are not yet clear, but appear to operate via reduced activation of dendritic cells, T cells, and B cells. Gammaherpesviruses coevolved with the vertebrate immune systems, establishing lifelong infections in humans and other mammals. Our findings that γHV68 infection prevents rather than exacerbates autoimmunity in mice suggest that infection with gammaherpesviruses may be protective rather than pathological in most individuals.     

Phase II study of sorafenib in patients with relapsed or refractory lymphoma

The safety and activity of the multikinase inhibitor sorafenib were investigated in patients with relapsed or refractory lymphoproliferative disorders who received sorafenib (400 mg) twice daily until disease progression or appearance of significant clinical toxicity. The primary endpoint was overall response rate (ORR). Biomarkers of sorafenib activity were analysed at baseline and during treatment. Thirty patients (median age, 61 years; range, 18-74) received a median of 4 months of therapy. Grade 3-4 toxicities included hand/foot skin reactions (20%), infections (12%), neutropenia (20%) and thrombocytopenia (14%). Two patients achieved complete remission (CR), and two achieved partial remission (PR) for an ORR of 13%. Stable disease (SD) and progressive disease (PD) was observed in 15 (50%) and 11 patients (37%), respectively. The median overall survival (OS) for all patients was 16 months. For patients who achieved CR, PR and SD, the median time to progression and OS was 5 and 24 months, respectively. Compared with patients with PD, responsive patients had significantly higher baseline levels of extracellular signal-regulated kinase phosphorylation and autophagy and presented a significant reduction of these parameters after 1 month of therapy. Sorafenib was well tolerated and had a clinical activity that warrants development of combination regimens.