[Effectiveness of an intervention to improve safety culture. Less is more?] / Efectividad de una intervención para mejorar la cultura de seguridad. ¿Menos es más?

OBJECTIVE: To assess the impact of a long-term initiative to improve safety culture among professionals working in a Health Area, and to know their perceived usefulness. MATERIAL AND METHODS: An uncontrolled intervention study was designed in a public health care organization including a 3rd level hospital and 5,000 professionals. To measure the impact, the AHRQ Survey was conducted by telephone. A total of 7 dimensions of culture were measured, before starting the project (2012, n=100) and 3 years later (2015, n=207). Variations between 2012 and the respondents aware of the project in 2015 (RAP) were compared, as also between this last group and the rest of respondents (RNAP). The utility was assessed using a 5-item Likert scale, defining higher utility by medians 4 or higher. RESULTS: The response rates were above 80%. In 2015, the 41.5% of respondents were RAP (95%CI: 34.8-48.3), which was perceived as of high utility. Negative variations were detected in "sense of security" (-9.9%, P<.01, vs. 2012, and -4.2% between 2015 groups) and "feedback and communication errors" (-10.0% vs. 2012, and -8.9% between 2015 groups, P<.05). There was a not-significant positive variation in "openness in communication" (1.3% vs. 2012, and 6.9% between 2015 groups). The "management support" showed a not-significant improve in 2015 (37.0%, 95%CI: 30.9-43.1, in RAP; and 38.3%, 95%CI: 33.1-43.4, in RANP) in comparison to 2012 (31.4%, 95%CI: 28.4-39.7). CONCLUSIONS: A paradoxical worsening is detected in several dimensions, this probably due to immaturity of the organization and the instrument used. Thus, tools explicitly considering the degree of maturity may be more appropriate to measure cultural changes, although more studies are needed.

Rewiring of the apoptotic TGF-ß-SMAD/NFκB pathway through an oncogenic function of p27 in human papillary thyroid cancer.

Papillary thyroid carcinoma (PTC), the most frequent thyroid cancer, is characterized by low proliferation but no apoptosis, presenting frequent lymph-node metastasis. Papillary thyroid carcinoma overexpress transforming growth factor-beta (TGF-ß). In human cells, TGF-ß has two opposing actions: antitumoral through pro-apoptotic and cytostatic activities, and pro-tumoral promoting growth and metastasis. The switch converting TGF-ß from a tumor-suppressor to tumor-promoter has not been identified. In the current study, we have quantified a parallel upregulation of TGF-ß and nuclear p27, a CDK2 inhibitor, in samples from PTC. We established primary cultures from follicular epithelium in human homeostatic conditions (h7H medium). TGF-ß-dependent cytostasis occurred in normal and cancer cells through p15/CDKN2B induction. However, TGF-ß induced apoptosis in normal and benign but not in carcinoma cultures. In normal thyroid cells, TGF-ß/SMAD repressed the p27/CDKN1B gene, activating CDK2-dependent SMAD3 phosphorylation to induce p50 NFκB-dependent BAX upregulation and apoptosis. In thyroid cancer cells, oncogene activation prevented TGF-ß/SMAD-dependent p27 repression, and CDK2/SMAD3 phosphorylation, leading to p65 NFκB upregulation which repressed BAX, induced cyclin D1 and promoted TGF-ß-dependent growth. In PTC samples from patients, upregulation of TGF-ß, p27, p65 and cyclin D1 mRNA were significantly correlated, while the expression of the isoform BAX-ß, exclusively transcribed in apoptotic cells, was negatively correlated. Additionally, combined ERK and p65 NFκB inhibitors reduced p27 expression and potentiated apoptosis in thyroid cancer cells while not affecting survival in normal thyroid cells. Our results therefore suggest that the oncoprotein p27 reorganizes the effects of TGF-ß in thyroid cancer, explaining the slow proliferation but lack of apoptosis and metastatic behavior of PTC.

[Sociodemographic characteristics and geographic variability associated with patient satisfaction in Primary Care]. / Características sociodemográficas y variabilidad geográfica relacionada con la satisfacción del paciente en Atención Primaria.

BACKGROUND: Patient satisfaction with health services plays an important role in programs to improve the quality of care from the point of view of users. The objectives of this study were: To identify sociodemographic characteristics associated with patient satisfaction in the care provided by family doctors in Primary Health Care (PHC) centres, and describe the geographical variability of this phenomenon in the Spanish National Health Service. MATERIAL AND METHODS: The data come from the European Health Survey (2009). Prevalence ratios (crude and adjusted) of the characteristics associated with both excellent satisfaction and dissatisfaction using Poisson regression, and their geographical variability are discussed. RESULTS: About one in every 3 users of the PHC believes that the care provided was excellent, while 6.7% were dissatisfied. There is a wide variability in the perception of satisfaction among the various regional health services, with prevalence ranging between 10.9% and 55.2%. Moreover, this assessment is closely related to age, level of self-perceived health, mental health, previous hospitalisation, chronic disease status, and limitations in daily activities. CONCLUSIONS: Satisfaction with the care provided by the PHC physician is relatively high. However, the distribution between regions and socio-demographic characteristics and health status of the user is heterogeneous.

Direct promoter induction of p19Arf by Pit-1 explains the dependence receptor RET/Pit-1/p53-induced apoptosis in the pituitary somatotroph cells.

Somatotrophs produce growth hormone (GH) and are the most abundant secretory cells of the pituitary. Somatotrophs express the transcription factor Pit-1 and the dependence receptor RET, its co-receptor GFRa1 and ligand GDNF. Pit-1 is a transcription factor essential for somatotroph proliferation and differentiation and for GH expression. GDNF represses excess Pit-1 expression preventing excess GH. In the absence of GDNF, RET behaves as a dependence receptor, becomes intracellularly processed and induces strong Pit-1 expression leading to p53 accumulation and apoptosis. How accumulation of Pit-1 leads to p53 expression is unknown. We have unveiled the relationship of Pit-1 with the p19Arf gene. There is a parallel correlation of RET processing, Pit-1 increase and ARF protein and mRNA expression. Interfering the pathway with RET, Pit-1 or p19Arf siRNA blocked apoptosis. We have found a Pit-1 DNA-binding element within the ARF promoter. Pit-1 directly regulates the CDKN2A locus and binds to the p19Arft promoter inducing p19Arf gene expression. The Pit-1-binding element is conserved in rodents and humans. RET/Pit-1 induces p19Arf/p53 and apoptosis not only in a somatotroph cell line but also in primary cultures of pituitary somatotrophs, where ARF siRNA interference also blocks p53 and apoptosis. Analyses of the somatotrophs in whole pituitaries supported the above findings. Thus Pit-1, a differentiation factor, activates the oncogene-induced apoptosis (OIA) pathway as oncogenes exerting a tight control in somatotrophs to prevent the disease due to excess of GH (insulin-resistance, metabolic disease, acromegaly).