Results of a 1-year quality-improvement process to reduce door-to-needle time in acute ischemic stroke with MRI screening.

OBJECTIVE: To determine the effects of a 1-year quality-improvement (QI) process to reduce door-to-needle (DTN) time in a secondary general hospital in which multimodal MRI screening is used before tissue plasminogen activator (tPA) administration in patients with acute ischemic stroke (AIS). METHODS: The QI process was initiated in January 2015. Patients who received intravenous (iv) tPA<4.5h after AIS onset between 26 February 2015 to 25 February 2016 (during implementation of the QI process; the "2015 cohort") were identified (n=130), and their demographic and clinical characteristics and timing metrics compared with those of patients treated by iv tPA in 2014 (the "2014 cohort", n=135). RESULTS: Of the 130 patients in the 2015 cohort, 120 (92.3%) of them were screened by MRI. The median DTN time was significantly reduced by 30% (from 84min in 2014 to 59min; P<0.003), while the proportion of treated patients with a DTN time≤60min increased from 21% to 52% (P<0.0001). Demographic and baseline characteristics did not significantly differ between cohorts, and the improvement in DTN time was associated with better outcomes after discharge (patients with a 0-2 score on the modified rankin scale: 59% in the 2015 cohort vs 42.4% in the 2014 cohort; P<0.01). During the 1-year QI process, the median DTN time decreased by 15% (from 65min in the first trimester to 55min in the last trimester; P≤0.04) with a non-significant 1.5-fold increase in the proportion of treated patients with a DTN time≤60min (from 41% to 62%; P=0.09). CONCLUSION: It is feasible to deliver tPA to patients with AIS within 60min in a general hospital, using MRI as the routine screening modality, making this QI process to reduce DTN time widely applicable to other secondary general hospitals.

Time, dose and ataxia telangiectasia mutated (ATM) status dependency of coding and noncoding RNA expression after ionizing radiation exposure.

Studies of gene expression have proved important in defining the molecular mechanisms of radiation action and identifying biomarkers of ionizing radiation exposure and susceptibility. The full transcriptional response to radiation is very complex since it also involves epigenetic mechanisms triggered by radiation exposure such as modifications of expression of noncoding RNA such as microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that have not been fully characterized. To improve our understanding of the transcriptional response to radiation, we simultaneously monitored the expression of ten protein-coding genes, as well as 19 miRNAs and 3 lncRNAs in a time- and dose-dependent manner in stimulated human T lymphocytes obtained from two healthy donors (C1 and C2) and one patient with ataxia telangiectasia (AT), which is a well characterized radiosensitivity disorder. After 2 Gy X irradiation, expression levels were monitored at time points ranging from 15 min up to 24 h postirradiation. The majority of genes investigated responded rapidly to radiation exposure, with the peak up-regulation (CDKN1A, SESN1, ATF3, MDM2, PUMA and GADD45A) or down-regulation (CCNB1) occurring 2-3 h postirradiation, while DDB2, FDXR and CCNG1 responded with slower kinetics reaching a peak of expression between 5 and 24 h. A significant modification of expression after radiation exposure was observed for miR-34a-5p and miR-182-5p, with an up-regulation occurring at late time points reaching two to threefold at 24 h. Differences between two donors in miR-182-5p response to radiation were detected: for C2, up-regulation reached a plateau-phase around 5 Gy, while for C1, up-regulation was at its maximum around 3 Gy and then decreased at higher doses. Among the three lncRNAs studied, TP53TG1 demonstrated a weak up-regulation, reaching a maximum of 1.5-fold at 24 h after radiation exposure. Conversely, FAS-AS1 was up-regulated up to fivefold by 5 Gy irradiation. Our results indicate that expression of the majority of protein-coding genes allows discrimination of the AT from healthy donors when analyzed at 2 h. However, differences in expression between AT and healthy donors are no longer detectable 24 h postirradiation although, interestingly, linear dose responses for some of the genes studied are obtained at this time point. Furthermore, our study shows that miRNAs miR-34a-5p and miR-182-5p are responsive to radiation exposure in a dose- and time-dependent manner. Additionally, to the best of our knowledge, this is the first study to report that FAS-AS1 lncRNA is up-regulated by radiation exposure in an ATM-dependent fashion in human T lymphocytes.

[Multiple sclerosis in Haute-Garonne: an important underestimation of case numbers]. / La SEP en Haute-Garonne : une sous-estimation importante du nombre de cas.

INTRODUCTION: In France, the prevalence of multiple sclerosis is estimated between 65 and 125 patients per 100,000 inhabitants with a South-West towards North-East gradient. Nevertheless, the epidemiology of multiple sclerosis remains still imperfectly known, the recent studies being realized, either in a region of France, or from a single data source and thus suscepted not to be exhaustive. OBJECTIVE: Assessing the prevalence of the multiple sclerosis in 2005 in Haute-Garonne by matching several data sources completed by a capture-recapture method; estimating the exhaustivity of each of the sources. METHODS: The data sources were hospital data (DRG for the hospitalization, data of consultation), data of public health insurance system (main health insurance, agricultural health insurance, social welfare for self employed), and data from the MIPSEP network. The linkage was based on name, maiden name, first name, date of birth and sex and allowed a first estimation of the number of cases. Models of loglinear regression allowed estimating the total number of case and the sensitivity of each source. RESULTS: The total number of cases obtained by matching several sources of information amounted to 1549. The use of several data sources increased by 25.6 % the maximum number of patients identified with a single source of information (national health insurance, any insurance). According to the model used, the method of capture-recapture estimated the number of cases up to 1722. Therefore, this study estimated a prevalence of multiple sclerosis between 110 and 149 cases per 100,000 inhabitants in Haute-Garonne. CONCLUSION: The prevalence of the multiple sclerosis is largely underestimated in Haute-Garonne and questions the magnitude over the so-called gradient. Matching several sources of information is indispensable to improve collection of the total number of cases.

Differences between poststroke drivers and nondrivers: demographic characteristics, medical status, and transportation use.

OBJECTIVE: To determine the demographic, medical, and transportation use characteristics of stroke survivors wanting to drive who resumed or did not resume driving and compare the driving habits of those who drove with those of a nonstroke control group. DESIGN: One hundred and six stroke survivors who underwent a driving evaluation at a rehabilitation center in Ottawa, Canada, between 1995 and 2003, participated in a structured telephone interview 4-5 yrs after the evaluation. Information on driving history and transportation use before the driving assessment was obtained from the driving assessment client database. The nonstroke control group was derived from the literature. RESULTS: After stroke, 66% of subjects had resumed driving. Prestroke driving history was similar for drivers and nondrivers. Drivers were younger than nondrivers (mean age +/- SD, 62.7 +/- 12.7 yrs vs. 69.2 +/- 13.4 yrs; P = 0.02), had less medical comorbidity (mean modified Cumulative Illness Rating Scale score, 3.7 +/- 1.97 vs. 5.0 +/- 2.89; P = 0.01), and were less likely to rely on a walker (1.4% vs. 19.4%, P < 0.001). Self-imposed restrictions were reported by 35.7% of drivers. More nondrivers than drivers relied on family/friends (94.4% vs. 41.4%), public transportation (60.7% vs. 35.3%), or taxis (27.8% vs. 2.9%) (all P < 0.05). Drivers reported fewer driving difficulties (e.g., skill, weather, or traffic related;

Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment.

Normal tissue reactions to radiation therapy vary in severity among patients and cannot be accurately predicted, limiting treatment doses. The existence of heritable radiosensitivity syndromes suggests that normal tissue reaction severity is determined, at least in part, by genetic factors and these may be revealed by differences in gene expression. To test this hypothesis, peripheral blood lymphocyte cultures from 22 breast cancer patients with either minimal (11) or very severe acute skin reactions (11) have been used to analyse gene expression. Basal and post-irradiation expression of four radiation-responsive genes (CDKN1A, GADD45A, CCNB1, and BBC3) was determined by quantitative real-time PCR in T-cell cultures established from the two patient groups before radiotherapy. Relative expression levels of BBC3, CCNB1, and GADD45A 2 h following 2 Gy X-rays did not discriminate between groups. However, post-irradiation expression response was significantly reduced for CDKN1A (P<0.002) in severe reactors compared to normal. Prediction of reaction severity of approximately 91% of individuals sampled was achieved using this end point. Analysis of TP53 Arg72Pro and CDKN1A Ser31Arg single nucleotide polymorphisms did not show any significant association with reaction sensitivity. Although these results require confirmation and extension, this study demonstrates the possibility of predicting the severity of acute skin radiation toxicity in simple tests.

[Dynamics of interdisciplinary around a health care network: simultaneous programme design and evaluation planning]. / Dynamique interdisciplinaire autour d'un réseau de soins: evaluer et construire en même temps.

This article reports on the evaluation experience of a multiple sclerosis care network in the Midi-Pyrénées region (MIPSEP). It shows how an evaluation team composed of public health doctors and sociologists progressively and naturally evolved from having a purely external observation role towards having a collaborative role actively working with the network's members and partners. A qualitative method was chosen for the data collection through interviews with the network's actors, and the frameworks for reference were constituted from official texts which defined the networks and their missions. Coming from a curative and healing culture, the network's actors were concerned primarily about how to organise themselves in order to better respond to the needs expressed by the patients. The various professional backgrounds and cultures, faced with different perspectives from innovation and confronted with the related difficulties, participated in a collective expertise exercise and collaborated in the construction process. This example supports an open, qualitative, evolutionary evaluation approach which is done in close proximity to the field and work on the ground. The study is timely given the current explosion of debate on evaluation methods. With a great deal of exchange and reflection on suitable tools and indicators as well as the respective roles of researchers, care givers and decision-makers, the results of this study advocate to favour multidisciplinary approaches, including opening up this process to funders and planning authorities rather than over-theorising about it, which only serves to enclose and paralyse a process that, on the contrary, should aim to be more inclusive. This could be a useful way to decompartmentalise and break down existing barriers within the health system.

[Explanatory factors of length of stay at the diagnosis-related group 129: common pneumonia and pleurisy, aged over 69 and/or associated co-morbidities]. / Facteurs explicatifs de la durée de séjour au sein du groupe homogène de malades 129: pneumonies et pleurésies banales, âge supérieur à 69 ans et/ou comorbidites associées.

BACKGROUND: Utilization of diagnosis related groups (DRGs) for hospital comparison, based on length of stay (LOS). OBJECTIVES: Inside a DRG (Pneumonia and pleurisy > 69 and/or associated comorbidities), to point out the explicative factors of LOS and the variables which could be recorded for a better description of these patients. SETTING: Pneumologic unit of Limoges' teaching hospital. METHODS: From 01-01-94 to 31-12-94, the DRG 129 was studied through the medical unit summary, the performance status at entrance, the social complexity, the characteristics of pneumonia (symptoms, temperature, arterial pressure...), the severity by American Thoracic Society (ATS) criteria, the procedures (chest X-ray, biology, fibroscopy...), the antibiotic treatments (intravenous and oral). Statistical tests associated univariate analysis, linear and logistic regressions. RESULTS: LOS was 15.53 d +/- 8.57 (m +/- SD). The mathematical model explains 69% of the variance of LOS logarithm. The logistic regression found 5 variables with a significant odds-ratio (OR) for an increased LOS: a high ATS score, repeated laboratory tests, a complex social situation, an increase length of antibiotic treatment (intravenous and oral). CONCLUSION: A better description of LOS, inside a DRG, needs supplementary variables. For pneumonia admitted in Limoges' hospital, the severity of the disease, the number of laboratory tests, the antibiotic treatment, the social complexity are the more significant indicators.