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Treadmill Measured vs. Questionnaire Estimated Changes in Walking Ability in Patients With Peripheral Artery Disease
Full text linkOBJECTIVE: Determining the maximum walking time (MWT) using the treadmill test is the gold standard method for evaluating walking capacity and treatment effect in patients with peripheral arterial disease (PAD). However, self reported functional disability is important when assessing quality of life. Changes in the Walking Estimated Limitation Calculated by History (WELCH) questionnaire scores were compared with the MWT.
METHODS: A cross sectional study was performed in patients with intermittent claudication. The treadmill test (3.2 km/h; 10% gradient) and WELCH questionnaire were administered to all patients for objective evaluation of walking capacity. Given the log normal distribution of these parameters in patients with PAD, a log transformation was applied to the WELCH score (LnW) and maximum walking time (LnT). The responsiveness of the WELCH score was determined using mean changes and correlation coefficients of LnW and LnT changes. The effect of time on the "estimated minus real" (E - R) changes (LnW - change minus LnT - change) was assessed after categorisation of patients into various test-retest intervals. Patients who underwent lower limb revascularisation between the two tests and those who underwent medical treatment only were analysed.
RESULTS: Correlation coefficients between LnW and LnT for tests 1 and 2 were r = 0.514 and r = 0.503, respectively (p < .001, for both). Correlation for LnW change vs. LnT change was 0.384 (p < .001). E - R was positive only early after surgery. E - R was negative for all test-retest intervals >1 year in revascularised and non-revascularised patients.
CONCLUSION: Changes in WELCH scores correlated with changes observed on the treadmill in patients with intermittent claudication. For long test-retest intervals, WELCH changes tended to overestimate the worsening of walking impairment as compared with the measured difference observed in both revascularised and non-revascularised patients. A shortlived "honeymoon" (overestimation of the benefit for the shortest test-retest interval) was observed only in revascularised patients
Impact of body mass index on post-thyroidectomy morbidity
Full text linkBACKGROUND: The impact of obesity on total thyroidectomy (TT) morbidity (recurrent laryngeal nerve palsy and hypocalcaemia) remains largely unknown.
METHODS: In a prospective study (NCT01551914), patients were divided into five groups according to their body mass index (BMI): underweight, normal weight, overweight, obese, and severely obese. Preoperative and postoperative serum calcium was measured. Recurrent laryngeal nerve (RLN) function was evaluated before discharge, and if abnormal, at 6 months.
RESULTS: In total 1310 patients were included. Baseline characteristics were similar across BMI groups except for age and sex. Postoperative hypocalcaemia was more frequent in underweight compared to obese patients but the difference was not statistically significant in multivariate analysis. There was no difference between groups in terms of definitive hypocalcaemia, transient and definitive RLN palsy, and postoperative pain.
CONCLUSION: Obesity does not increase intraoperative and postoperative morbidity of TT, despite a longer duration of the procedure
Les immunothérapies spécifiques dans le traitement des cancers
Full text linkThe offer of anti-cancer drugs has recently been disrupted by the introduction of checkpoint inhibitors on the market. Currently, one anti-CTLA-4, two anti-PD-1 and two anti-PD-L1 are authorized in the European Union, in seven different types of cancer. The clinical development of these therapies is still in full swing: in July 2017, more than 1 500 clinical trials were evaluating anti-PD-1, anti-PD-L1 and anti-CTLA-4 drugs in about twenty different locations and this number continues to increase. In the short term in France, other immunotherapies, the CAR-T cells, will complete this therapeutic arsenal. These immunotherapies appear as a real revolution in the treatment of some cancers. Nevertheless, many issues are associated with these therapies, particularly regarding the identification of good responders, the proper use of these drugs including the management of therapeutic strategies and safety profile, as well as the organization of care. In addition, the expenses associated with ipilimumab, nivolumab and pembrolizumab are substantial and almost tripled in one year, going from 120 million euros in 2015 to more than 340 million euros in 2016. This raises the question of the ability of the current healthcare system to maintain equitable access to innovation and best treatments for all patients. For all these reasons, the French National Cancer Institute decided to dedicate its thematic annual report on these innovative immunotherapies, targeting in particular checkpoint inhibitors and CAR-T cells, in order to produce an inventory of current data and an analysis regarding the different issues associated with these therapies
The GLP-1 Receptor Agonist Exenatide Ameliorates Bone Composition and Tissue Material Properties in High Fat Fed Diabetic Mice
Full text linkType 2 diabetes mellitus (T2DM) has recently been recognized as a significant risk factor for bone fragility. Careful investigations of bone mechanical properties in human studies suggested possible alterations of bone composition, although this axis has poorly been investigated. The main aim of this study was to evaluate the impact of high fat diet-induced diabetes and therapy using the clinically approved GLP-1 receptor agonist, exenatide, on tissue bone mechanical properties and compositional parameters. Male mice had free access to high fat diet for 16 weeks to induce diabetes prior to commencement of the study. Exenatide was administered twice daily by i.p. injection at a dose of 25 nmol/kg for 52 days. Normal and high fat diet fed (HFD) mice injected with saline were used as controls. Bone mechanical properties was assessed at the organ level by 3-point bending and at the tissue level by nanoindentation. Bone microarchitecture was investigated by microcomputed tomography and bone composition was evaluated by Fourier transform infrared imaging. HFD mice exhibited profound alterations of bone mechanical properties at both the organ and tissue level. Collagen maturity as well as trabecular and cortical bone microarchitectures were abnormal. Administration of exenatide, led to clear ameliorations in bone mechanical properties at the organ and tissue levels by modifications of both cortical microarchitecture and bone compositional parameters (collagen maturity, mineral crystallinity, carbonate/phosphate ratio, acid phosphate content). These results bring new light on the mode of action of exenatide in bone physiology and demonstrate the value of GLP-1 mimetics in the treatment of fragility fractures in diabetes
Donner et conserver la maîtrise du bien donné : de la donation comme acte de prévision
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Effects of mean arterial pressure on arousal in sedated ventilated patients with septic shock: a SEPSISPAM post hoc exploratory study
Full text linkBACKGROUND: It is unknown whether the recommended mean arterial pressure (MAP) target of 65 mmHg during initial resuscitation of septic shock is sufficient to maintain cerebral perfusion. Thus, we tested the hypothesis that a higher MAP target in patients with septic shock may improve level of arousal.
METHODS: We performed a post hoc exploratory analysis of the SEPSISPAM trial, which assessed the effect of a "high-target" level of MAP (80-85 mmHg) versus the recommended "low-target" MAP (65-70 mm Hg) on mortality in patients with septic shock. Among the 776 patients originally recruited in SEPSISPAM trial, we selected those who were mechanically ventilated and sedated and with available evaluation of arousal level assessed by the Richmond Agitation and Sedation Scale (RASS).
RESULTS: We restricted our analysis to the period in which patients were treated with vasoactive drugs. Cumulative sedative drugs were assessed daily. A total of 532 patients were included in this study: 253 (47.6%) in the low-target group and 279 (52.4%) in the high-target group. Daily cumulative sedative drugs were similar in both groups. Compared to the low-target group, minimal and maximal RASS were significantly higher in the high-target group at day 2, 4 and 5. Furthermore, in order to consider the fact that multiple measures were done for each patient and to consider the global effect of time on these measures, we used a mixed linear regression and multivariate models: we confirmed that maximal RASS values were significantly higher in the high-target group.
CONCLUSION: In patients with septic shock who were mechanically ventilated and sedated, resuscitation with MAP target between 80 and 85 mmHg was associated with higher arousal level as compared to a MAP target between 65 and 70 mmHg