BMJ Open

OBJECTIVE: This study aims to evaluate whether the first wave of the COVID-19 pandemic resulted in a deterioration in the quality of care for socially and/or clinically vulnerable stroke and ST-segment elevation myocardial infarction (STEMI) patients. DESIGN: Two cohorts of STEMI and stroke patients in the Aquitaine neurocardiovascular registry. SETTING: Six emergency medical services, 30 emergency units, 14 hospitalisation units and 11 catheterisation laboratories in the Aquitaine region in France. PARTICIPANTS: This study involved 9218 patients (6436 stroke and 2782 STEMI patients) in the neurocardiovascular registry from January 2019 to August 2020. PRIMARY OUTCOME MEASURES: Care management times in both cohorts: first medical contact-to-procedure time for the STEMI cohort and emergency unit admission-to-imaging time for the stroke cohort. Associations between social (deprivation index) and clinical (age >65 years, neurocardiovascular history) vulnerabilities and care management times were analysed using multivariate linear mixed models, with an interaction on the time period (pre-wave, per-wave and post-first COVID-19 wave). RESULTS: The first medical contact procedure time was longer for elderly (p<0.001) and 'very socially disadvantaged' (p=0.003) STEMI patients, with no interaction regarding the COVID-19 period (age, p=0.54; neurocardiovascular history, p=0.70; deprivation, p=0.64). We found no significant association between vulnerabilities and the admission imaging time for stroke patients, and no interaction with respect to the COVID-19 period (age, p=0.81; neurocardiovascular history, p=0.34; deprivation, p=0.95). CONCLUSIONS: This study revealed pre-existing inequalities in care management times for vulnerable STEMI and stroke patients; however, these inequalities were neither accentuated nor reduced during the first COVID-19 wave. Measures implemented during the crisis did not alter the structured emergency pathway for these patients. TRIAL REGISTRATION NUMBER: NCT04979208

Stroke

Background and Purpose-The aim of the present study was to evaluate the relationship between normal-appearing white matter (NAWM) integrity and postischemic stroke recovery in 4 main domains including cognition, mood, gait, and dependency. Methods-A prospective study was conducted, including patients diagnosed for an ischemic supratentorial stroke on a 3T brain MRI performed 24 to 72 hours after symptom onset. Clinical assessment 1 year after stroke included a Montreal Cognitive Assessment, an Isaacs set test, a Zazzo cancelation task, a Hospital Anxiety and Depression scale, a 10-meter walking test, and a modified Rankin Scale (mRS). Diffusion tensor imaging parameters in the NAWM were computed using FMRIB (Functional Magnetic Resonance Imaging of the Brain) Diffusion Toolbox. The relationships between mean NAWM diffusion tensor imaging parameters and the clinical scores were assessed using linear and ordinal regression analyses, including the volumes of white matter hyperintensities, gray matter, and ischemic stroke as radiological covariates. Results-Two hundred seven subjects were included (66±13 years old; 67% men; median National Institutes of Health Stroke Scale score, 3; interquartile range, 2-6). In the models including only radiological variables, NAWM fractional anisotropy was associated with the mRS and the cognitive scores. After adjusting for demographic confounders, NAWM fractional anisotropy remained a significant predictor of mRS (β=-0.24; P=0.04). Additional path analysis showed that NAWM fractional anisotropy had a direct effect on mRS (β=-0.241; P=0.001) and a less important indirect effect mediating white matter hyperintensity burden. Similar results were found with mean diffusivity, axial diffusivity, and radial diffusivity. In further subgroup analyses, a relationship between NAWM integrity in widespread white matter tracts, mRS, and Isaacs set test was found in right hemispheric strokes. Conclusions-NAWM diffusion tensor imaging parameters measured early after an ischemic stroke are independent predictors of functional outcome and may be additional markers to include in studies evaluating poststroke recovery. © 2020 Lippincott Williams and Wilkins. All rights reserved.Translational Research and Advanced Imaging Laborator

Preoperative bi-fractionated accelerated radiation therapy for combined treatment of locally advanced rectal cancer in a consectutive series of unselected patients

Background: although preoperative RT (Radiation Therapy) is becoming the preferred approach for combined treatment of locally advanced rectal adenocarcinoma, no regimen can be now considered as a standard. Since the toxicity of preoperative RT isn't yet completely known, and the advantages of preoperative RT could be counterbalanced by increased postoperative morbidity and mortality, a monocentre series of preoperative bifractionated accelerated RT was retrospectively reviewed to clarify toxicity and outcomes after a prolonged follow up. Methods: patients were screened following these eligibility criteria: histology-proven adenocarcinoma of the rectum; distal tumour extent at 12 cm or less from the anal verge; clinical stage T3-4/anyN, or anyT/ N1-2; ECOG Performance Status 0-2. A total dose of 41.6 Gy (26 twice daily fractions of 1.6 Gy) was delivered. Surgery was carried out 17 \ub1 2 days after RT completion, adopting the total mesorectal excision technique. Results: 24 men and 23 women were enrolled; median age was 55 years (r.: 39-77). Twenty-eight patients were stage II and 19 stage III. 9 patients suffered from a recurrent tumour. 2 patients experienced a severe grade 4 gastrointestinal toxicity (a colo-vaginal fistula and an intestinal obstruction, both successfully treated). Operative mortality was nil; postoperative early complications occurred in 13 cases; mean length of hospital stay was 15 days. After a mean follow up of 44 months (r.: 18-84) 8 patients had deceased for recurrent disease, 15 were alive with a disease progression (2 pelvic recurrences and 13 pure distant deposits) and 24 were alive, without disease. The 5-year actuarial overall survival was 74.2%, the disease-free survival 62.9% and the regional control rate 84.7%. Long-term complications included 1 case of radiation enteritis requiring surgery, 2 cases of anastomotic stricture and 3 cases of bladder incontinence. Conclusion: bifractionated accelerated RT administered in the preoperative setting to patients bearing locally advanced rectal cancer is reliable and safe, as its immediate and late toxicity (mainly infectious) is acceptably low and long-term survivals are achievable. These findings support the increasing use of preoperative RT for treatment of this malignancy in experienced centres. Ongoing multicentric trials are expected to address still unsolved issues, including the benefit of CT adjunct to preoperative RT

Stat Methods Med Res

Mixed models estimated by maximum likelihood and marginal models estimated by generalized estimating equations are the standard methods for the analysis of longitudinal data. However, their use is highly debated when attrition may be due to death. While some authors consider that mixed model estimates are interpretable only in an immortal cohort, we show that their subject-specific interpretation still holds in the population currently alive, but their population-averaged interpretation is valid only in the immortal cohort. We propose an approximation of the population-averaged mean among the population alive that highlights the difference with the population-averaged mean in the immortal cohort. The interpretation of ML estimates of mixed models and joint models for the marker and the time-to-death as well as unweighted and weighted GEE of marginal models is then illustrated in a simulation study and in an application regarding cognitive decline in the elderly

Rev Epidemiol Sante Publique

Contexte et objectif : Lors d'un accident vasculaire cérébral ischémique dû à une occlusion d'un gros vaisseau, plus la thrombectomie mécanique (TM) est réalisée rapidement, meilleur est le pronostic fonctionnel. Cependant, l'organisation des soins ne permet pas systématiquement un accès rapide à la TM. L'objectif de notre étude était de déterminer les facteurs cliniques et organisationnels associés au délai d'accès à la TM. Méthodes : Nous avons réalisé une étude de cohorte dans le département de la Gironde, en France. Les patients nécessitant une TM et régulés par les Services d'Aide Médicale Urgente (SAMU) de Gironde entre le 01/01/2017 et le 31/12/2018 ont été inclus. Le délai d'accès à la TM correspondait à la différence entre le premier appel au SAMU et la ponction de l'aine pour TM. Les principales variables explicatives étaient : le type de parcours de soins (mothership (MS), drip and ship (DS) avec imagerie cérébrale réalisée au centre hospitalier de proximité (CHP) et DS sans imagerie au CHP) ; le score NIHSS ; la distance kilométrique pour accéder à la TM ; le moment de survenue de l'AVC (week-end ou jour férié, vacances scolaires, autre) ; l'âge et le sexe. Des modèles de régression linéaire ont été utilisés pour expliquer le délai d'accès à la TM. Les données manquantes ont été gérées à l'aide d'une procédure d'imputation multiple (spécification conditionnelle complète, Mice R-Package) exécutée dans notre modèle de régression linéaire multivariable. Une analyse quantitative du biais a été réalisée en pondérant le délai imputé d'accès à la TM et en identifiant le poids qui modifie les conclusions de notre analyse. Résultats : Parmi les 314 patients inclus, 152 étaient des femmes (48,4 %), et le score NIHSS moyen à l'admission était de 16,4. Deux cent deux (64,3 %) patients ont été pris en charge dans parcours MS. Le délai moyen entre le premier appel au SAMU et la ponction fémorale pour TM était de 251 minutes. Dans l'analyse multivariable, le délai d'accès à la TM était plus long lorsque les patients étaient pris en charge dans le parcours DS avec imagerie dans le CHP (+106 min, p=0,03), et encore plus long dans le parcourd DS sans imagerie dans le CHP (+197 min, p=0,002), par rapport au parcours MS. Le délai d'accès à la TM diminuait avec l'augmentation du score NIHSS (-6 min par point NIHSS, p<.0001). Dans notre analyse quantitative des biais, nous avons multiplié le délai imputé d'accès à la TM dans les parcours DS uniquement (avec ou sans imagerie dans le CHP) par des poids variant de 0,9 à 0,2 (délais imputés réduits de 10 % à 80 %). Avec une réduction de 40 % ou plus, il n'y avait plus de différence de délai d'accès à la TM entre les trois parcours de soins étudiés. Conclusions : Le parcours DS peut encore être raccourci en généralisant l'accès à l'imagerie cérébrale au sein des CHP. L'optimisation de l'orientation pré-admission vers la TM est un point majeur dans la prise en charge des accidents vasculaires cérébraux ischémiques dûs à une occlusion d'un gros vaisseau.BACKGROUND AND PURPOSE: When an ischaemic stroke due to a large vessel occlusion occurs, the sooner Mechanical Thrombectomy (MT) is performed, the better the functional prognosis. However, the organisation of care does not systematically allow rapid access to MT. The aim of our study was to determine the clinical and organisational factors associated with the time to access to MT. METHODS: We conducted a cohort study in Gironde County, France. Patients admitted for MT and regulated by the Gironde Emergency Medical Services (EMS) between 01/01/2017 and 31/12/2018 were included. The time to access to MT was the difference between the first call to EMS and groin puncture for MT. The main explanatory variables were: type of pathway (mothership (MS), drip and ship (DS) with cerebral imaging performed in the local hospital centre (LHC), and DS without imaging in the LHC); NIHSS score; driving distance to MT; time of stroke onset (weekend or holiday, school holidays, other); age and sex. Linear regression models were used to explain time to access to MT. Missing data were handled using a multiple imputation procedure (Full conditional specification, Mice R-Package) carried out in our multivariable linear regression model. A quantitative bias analysis was performed by weighing the imputed time to access to MT and identifying the weight changing the conclusions of our analysis. RESULTS: Among the 314 included patients, 152 were women (48.4%), and the mean NIHSS score was 16.4. Two hundred and two (64.3%) patients were managed through the MS pathway. The average time from onset to femoral puncture was 251 minutes. In the multivariate analysis, the time to MT was longer when patients were managed DS with imaging in the LHC pathway (+106 min, p = 0.03), and even longer in the DS without imaging in the LHC pathway (+197 min, p = 0.002), compared with MS. Time from onset to MT decreased with increasing NIHSS score (-6 min per NIHSS point, p <.0001). In our quantitative bias analysis, we multiplied the imputed time in access to MT in the DS pathways only (with or without imaging in the LHC) by weights varying from 0.9 to 0.2 (imputed delays reduced from 10% to 80%). With reduction of 40% or more, there was no longer any difference in time to access to MT between the three studied pathways. CONCLUSIONS: The DS pathway can be shortened by generalizing access to cerebral imaging in LHCs. Optimizing pre-admission orientation toward MT is a major issue in LVOS management

Rev Neurol

The objectives were to analyze changes from 2012 to 2017 in different management times of stroke patients included in the Aquitaine stroke Observatory (ObA2). The studied times (onset-to-needle time-ONT, onset-to-door time-ODT, door-to-imaging time-DIT, door-to-needle time-DNT and imaging-to-needle time-INT) were described as median, interquartile ranges and proportion of patients within the recommended median time goals (ODT under 4hours, DIT within 20min; for thrombolyzed patients, DIT under 20min and a ONT under 4:30) to be compared with an objective of 50% of patients within said time goal. Globally, ODT was 160min, with 43.6% to 59.6% of patients within the ODT goal along the study period. With no improvement over time, the proportion of patients within the DIT goal stayed stable and at a low level (range: 5.5-7.0%) for all patients, decreasing from 25.2% to 11.4% for thrombolyzed patients. The proportion of thrombolyzed patients within the DNT goal varied from 15.1% to 30.3% during study period. These results highlight the urgent need for action to improve in-hospital management of stroke patients, focusing on delays between admission and imaging

Imaged-guided liver stereotactic body radiotherapy using VMAT and real-time adaptive tumor gating. Concerns about technique and preliminary clinical results

BackgroundMotion management is a major challenge in abdominal SBRT. We present our study of SBRT for liver tumors using intrafraction motion review (IMR) allowing simultaneous KV information and MV delivery to synchronize the beam during gated RapidArc treatment.Materials and methodsBetween May 2012 and March 2015, 41 patients were treated by liver SBRT using gated RapidArc technique in a Varian Novalis Truebeam STx linear accelerator. PTV was created by expanding 5[[ce:hsp sp="0.25"/]]mm from the ITV. Dose prescription ranged from 40 to 50[[ce:hsp sp="0.25"/]]Gy in 5–10 fractions. The prescribed dose and fractionation were chosen depending on hepatic function and dosimetric results. Thirty-four patients with a minimal follow-up of six months were analyzed for local control and toxicity. Accuracy for tumor repositioning was evaluated for the first ten patients.ResultsWith a median follow-up of 13 months, the treatment was well tolerated and no patient presented RILD, perforation or gastrointestinal bleeding. Acute toxicity was found in 3 patients with G1 abdominal pain, 2 with G1 nausea, 10 with G1 asthenia and 1 with G2 asthenia. 6 patients presented asymptomatic transitory perturbation of liver enzymes.In-field local control was 90.3% with 7 complete responses, 14 partial responses and 7 stabilisations. 3 patients evolved “in field”. 12 patients had an intrahepatic progression “out of field”.Mean intrafraction deviation of fiducials in the craneo-caudal direction was 0.91[[ce:hsp sp="0.25"/]]mm (0–6[[ce:hsp sp="0.25"/]]mm).ConclusionThe clinical tolerance and oncological outcomes were favorable when using image-guided liver SBRT with real-time adaptive tumor gating

Rev Neurol (Paris)

BACKGROUND AND PURPOSE: Recent studies demonstrated the benefit of mechanical thrombectomy (MT) plus intravenous tissue-type plasminogen activator (IV-tPA) (MT-IV-tPA) in acute ischemic stroke. This study aimed to estimate the cost-utility of MT-IV-tPA compared with IV-tPA alone from the perspective of the French National Health Insurance. METHODS: We developed a decision tree for the first 3 months after stroke onset and a Markov model until 10 years post-stroke. The health states of the Markov model were according to the modified Rankin Scale (mRS): independent (mRS=0-2), dependent (mRS=3-5), dead (mRS=6). Recurrent stroke was the fourth health stage of our model. We conducted systematic literature reviews and meta-analyses to estimate the cost and utility of each health state, and the transition probabilities between health states. A microcosting study was conducted to estimate the cost of MT. We estimated the incremental cost-effectiveness ratio of MT-IV-tPA and conducted a probabilistic analysis in order to estimate the probability that MT-IV-tPA is cost-effective compared to IV-tPA, the expected value of perfect information (EVPI), and the expected value of partial perfect information (EVPPI), given the uncertainty surrounding the value of our model's parameters. RESULTS: The total mean (standard deviation (SD) cost of MT was euro6708.9 (2357.0). The incremental cost-effectiveness ratio (ICER) of the strategy using IV-tPA combined to MT costs was euro14,715 per QALY gained as compared to a strategy using IV-tPA alone. The probabilistic analysis showed that the probability of MT-IV-TPA being cost-effective was 85.4% at threshold willingness-to-pay of euro30,000 per QALY gained, reaching 98% at euro50,000 per QALY gained. CONCLUSION: Although there is no universally accepted willingness-to-pay threshold in France, our analysis suggest that MT combined to IV-tPA can be considered a cost-effective treatment compared with IV-tPA alone

Sequelae and Quality of Life in Patients Living at Home 1 Year After a Stroke Managed in Stroke Units

International audienceIntroduction: Knowledge about residual deficiencies and their consequences on daily life activities among stroke patients living at home 1-year after the initial event managed in stroke units is poor. This multi-dimensional study assessed the types of deficiencies, their frequency and the consequences that the specific stroke had upon the daily life of patients.Methods: A cross-sectional survey, assessing, using standardized scales, 1 year post-stroke disabilities, limitations of activities, participation and quality of life, was carried out by telephone interview and by mail in a sample of stroke patients who returned home after having been initially managed in a stroke unit.Results: A total of 161 patients were included (142 able to answer the interview on their own; 19 needing a care-giver). Amongst a sub-group of the patients interviewed, 55.4% (95% Confidence Interval [47.1-63.7]) complained about pain and 60.0% (95% CI [51.4-68.6]) complained of fatigue; about 25% presented neuropsychological or neuropsychiatric disability. Whilst 87.3% (95% CI [81.7-92.9]) were independent for daily life activities, participation in every domains and quality of life scores, mainly in daily activity, pain, and anxiety subscales, were low.Conclusion: Despite a good 1-year post-stroke functional outcome, non-motor disabling symptoms are frequent amongst patients returned home and able to be interviewed, contributing to a low level of participation and a poor quality of life. Rehabilitation strategies focused on participation should be developed to break the vicious circle of social isolation and improve quality of life

Distribution of seafloor litter and its interaction with benthic organisms in deep waters of the Ligurian Sea (Northwestern Mediterranean)

The Mediterranean Sea is one of the most polluted marine basins and currently serves as a hotspot for marine litter. The seafloor represents the ultimate sink for most litter worldwide. Nevertheless, the knowledge about litter distribution and its interactions with benthic organisms in deep water is poorly understood. In 2018, we investigated spatial patterns of macro- and micro-litter distribution, and their effects on benthic communities in the Ligurian Sea. An oceanographic survey was carried out with a remotely operated vehicle and a multibeam echosounder on seven seamounts and canyons, at depths ranging from 350 to 2200 m. High litter accumulations were discovered at the mouth of the Monaco canyon, where estimated densities of up to 3.8 × 104 items km-2 were found at 2200 m depth. The highest abundance of urban litter items was found on the soft substrate, at the bottom of the deeper parts of the submarine canyons, which seem to act as conduits carrying litter from the shelf towards deeper areas. In contrast, fishing-related items were most abundant in the upper layer of the seamounts (300–600 m depths). Furthermore, more than 10% of the observed deep gorgonian colonies were entangled by lost longlines, indicating the detrimental effects of this fishing gear on benthic habitats. The discovery of new litter hotspots and the evaluation of how deep-sea species interact with litter contribute to increasing the knowledge about litter distribution and its effects on the deep ecosystem of the Mediterranean basin. All the observations recorded in this study showed substantial and irreversible changes in the deep and remote areas of marine environments, and these changes were found to be caused by humans. Our findings further stress the need for urgent and specific measures for the management of deep-sea pollution and the reduction of litter inputs in the environment