Long-term outcomes of paediatric Guillain-Barré syndrome.

AIM: To study long-term sequelae in children with Guillain-Barré syndrome (GBS). METHOD: This was a prospective observational study with children from two French tertiary centres. Data were from clinical and several standardized scales or questionnaires. RESULTS: Fifty-one patients were included with a median follow-up of 6 years 4 months (range 3-20 years) after the acute phase. The sequelae rate was 67% (95% confidence interval [CI] 53-78) and did not vary with time. Most children had minor sequelae (Guillain-Barré Syndrome Disability Score [GBSDS] = 1); only one was unable to run (GBSDS = 2). The most frequent complaints were paraesthesia (43%), pain (35%), and fatigue (31%). The neurological examination was abnormal in 18% of children, autonomy was compromised in 14%, and symptoms of depression occurred in 34%. The factors associated with late-onset sequelae were correlated with severity during the initial phase (i.e. initial GBSDS >4, odds ratio 6.6, 95% CI 1.8-33; p = 0.009). The predictive factors of more severe late-onset conditions were initial severity (p = 0.002) and sex (female patients; p = 0.01). INTERPRETATION: Two-thirds of children with GBS had late-onset sequelae following an episode, often minor, but sometimes with continuing effects on their everyday lives. Particularly affected were those who had severe GBS during the acute phase and who lost the ability to walk. WHAT THIS PAPER ADDS: Two-thirds of children with Guillain-Barré syndrome (GBS) had persistent sequelae. Sequelae were often minor, but daily repercussions of them were sometimes serious. Sequelae were significantly associated with severe GBS during the acute phase.

Efficacy and Safety of Eculizumab in Pediatric Patients Affected by Shiga Toxin-Related Hemolytic and Uremic Syndrome: A Randomized, Placebo-Controlled Trial.

SIGNIFICANCE STATEMENT: Shiga toxin-related hemolytic uremic syndrome (STEC-HUS) is a serious condition, characterized by multiorgan thrombotic microangiopathy, mainly affecting children. Renal involvement is severe, with approximately half of patients requiring dialysis. So far, no specific treatment has been proven efficient in STEC-HUS. The use of eculizumab, a monoclonal antibody inhibiting terminal complement complex, has demonstrated remarkable success in atypical hemolytic uremic syndrome, but its use in uncontrolled studies to treat STEC-HUS has yielded inconsistent results. In this Phase 3 randomized, placebo-controlled trial in 100 pediatric patients with STEC-HUS, the findings did not show efficacy of eculizumab during the acute phase of the disease. However, the results indicated a reduction of renal sequelae in eculizumab-treated patients at 1-year follow-up. Larger prospective studies would be needed to further explore eculizumab as a potential treatment. BACKGROUND: Shiga toxin-related hemolytic uremic syndrome (STEC-HUS) in children is a severe condition, resulting in approximately 50% of patients requiring RRT. Furthermore, at least 30% of survivors experience kidney sequelae. Recently, activation of the complement alternative pathway has been postulated as a factor in STEC-HUS pathophysiology, leading to compassionate use of eculizumab, a monoclonal antibody inhibiting the terminal complement complex, in affected patients. Given the lack of therapy for STEC-HUS, a controlled study of eculizumab efficacy in treating this condition is a priority. METHODS: We conducted a Phase 3 randomized trial of eculizumab in children with STEC-HUS. Patients were randomly assigned in a 1:1 ratio to receive either eculizumab or placebo during 4 weeks. Follow-up lasted for 1 year. The primary end point was RRT duration <48 hours after randomization. Secondary endpoints included hematologic and extrarenal involvement. RESULTS: Baseline characteristics were similar among the 100 patients who underwent randomization. The rate of RRT <48 hours did not differ significantly between the two groups (48% in the placebo versus 38% in the eculizumab group; P = 0.31) or in the course of ARF. The two groups also exhibited similar hematologic evolution and extrarenal manifestations of STEC-HUS. The proportion of patients experiencing renal sequelae at 1 year was lower in the eculizumab group than in the placebo group (43.48% and 64.44%, respectively, P = 0.04). No safety concern was reported. CONCLUSIONS: In pediatric patients with STEC-HUS, eculizumab treatment does not appear to be associated with improved renal outcome during acute phase of the disease but may reduce long-term kidney sequelae. CLINICAL TRIALS REGISTRATIONS: EUDRACT (2014-001169-28) ClinicalTrials.gov ( NCT02205541 ).

Explaining biological differences between men and women by gendered mechanisms.

BACKGROUND: The principal aim of this study was to explore if biological differences between men and women can be explained by gendered mechanisms. METHODS: We used data from the 1958 National Child Development Study, including all the living subjects of the cohort at the outcome collection wave (44-45 years). We explored several biomarkers as outcomes: systolic blood pressure, triglycerides, LDL cholesterol, HbA1c, CRP, and cortisol. Three conceptualizations of gender have been used to define methodological strategies: (a) Gender as an individual characteristic; (b) Gender as an effect of sex on socio-behavioural characteristics; (c) Gender as an interaction between sex and the social environment, here the early-life social environment. We estimated the total effect of sex and the proportion of total effect of sex at birth eliminated by gender, measured by 3 different ways according to these 3 concepts, using g-computation. RESULTS: The average level of each biomarker was significantly different according to sex at birth, higher in men for cardiometabolic biomarkers and higher in women for inflammatory and neuroendocrine biomarkers. The sizes of the differences were always smaller than one standard deviation but were larger than differences due to early-life deprivation, except for CRP. We observed gender mechanisms underlying these differences between men and women, even if the mediation effects were rarely statistically significant. These mechanisms were of three kinds: (1) mediation by socio-behavioural characteristics; (2) attenuation by gendered mechanisms; (3) interaction with early social environment. Indeed, we observed that being born into a deprived rather than non-deprived family increased metabolic and inflammatory biomarkers levels more strongly in females than in males. CONCLUSIONS: The biological differences between men and women seem to not be purely explained by biological mechanisms. The exploration of gender mechanisms opens new perspectives, in terms of methodology, understanding and potential applications.

Toward a conceptual framework of health and its operational definition: an application in the 1958 British birth cohort.

BACKGROUND: Defining and measuring Health presents a challenge, partly due to its conceptual pluralism. To measure Health as an ability to adapt and self-manage, we developed an approach within the theoretical framework of resources and reserves over the life course, recently proposed in the literature. We aimed to (i) use the conceptual framework developed to identify indicators of deteriorating health reserves, (ii) construct an overall health measure from these indicators, (iii) evaluate the association between the overall health measure and subsequent health outcomes and (iv) assess the robustness of our method. METHODS: We used data from 7,043 individuals born in 1958 in Great Britain included in the National Child Development Study. An overall health measure was constructed via the sum of three selected indicators of deteriorating health reserves in mid-life: chronic widespread pain (CWP), Clinical Interview Schedule - revised (CIS-r), and allostatic load (AL). A three-category variable was defined: impaired/medium/optimal overall health. We explored criterion validity by modelling the relationships between the overall health measure, or each reserve taken separately at 44-45 years, and self-rated health at 46 years and mortality up to 58 years, corresponding to 14 years of follow up, using Cox and logistic regressions respectively. We performed comparative analyses to assess the robustness of the method. RESULTS: Having an impaired overall health measure was significantly associated with all-cause premature mortality (HRimpaired = 2.74 [1.86; 4.05]) and an increased risk of later fair/poor/very poor self-rated health (ORimpaired = 7.50 [6.29; 8.95]). The overall health measure had a greater effect on the self-rated health estimates than each indicator of deteriorating health reserves considered separately (ORAL medium = 1.82 [1.59; 2.09]; ORAL high = 2.74 [2.37; 3.16]; ORCIS-r = 5.20 [4.45; 6.08]; ORCWP = 2.85 [2.53; 3.21]). CIS-r and allostatic load were also associated with premature mortality contrary to chronic widespread pain (HRAL medium1.82 [1.27; 2.61]; HRAL high = 3.10 [2.19; 4.40]; HRCIS-r = 1.77 [1.22; 2.56]; HRCWP = 1.32 [0.98; 1.76]). The multiple comparative analyses conducted allowed us to assess the robustness of our method within this cohort. CONCLUSIONS: We proposed a method for measuring Health in mid-life in line with the concept of Health as the ability to adapt and self-manage and the concept of health reserves. This method may be applied and further developed within the field of social and positive epidemiology.

A national population-based study of patients, bystanders and contextual factors associated with resuscitation in witnessed cardiac arrest: insight from the french RéAC registry.

BACKGROUND: In out-of-hospital cardiac arrest (OHCA), bystander initiated cardiopulmonary resuscitation (CPR) increases the chance of return of spontaneous circulation and survival with a favourable neurological status. Socioeconomic disparities have been highlighted in OHCA field. In areas with the lowest average socioeconomic status, OHCA incidence increased, and bystander CPR decreased. Evaluations were performed on restricted geographical area, and European evaluation is lacking. We aimed to analyse, at a national level, the impact of area-level social deprivation on the initiation of CPR in case of a witnessed OHCA. METHODS: We included all witnessed OHCA cases with age over 18 years from July 2011 to July 2018 form the OHCA French national registry. We excluded OHCA occurred in front of rescue teams or in nursing home, and patients with incomplete address or partial geocoding. We collected data from context, bystander and patient. The area-level social deprivation was estimated by the French version of the European Deprivation Index (in quintile) associated with the place where OHCA occurred. We assessed the associations between Utstein variables and social deprivation level using a mixed-effect logit model with bystander-initiated CPR. RESULTS: We included 23,979 witnessed OHCA of which 12,299 (51%) had a bystander-initiated CPR. More than one third of the OHCA (8,326 (35%)) occurred in an area from the highest quintile of social deprivation. The higher the area-level deprivation, the less the proportion of bystander-initiated CPR (56% in Quintile 1 versus 48% in Quintile 5). The In the multivariable analysis, bystander less often began CPR in areas with the highest deprivation level, compared to those with the lowest deprivation level (OR=0.69, IC95%: 0.63-0.75). CONCLUSIONS: The level of social deprivation of the area where OHCA occurred was associated with bystander-initiated CPR. It decreased in the more deprived areas although these areas also concentrate more younger patients.

The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk.

BACKGROUND: Women with an advantaged socioeconomic position (SEP) have a higher risk of developing breast cancer (BC). The reasons for this association do not seem to be limited to reproductive factors and remain to be understood. We aimed to investigate the impact of lifecourse SEP from childhood and social mobility on the risk of BC considering a broad set of potential mediators. METHODS: We used a discovery-replication strategy in two European prospective cohorts, E3N (N = 83,436) and EPIC-Italy (N = 20,530). In E3N, 7877 women were diagnosed with BC during a median 24.4 years of follow-up, while in EPIC-Italy, 893 BC cases were diagnosed within 15.1 years. Hazard ratios (HR) were estimated using Cox proportional hazard models on imputed data. RESULTS: In E3N, women with higher education had a higher risk of BC (HR [95%CI] = 1.21 [1.12, 1.30]). This association was attenuated by adjusting for reproductive factors, in particular age at first childbirth (HR[95%CI] = 1.13 [1.04, 1.22]). Health behaviours, anthropometric variables, and BC screening had a weaker effect on the association. Women who remained in a stable advantaged SEP had a higher risk of BC (HR [95%CI] = 1.24 [1.07; 1.43]) attenuated after adjustment for potential mediators (HR [95%CI] = 1.13 [0.98; 1.31]). These results were replicated in EPIC-Italy. CONCLUSIONS: These results confirm the important role of reproductive factors in the social gradient in BC risk, which does not appear to be fully explained by the large set of potential mediators, including cancer screening, suggesting that further research is needed to identify additional mechanisms.

How a personalised transportable folding device for seating impacts dysphagia.

PURPOSE: A personalised transportable folding device for seating (DATP) on a standard seat was developed by an occupational therapist at the Toulouse University Hospital Centre (patent no. WO 2011121249 A1) based on the hypothesis that the use of a seat to assist with better positioning on any chair during meals modifies the sitting posture and has an impact on cervical statics which increases the amplitude of movements of the axial skeleton (larynx and hyoid bone) and benefits swallowing. The aim of this work is to demonstrate that an improvement in sitting posture with the help of the DATP, through Hyoid bone motion, has an impact on the quality of swallowing in a dysphagic population which benefits from the device in comparison to a dysphagic population which does not benefit from the device after 1 month of care. The secondary endpoints concern the evaluation of the impact on other characteristics of swallowing, posture, the acceptability of the device and the quality of life. METHODOLOGY: This is a randomised comparative clinical trial. The blind was not possible for the patients but the examiner who evaluated the outcome criterion was blinded to the group to which the patient belonged. The outcome criterion was the measurement of the hyoid bone movement during swallowing. The other criteria were collected during the videofluoroscopic examination of swallowing and by use of a questionnaire. Fifty-six (56) patients were included: 30 in the group without device (D-) and 26 in the group with the device (D+). All the patients benefited from a training course on seating. Only the D+ patients participated in this course where the use of the device was explained and the device was then kept for use at home for 1 month. RESULTS: A significant improvement was noted in the postural criteria before and after use, in favour of a better posture for the two groups (p < 0.001) and more hyoid bone motion in the D+ group. The difference was significant in the bivariate analysis for horizontal movement (p = 0.04). After adjustment of potential factors of confusion, we noted a significant mean difference for the three distances in the D+ group in comparison to the D- group, of + 0.33 (95% CI [+ 0.17; + 0.48]) for horizontal movement, + 0.22 (95% CI [+ 0.03; + 0.40]) for vertical movement and + 0.37 (95% CI = [+ 0.20; + 0.53]) for horizontal movement. However, the other parameters, and notably the other swallowing markers were not significantly modified by the use of the device. CONCLUSION: The personalised transportable folding device for seating developed to reduce dysphagia has an action on hyoid bone motion during swallowing. However, this positive effect on an intermediate outcome criterion of the quality of swallowing was not associated with an improvement in swallowing efficiency in the study population. The diversity of diseases with which the patients in this study were afflicted is a factor to be controlled in future studies with this device.

Why are people increasingly attending the emergency department? A study of the French healthcare system.

OBJECTIVE: It is often asserted that the crowding phenomenon in emergency departments (ED) can be explained by an increase in visits considered as non-urgent. The aim of our study was to quantify the increase in ED visit rates and to determine whether this increase was explained by non-severe visit types. METHODS: This observational study covers all ED visits between 2002 and 2015 by adult inhabitants of the Midi-Pyrénées region in France. Their characteristics were collected from the emergency visit summaries. We modelled the visit rates per year using linear regression models, and an increase was considered significant when the 95% CIs did not include zero. The severity of the patients' condition during ED visit was determined through the 'Clinical Classification of Emergency' score. Non-severe visits were those where the patient was stable, and the physician deemed no intervention necessary. Intermediate-severity visits concerned patients who were stable but requiring diagnostic or therapeutic procedures. RESULTS: The 37 studied EDs managed >7 million visits between 2002 and 2015. There was an average increase of +4.83 (95% CI 4.33 to 5.32) visits per 1000 inhabitants each year. The increase in non-severe visit types was +0.88 (95% CI 0.42 to 1.34) per 1000 inhabitants, while the increase in intermediate-severity visit types was +3.26 (95% CI 2.62 to 3.91) per 1000 inhabitants. This increase affected all age groups and all sexes. DISCUSSION: It appears that the increase in ED use is not based on an increase in non-severe visit types, with a greater impact of intermediate-severity visit types requiring diagnostic or therapeutic procedures in ED.

Characteristics of Lung Cancer in Patients Younger than 40 Years: A Prospective Multicenter Analysis in France.

OBJECTIVES: The aim of this study was to describe the demographic and clinico-pathological characteristics of lung cancer in patients younger than 40 years. MATERIALS AND METHODS: This was a prospective study performed within the Groupe Français de Pneumo-Cancérologie. Consecutive patients diagnosed with lung cancer before the age of 40 years were eligible. Data on demographics, medical history, clinico-pathological characteristics, treatment and overall survival were analysed. RESULTS: In total, 146 patients were included from January 2011 to December 2013. Median age was 38 years (IQR: 34-40). Women accounted for 41%. Main histological type was adenocarcinoma (77%). Only 3% had a prior history of cancer, but a family history (first- or second-degree relatives) of cancer was reported in 80 (55%) patients; 85 and 50% were current or past smokers of tobacco and cannabis, respectively; 82% had stage IIIB/IV at diagnosis. Median overall survival was 15.3 (95% CI: 8.1-24.0) months in the whole population, 10.3 (95% CI: 12.5-14.2) months in stage IV and 15 (95% CI: 8.7-35.2) months in stage III. One- and two-year overall survival rates were 57% (95 CI: 49-65) and 31.5% (95 CI: 27-43), respectively. Compared to smokers, non-smokers were significantly younger and more often females. Median overall survival was not statistically different between smokers and non-smokers.

Validation of the cutaneous impact location to predict intracranial lesion among elderly admitted to the Emergency Department after a ground-level fall.

INTRODUCTION: In the Emergency Departments, almost one out of two head CT scans are carried out for traumatic brain injuries among elderly victims of ground level-falls. Recently, a new predictive factor for intracranial lesions in this population has been suggested: presence and location of cutaneous impact. The aim of this study was to establish determinants of intracranial lesion among older patients admitted to EDs due to ground-level falls with traumatic brain injury using the head cutaneous impact location. METHODS: A retrospective, observational and monocentric study of patients admitted to Emergency Department for ground-level falls with traumatic brain injury was carried out between 01 January 2017 and 31 July 2017. The primary outcome was identification of an acute intracranial lesion. A bootstrap procedure was employed to evaluate performance and internal validity of the final model. RESULTS: Among the 1036 patients included, the mean age was 85.6 (SD 7.6) years and 94/1036 (9.1%, 95% CI 7.4-10.9) patients presented with an acute intracranial lesion. Multivariable analysis adjusted by bootstrap shrinkage showed that compared with temporal-parietal or occipital impact, Odds Ratio of intracranial lesions were 0.61 (95% CI 0.39-0.95, p = 0.03) in patients with frontal impact, 0.27 (95% CI 0.12-0.59, p = 0.001) in patients with facial impact and 0.21 (95% CI 0.06-0.77, p = 0.018) in patients without cutaneous impact. Subcutaneous hematoma (OR 1.97, p = 0.007), loss of consciousness (OR 4.66, p<0.001), fall-related amnesia (OR 2.58, p = 2.6), vomiting (OR 2.62, p = 0.002) and altered Glasgow Score (OR 6.79, p<0.001) were as well associated with high risk of intracranial lesion. Taking antiplatelets or anticoagulants were not associated with an increased risk of intracranial lesions. The model discrimination was adequate (C-statistic 0.79; 95% CI 0.73 - 0.85). CONCLUSION: Our results establish specific determinants of intracranial lesions among elderly after ground level-falls. The cutaneous impact location may identify patients with high risk of intracranial lesion. Further researches are needed to propose a specific score based on these determinants so as to better target Head CT scan use.