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Objectives: The aim of the study was to measure the economic impact of informal care (IC) on caregivers assisting myocardial infarction (MI) survivors in France. Health and social impacts were also described., Methods: Data from the prospective 2008 Health and Disabilities Households Survey (Enquête Handicap-Santé), carried out among the French general population, were used to obtain information about patients with MI and their informal caregivers. To estimate the approximate monetary value of IC, three methods were used: the proxy good method, opportunity cost method (OCM), and contingent valuation method (CVM). A multivariate analysis was performed to determine the associations of the IC duration and the existence of professional care with the health indicators stated by caregivers., Results: The analysis included data from 147 caregivers. The mean value of IC ranged from €9,679 per year using the CVM to €11,288 per year using the OCM (p > .05). The mean willingness to pay for an additional hour of IC was €10.9 (SD = 8.3). A total of 46.2 percent of caregivers reported that IC negatively affected theirs physical condition, and 46.3 percent reported that it negatively affected their psychological health. In addition, 40.1 percent declared that caregiving activity made them anxious and 38.8 percent stated they felt alone. Associations were identified between the duration of IC and feeling the need to be replaced, feeling alone and making sacrifices (p < .05)., Conclusions: Informal caregiver burden may be recognized in health technology assessment in order not to underestimate the cost of strategies and to facilitate the comparability of cost-effectiveness outcomes between studies.

Osteoporosis (OP) is responsible for an important economic burden, but OP care is far from meeting therapeutic guidelines. Some interventions were effective to improve OP management. Our objective was to evaluate the cost-effectiveness of these interventions. Structural interventions and interventions consisting in sending educational material were dominant strategies., Purpose: Osteoporosis (OP) causes many osteoporotic fractures worldwide and an important economic burden as a result. OP care is far from meeting treatment guidelines, but in a recent meta-analysis, we showed that some interventions were effective to improve appropriate bone mineral density (BMD) and treatment prescriptions. In the context of limited resources, it is of major importance to measure these interventions' efficiency. Our objective was to evaluate the cost-effectiveness of existing effective intervention types., Methods: We used a decision tree incorporating Markov models to compare costs and benefits (quality-adjusted life-years or QALYs) between usual care and three intervention types: structural (I), direct educational through conversation (II), and indirect educational by sending material (III). We adopted the collectivity perspective and chose a 30-year time horizon. The model included efficacy of interventions and risk of further fracture or death, depending on BMD T-score results and OP management, obtained from published literature. The model was populated to reflect a French setting. Deterministic and probabilistic sensitivity analyses were conducted. Costs were presented in 2018 euros (€)., Results: Interventions type I and III were dominant strategies compared with usual care (cost-saving with a QALY gain). Our results were consistent through sensitivity analyses., Conclusion: Our results suggest that structural interventions and indirect interventions to improve OP care (BMD and OP treatment prescription), in women 50 years old with a first fragility fracture, were dominant strategies.

Background: In patients with suspected stroke, brain imaging is recommended in the acute phase for appropriate management and treatment. Both computed tomography (CT) and magnetic resonance imaging (MRI) are considered reasonable choices for initial brain imaging. When both techniques are available, choosing one or the other might be associated with specific factors related either to patients, stroke symptoms, and severity or management organization., Methods: The study was performed within the STROKE 69 database, a population-based cohort of all adult patients with suspected stroke admitted in one of the emergency departments (ED), primary stroke center, or stroke center of the Rhône County, from November 2015 to December 2016. Patients were included if they were admitted within 24 h following either symptom onset or last known normal. To identify factors potentially associated with the choice of initial brain imaging, a multivariate logistic regression was performed., Results: Among the 3,244 patients with suspected stroke enrolled in the STROKE69 cohort, 3,107 (95.8%) underwent brain imaging within the first 24 h after admission. Among those 74.6% underwent CT as initial imaging while 25.4% had an MRI. In multivariate analyses, several factors were associated with a lower probability of having an MRI as initial brain imaging versus CT. These were either patient characteristics: older age (>80 years old, OR 0.39 [95% CI 0.28-0.54]), preexisting disability (OR 0.55 [95% CI 0.36-0.84]), use of anticoagulants (OR 0.52 [95% CI 0.33-0.81]), stroke characteristics: stroke of unknown onset (OR 0.42 [95% CI 0.31-0.58]) or factors associated with overall management: onset-to-door time (>6 h, OR 0.38 [95% CI 0.23-0.60]), initial admission to ED (OR 0.02 [95% CI 0.02-0.04]) or intensive care unit (OR 0.01 [95% CI 0.001-0.08]), personal transport (OR 0.66 [95% CI 0.45-0.96]), and admission during working hours (OR 0.65 [95% CI 0.51-0.84])., Conclusions: Besides CT or MRI availability, a number of other parameters could influence the choice of first imaging in case of stroke suspicion. These are related to patient characteristics, type of stroke symptoms, and type of organization., (© 2020 S. Karger AG, Basel.)

Background  Endoscopic mucosal resection (EMR) with snare is the recommended technique to resect non-invasive colorectal neoplastic lesions between 10 and 30 mm in diameter. The objective of EMR is to resect completely the neoplastic tissue en bloc and preferably with free margins (R0), avoiding recurrences. Anchoring the tip of the snare in the submucosa is a technical trick that allows snare sliding to be reduced and larger pieces to be caught. The aim of the present study was to evaluate the effectiveness and safety of anchoring-EMR (A-EMR). Methods  This was a retrospective analysis of A-EMR procedures for lesions of diameter between 10 and 30 mm (endoscopic evaluation) performed consecutively in four French centers between May 2017 and January 2018. A-EMR was routinely performed for all EMR using Olympus conventional snares (10 or 25 mm). The primary outcome was evaluation of the proportion of R0 resections. Results  A total of 141 A-EMR procedures were performed by 10 operators. Mean lesion size was 19.8 mm. Anchoring was feasible in 96.5 % of cases. There were 81.6 % en bloc resections and 70.2 % R0 resections, with the percentage of procedures decreasing with increasing lesion size (82.8 % < 20 mm, 55.3 % 21 - 30 mm, and 50.0 % > 30 mm, P  = 0.002). Complete perforations closed endoscopically occurred in 3/141 cases (2.1 %); none occurred in lesions < 20 mm in size (0 /87). Conclusion  The A-EMR technique appears to be promising with a high proportion of R0 for lesions of 10 - 20 mm in size without any perforations. It could also offer an alternative to endoscopic submucosal dissection (ESD), or to hybrid techniques to reach R0 for lesions between 20 and 30 mm in size.

Objectives: Our objective was to compare the cardiovascular safety of tocilizumab and other biological disease-modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis using a network meta-analysis (NMA)., Methods: A systematic literature search through May 2018 identified randomized controlled trials (RCT) or observational studies (cohort only) reporting cardiovascular outcomes of tocilizumab (TCZ) and/or abatacept (ABA) and/or rituximab (RTX) and/or tumor necrosis factor inhibitors (TNFi) in rheumatoid arthritis patients. The composite primary outcome was the rate of major adverse cardiovascular outcomes (MACE, myocardial infarction (MI), peripheral artery disease (PAD) and cardiac heart failure (CHF))., Results: 19 studies were included in the NMA, including 11 RCTs and 8 cohort studies. We found less events with RTX (5.41 [1.70;17.26]. We found no difference between TCZ and other treatments. Concerning MI, we found no difference between TCZ and csDMARD (4.23 [0.22;80.64]), no difference between TCZ and TNFi (2.00 [0.18;21.84]). There was no difference between TCZ and csDMARD (1.51[0.02;103.50] and between TCZ and TNFi (1.00 [0.06;15.85]) for stroke event. With cohorts and RCT NMA, we found no difference between TCZ and other treatments for MACE (0.66 [0.42;1.03] with ABA, 1.04 [0.60;1.81] with RTX, 0.78[0.53;1.16] and 0.91 [0.54;1.51] with csDMARD), but the risk of myocardial infarction was lower with TCZ compared to ABA (0.67 [0.47;0.97]). We lacked data to compare TCZ and other bDMARD for stoke and MI. Not enough data was available to perform a NMA for CHF and PAD., Conclusions: Despite an increase in cholesterol levels, TCZ has safe cardiovascular outcomes compared to other bDMARD., Competing Interests: The authors have declared that no competing interests exist.

Background: Traumatic exposure is a frequent issue in patients visiting emergency departments (EDs). Some patients will subsequently develop post-traumatic stress disorder (PTSD) while other will not. The problem is under-diagnosed in EDs and no standardized management is provided to prevent PTSD. Most studies focused on a particular group of trauma whereas we need a global approach to further develop interventions for detecting and treating patients at high risk. We aim to assess the prevalence of traumatic exposure and situation at high risk of further PTSD and identify pre and peri-traumatic biopsychosocial factors predisposing individuals to PTSD in the general context of EDs., Methods: This comprehensive multicenter study will have two steps. The first step will be a cross-sectional study on moderate and high risk of PTSD prevalence among EDs visitors with a recent history of trauma. All patients aged 18-70 years, presenting with a recent history of trauma (< 1 month) in one of the six EDs in the Auvergne-Rhône-Alpes region (≈1/10° of the French population) will be included over a 1-month period and approximately 1500 subjects are expected in this cross-sectional step. The risk of PTSD will be assessed using the Impact of Event Scale Revised (IES-R). Self-administered questionnaires will be used to measure acute stress (IES-R), and a number of potential bio-psycho-social risk factors. Demographic and physical health-related data will be collected from medical file. Second step will be a prospective cohort study within a sub-sample of 400 patients enrolled in step 1, randomly selected with stratification on sex, age, ED, and IES-R score. At 3 months, PTSD will be defined by a ≥ 33 score at PTSD Check List for DSM-5 (PCL-5) through a telephone interview. We will evaluate definite PTSD biopsychosocial predictive factors using a multivariate logistic regression model and describe evolution of PTSD at 3 months., Discussion: This is the first study to assess PTSD predictors prospectively with a biopsychosocial approach within a cohort representative of EDs visitors. The results will inform the development of dedicated interventions to decrease the risk of subsequent PTSD., Trial Registration: ClinicalTrials.gov: NCT03615014 ; ISSUE protocol 2nd version was approved on 07/08/2018.

Background: Our objective was to review economic evaluations on stent-retriever thrombectomy (SRT) added/not added to intravenous (IV) tissue plasminogen activator (t-PA) in acute ischemic stroke (AIS) due to large-vessel occlusion (LVO)., Methods: We conducted a systematic review using several electronic databases and searching for studies published from January 2009 to September 2017., Inclusion Criteria: any publication type reporting the incremental cost-effectiveness ratio of SRT in people with AIS secondary to LVO. Quality assessment was undertaken with the CHEERS and the Philips' checklists., Results: Eight original articles (four from North America/four from Europe) were included; of these, seven were model-based cost-effectiveness studies and one was a study conducted alongside a clinical trial. The perspective was the healthcare system in seven studies, and societal in one. The time horizon was lifetime (minimum 20 years) in all but two studies where it was 1 and 5 years. Overall, studies were rated of good quality (mean score 79%; range 70-90). Data sources, effectiveness outcomes and other input parameters were heterogeneous across studies. In three studies, SRT was dominant (less expensive and more effective). In five studies, SRT was more expensive and generated more quality-adjusted life years but had a high probability (79-100%) to be cost-effective at conventional thresholds., Conclusion: This review shows that SRT added/not added to IV t-PA is likely to be cost-effective or even dominant, which is consistent with the opinion from several Health Technology Assessment bodies recommending SRT. However, our findings are supported by primary studies with substantial methodological heterogeneity.

Background: Secondary prevention is inadequate in the first 2 years after stroke but what happens after that is less documented. The aim of this study was to assess the use and the adherence to preventive drugs 3 and 6 years after experiencing a transient ischemic attack (TIA) or an ischemic stroke (IS)., Methods: The population study was from the AVC69 cohort (IS or TIA admitted in an emergency or stroke unit in the Rhône area, France, for an IS or a TIA during a 7-month period). Medication use was defined as ≥1 purchase during the studied year and adherence as Continuous Measure of Medication Acquisition ≥0.8 using the French medical insurance health care funding database., Results: The study population consisted of 210 patients at 3 years and 163 patients at 6 years. Medication use at 3 and 6 years was, respectively, 80.9 and 79.8% for antithrombotics, 69.1 and 66.3% for antihypertensives, 60.5 and 55.2% for statins and 48.6 and 46.6% for optimal treatment defined as the treatment achieved by the use of the 3 drugs. Adherence to each class was good at 3 years and tends to decrease at 6 years., Conclusions: More than one patient out of 2 do not use the optimal preventive treatment., (© 2018 S. Karger AG, Basel.)

Abstract: Selenoprotein-related myopathy ( SEPN1 -RM) is a rare disease with a variable clinical presentation. The selenoprotein N1 gene ( SEPN1 ) mutation causing this congenital muscular dystrophy was identified in 2001. Sleep-disordered breathing (SDB) may occur in young patients with SEPN1 -RM who are still able to walk. We report the cases of two children with SEPN1 -RM who presented with SDB at the ages of 7 and 12 years and for whom long-term nocturnal noninvasive ventilation yielded significant improvement. Based on literature review and our current cases, it seems that there is no obvious relationship between the time since SDB onset and outcome of pulmonary function tests or limb muscle weakness. We therefore suggest that SDB should be systematically screened for in patients with SEPN1 -RM, at regular intervals using nocturnal polysomnography., (© 2017 American Academy of Sleep Medicine)

A worldwide increase in the frequency of testing for serum 25-hydroxyvitamin D (25OHD) levels has been observed over the last years. Our aim was to measure the evolution in the number of vitamin D assays performed in France from 2008 to 2013 and to investigate some of the drivers that may explain this increase. Patients within the representative 1/97th sample of the French health insurance system reimbursement database (EGBS database) who had at least one 25OHD or 1-25(OH) 2 D assay between 2008 and 2013 were included. Trends over time in number of vitamin D assays were analysed globally and per year in a multivariable Poisson regression model with GEE. Among the 639,163 patients of the EGBS database, 118,509 (18.5%) had at least one vitamin D assay over the 6-year study period. Among the individuals tested, 52.1% had only one test. The number of vitamin D assays (25OHD or 1-25(OH) 2 D) increased 7.5-fold from 9,620 in 2008 to 81,641 in 2013. This study confirms the rapid and dramatic increase in vitamin D assays prescriptions and shows that this is mostly due to a global increase of the proportion of patients tested rather than an increase in repetition of tests in some individual patients.

High-flow nasal cannula oxygen therapy (HFNC) is a technique for noninvasive ventilation commonly used in pediatric intensive care units for respiratory distress, particularly in acute bronchiolitis. HFNC was introduced in the pediatric emergency department of the Reims university hospital for the treatment of infants with moderate to severe acute viral bronchiolitis. This retrospective observational study aimed to investigate the use of HFNC in a pediatric emergency ward, describing the groups of infants with acute viral bronchiolitis to be treated either with conventional oxygen therapy or with HFNC therapy. A total of 89 infants aged less than 6 months were included between December 2013 and April 2014. The choice of the type of oxygen used belonged to the pediatrician, according to his or her assessment of the clinical severity of the patient's condition, guided by a protocol of HFNC use for the treatment of moderate to severe bronchiolitis and limited by the availability of a single device in the department. Eighty-nine infants were included; 64% were boys. Fifty-seven infants (64%) had no medical history. At admission, 39 infants (46.4%) had tachypnea and 75 (84.3%) intercostal indrawing. RSV was found in 75 infants (97.4% of infants had a positive respiratory virology test). Seventy-six infants (85.4%) were treated with conventional oxygen therapy and 13 (14.6%) with HFNC. At admission, the mean weight for infants treated with HFNC was lower (P=0.03), the oxygen saturation level was 86.7% versus 93.5% (P=0.03) for conventional oxygen therapy. Moreover, modified Wood's score was higher and the mean PCO 2 was 61.1 versus 49.9mmHg (P<0.01). Six infants treated with conventional oxygen therapy (7.9%) and six with HFNC (46.1%) were then transferred to an intensive care unit. HFNC therapy in the pediatric emergency ward seems to be an advantageous therapeutic option in the early treatment of infants with moderate to severe bronchiolitis, but further studies are needed to specify its indications and effectiveness., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Treatment initiation rates following fragility fractures have often been reported to be low and in recent years numerous programs have been implemented worldwide to increase them. This study aimed at describing osteoporosis (OP) treatment initiation in a representative sample of women who were hospitalized for a distal forearm fracture (DFF) or proximal humerus fracture (PHF) in 2009-2011 in France. The data source was a nationwide sample of 600,000 individuals, extracted from the French National Insurance Healthcare System database. All women aged 50 years and older who were hospitalized for a DFF or PHF between 2009 and 2011 and who had not received any OP treatment in the preceding 12 months were included in a retrospective cohort study. OP treatments initiated during the year following the fracture were analyzed. From 2009 to 2011, 729 women were hospitalized for a DFF or a PHF and 284 were on OP treatment at the time of the fracture occurrence. Among the 445 women who had no prevalent OP treatment, 131 (29.4%) received supplementation treatment only (vitamin D and/or calcium) and 42 (9.4%) received a pharmacologic OP treatment in the year following their fracture. Pharmacological OP treatments included bisphosphonates (n = 21), strontium ranelate (n = 14), hormone replacement therapy (n = 4), or raloxifene (n = 3). General practitioners prescribed 75% of initial OP treatments. Despite the guidelines published in 2006 and the numerous initiatives to promote post-fracture OP treatment, OP treatment initiation rate in women who were hospitalized for a fragility fracture remained low in 2009-2011 in France.

The objective of this study was to perform genetic analysis in three brothers of Turkish origin born from consanguineus parents and affected by congenital hypothyroidism, goiter and low levels of serum TG. The combination of sequencing of DNA, PCR mapping, quantitative real-time PCR, inverse-PCR (I-PCR), multiplex PCR and bioinformatics analysis were used in order to detect TG mutations. We demonstrated that the three affected siblings are homozygous for a DNA inversion of 16,962bp in the TG gene associated with two deleted regions at both sides of the inversion limits. The inversion region includes the first 9bp of exon 48, 1015bp of intron 47, 191bp of exon 47, 1523bp of intron 46, 135bp of exon 46 and the last 14,089bp of intron 45. The proximal deletion corresponds to 27bp of TG intron 45, while the distal deletion spans the last 230bp of TG exon 48 and the first 588bp of intergenic region downstream TG end. The parents were heterozygous carriers of the complex rearrangement. In conclusion, a novel large imperfect DNA inversion within the TG gene was identified by the strategy of I-PCR. This aberration was not detectable by normal sequencing of the exons and exon/intron boundaries. Remarkably, the finding represents the first description of a TG deficiency disease caused by a DNA inversion., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Clinical presentation of sarcoidosis in children is very variable and dependant upon age. Herein, we report the first association of massive splenomegaly and pancytopenia as the revealing mode of sarcoidosis in an 8-year-old girl who, despite bone marrow involvement, had a remarkable good outcome following steroid therapy.

Background: Open-heart surgery can result in adhesions, which can complicate resternotomy., Aims: To document the occurrence of adhesions after the use of a new collagen membrane; to evaluate its tolerability; and to compare surgical parameters with control patients., Methods: Paediatric patients who underwent cardiac surgery with the collagen membrane (Cova™ CARD; Biom'up, Saint Priest, France) were analysed retrospectively for levels of adhesion and tolerability. The times of dissection and intervention and the transfusion of packed red blood cells and haemostatic products were compared to a historic cohort who did not receive an anti-adhesion device., Results: From January 2010 to December 2011, 36 patients received a collagen membrane. Nineteen re-interventions were performed, after a mean of 169 days. No grade 3 adhesions were observed and no tolerability problems were reported. During re-interventions after more than 30 days, the propensity score-adjusted durations of dissection and the total process for patients with and without a collagen membrane were 32 vs 41 minutes and 151 vs 182 minutes, respectively (not significant). The mean quantities of red blood cells and biological glue administered in the two groups were 98 vs 139 mL and 1.2 vs 0.5 mL, respectively (not significant)., Conclusions: This feasibility study shows the potential use of the new membrane in paediatric patients, both in terms of prevention from severe adherence and tolerability. This is the first study of this membrane in humans. A prospective, controlled study is necessary to provide strong evidence of its efficiency., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Aim: Whether or not voiding cystourethrography (VCUG) should be performed after a first episode of urinary tract infection (UTI) remains a matter of debate. The role of VCUG is primarily to diagnose high-grade vesicoureteral reflux (≥grade III) (VUR) and hence prevent the development of renal scars and poor long-term outcome. We designed a protocol designed to reduce the indications for performing unnecessary VCUGs after a first episode of febrile UTI. In order to evaluate the efficacy of our protocol, we designed a retrospective study to verify whether high-grade VUR was subsequently being underdiagnosed., Methods: This study compared the number of cases of VUR diagnosed over 2 1-year periods in children aged 1 month to 18 years. Data were collected from records held in the pediatric emergency department of the University Hospital of Reims. All cases included had presented to the department with a first episode of febrile UTI. During the first 1-year collection period, all patients underwent a VCUG. During the second collection period, the protocol was in place and VCUG was only performed in children with a serum procalcitonin level greater than 1 ng/L and/or an abnormal renal ultrasound scan., Results: During the first year, 100 patients underwent routine VCUG and 7 cases of high-grade VUR were diagnosed. During the following year, VCUG was limited according to the new protocol: 102 patients were enrolled, 52 VCUGs were performed and 8 cases of high-grade VUR were diagnosed. Cases of low-grade VUR (I and II) were less frequently detected, without significant consequences for the patients., Conclusion: The protocol led to a 40% decrease in the number of VCUGs performed. No cases of high-grade VUR were missed; however, the number of VCUGs performed with a normal outcome remained significant., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Small cells dominate photosynthetic biomass and primary production in many marine ecosystems. Traditionally, picoplankton refers to cells < or =2 microm. Here we extend the size range of the organisms considered to 3 microm, a threshold often used operationally in field studies. While the prokaryotic component of picophytoplankton is dominated by two genera, Prochlorococcus and Synechococcus, the eukaryotic fraction is much more diverse. Since the discovery of the ubiquitous Micromonas pusilla in the early 1950s, just over 70 species that can be <3 microm have been described. In fact, most algal classes contain such species. Less than a decade ago, culture-independent approaches (in particular, cloning and sequencing, denaturing gradient gel electrophoresis, FISH) have demonstrated that the diversity of eukaryotic picoplankton is much more extensive than could be assumed from described taxa alone. These approaches revealed the importance of certain classes such as the Prasinophyceae but also unearthed novel divisions such as the recently described picobiliphytes. In the last couple of years, the first genomes of photosynthetic picoplankton have become available, providing key information on their physiological capabilities. In this paper, we discuss the range of methods that can be used to assess small phytoplankton diversity, present the species described to date, review the existing molecular data obtained on field populations, and end up by looking at the promises offered by genomics.

The genetic diversity of picoplanktonic (i.e. cells that can pass through a 3 mum pore-size filter) green algae was investigated in the Mediterranean Sea in late summer by a culture-independent approach. Genetic libraries of the 18S rRNA gene were constructed using two different primer sets. The first set is commonly used to amplify the majority of eukaryotic lineages, while the second was composed of a general eukaryotic forward primer and a reverse primer biased towards the phylum Chloroplastida. A total of 3980 partial environmental sequences were obtained: 1668 using the general eukaryotic primer set and 2312 using the Chloroplastida-biased primer set. Of these sequences, 65 (4%) and 594 (26%) belonged to the Chloroplastida respectively. A 99.5% sequence similarity cut-off value allowed classification of these 659 Chloroplastida sequences into 74 different operational taxonomic units. A majority of the Chloroplastida sequences (99%) belonged to the prasinophytes. In addition to the seven independent prasinophyte lineages previously described, we discovered two new clades (clades VIII and IX), as well as a significant genetic diversity at the species and subspecies levels, notably among the genera Crustomastix, Dolichomastix and Mamiella (Mamiellales), but also within Pyramimonas and Halosphaera (Pyramimonadales). Such diversity within prasinophytes has not previously been observed by cloning approaches, illustrating the power of using targeted primers for clone library construction. Prasinophyte assemblages differed especially in relation to nutrient levels. Micromonas and Ostreococcus were mainly recovered from mesotrophic areas, whereas Mamiella, Crustomastix and Dolichomastix were mostly detected in oligotrophic surface waters. Within genera such as Ostreococcus or Crustomastix for which several clades were observed, depth seemed to be the main factor controlling differential distribution of genotypes.