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Purpose The aim of this study was to explore the beliefs, perceptions and representations of patients in order to identify the determinants of oral anticancer drugs adherence and to take action in current practice to improve patient support in digestive oncology. Methods We constructed a semi-directed interview guide which aimed to explore the patient’s relationship with medication, their health history, their experiences at the time of the announcement of treatment, their confidence, their fears, their motivations to adhere to their treatment and the constraints linked to their treatment. The data were analysed and discussed using a thematic approach. Results Seventeen patients agreed to participate in the study. The median age was 60 years. Ten patients had colorectal cancer, 3 patients had hepatocellular carcinoma, 3 patients had gastrointestinal stromal tumour and 1 patient had neuroendocrine pancreatic tumour. We identified five categories of factors influencing adherence: demographic and socioeconomic, disease-related, treatment-related, care system-related, and patient representation and pathways’ factors. A majority of patients emphasised the importance of family support in the adherence process and the convenience of per os treatment compared to other intravenous treatments. However, several negative determinants emerged such as the toxicity of the treatment, fears of forgetting to take the medication, difficulties with the galenic formulation and negative beliefs of the family. Conclusion This study demonstrates the need to address the different dimensions of the patient in order to understand his or her behaviour with regard to adherence and to identify the levers for improvement.

Introduction After discussion with the parents, periviable infants can receive either active treatment or palliative care. The rate of active treatment in France is lower than in other developed countries, as is the survival rate of infants in this gestational age range. This study's main objective was to assess the effect of a standardized perinatal management protocol (EXPRIM) on the neonatal outcome of children born before 27 weeks of gestation. Methods A before-and-after study was conducted in the two level-3 hospitals of the Risks and Pregnancy DHU to compare two 16-month periods. The EXPRIM protocol was based on routine administration of prenatal corticosteroid therapy and a scheduled combined obstetric-pediatric group prenatal prognostic evaluation, not based solely on gestational age. The study included all births between 22 weeks and 26 weeks + 6 days of gestation, except in utero deaths diagnosed at admission and medical terminations of pregnancy for fetal malformation, both excluded. The principal endpoint was survival without severe neonatal morbidity. Results The study included 267 women: 116 (128 newborns) in period 1 and 151 (172 newborns) in period 2. The median gestational age at admission to the maternity unit was 2.5 days younger in period 2, and the number of women admitted at 22–23 weeks doubled in period 2 (59 vs 29, respectively). Overall, the rates of live births, NICU transfer, and survival without severe morbidity were similar during the two periods. More infants were liveborn between 22 and 24 weeks in period 2 (66 vs 43). Of all newborns transferred to the NICU, 26 (29%) survived without severe morbidity in period 1 and 46 (39%) in period 2. After multivariate analysis, survival without severe morbidity did not differ significantly. Conclusion Implementation of the EXPRIM protocol led to active treatment of more mothers and their children at the border of viability, and increased the number of children who survived without severe morbidity even if, overall, there was no statistically significant difference in percentage.

In cold-formed steel (CFS) structures, the application of back-to-back built-up channel beams is increasing steadily. The increasing demand of CFS sections as a cost-effective design solution has led to the development of CFS built-up sections. These sections take advantage of higher load-carrying capacities and may be used for longer beam spans. Applications include beam members in CFS wall studs, truss members and floor joists. In such an arrangement, the intermediate screw fasteners at discrete points along the length prevent the individual channel sections from buckling independently. However, limited experimental or finite element (FE) analyses have been reported in the literature for back-to-back built-up channel sections under four-point bending. Furthermore, there is limited investigation of the effect of screw spacing for flexural strength. This paper addressees this issue with 12 experimental test results. Two different cross-sections, referred to as BU75 and BU90, were considered with different screw spacings of 1900 mm, 950 mm and 475 mm. Initial geometric imperfections were measured prior to the bending tests. A nonlinear elasto-plastic FE model was then developed, the results of which showed good agreement against the experimental test results. Using the validated FE model, an extensive parametric study was conducted to investigate the effect of screw spacing on flexural strength of such back-to-back built-up CFS channel beams. In total, the results of 108 parametric analyses are reported. Both the experimental and FE results were compared against the design strengths calculated in accordance with the American Iron and Steel Institute (AISI) and Australian and New Zealand Standards (AS/NZS).

This paper presents an experimental and finite element (FE) investigation into the local-overall buckling interaction behaviour of axially loaded cold-formed steel (CFS) channel section columns. Current design guidelines from the American Iron and Steel Institute (AISI) and the Australian and New Zealand Standards (AS/NZS) recommend the use of a non-dimensional strength curve for determining the axial capacity of such CFS channel section columns. This study has reviewed the accuracy of the current AISI (2016), AS/NZS (2018) and Eurocode (EN 1993-1-3) design guidelines for determining the axial capacity of CFS channel sections under local-overall buckling interaction failure. A total of 40 tests were conducted on CFS channel sections covering stub, short, intermediate, and slender columns with varying thicknesses. A nonlinear FE model was then developed and validated against the test results. The validated FE model was used to conduct a parametric study comprising 70 FE models to review the accuracy of the current design guidelines in accordance with AISI (2016), AS/NZS (2018) and Eurocode (EN 1993-1-3). It was found that the AISI (2016) and AS/NZS (2018) are conservative by 10 to 15% on average when determining the axial capacity of pin-ended CFS channel section columns undergoing local-overall buckling interaction. Eurocode (EN 1993-1-3) design rules were found to lead to considerably more conservative predictions of column axial load capacity for CFS channels.This paper has therefore proposed modifications to the current design rules of AISI (2016) and AS/NZS (2018). The accuracy of proposed design rules was verified using the FE analysis and test results of CFS channel section columns undergoing local-overall buckling interaction.

Background Simulation‐based training in medical education has become a common method to develop both technical and non‐technical skills in teams. Mental rehearsal (MR) is the cognitive act of simulating a task in our heads to pre‐experience tasks imaginatively. It has been used widely to improve individual and collective performance in fields outside healthcare, and offers potential for more efficient training in time‐pressured surgical and medical team contexts. This study aimed to review the available literature to determine the impact of MR on team performance and non‐technical skills in healthcare. Methods MEDLINE, Embase, British Educational Index, CINAHL, Web of Science, PsycInfo and Cochrane databases were searched for the period 1994–2018. The primary outcome measure was improvement in team performance and non‐technical skills. Study quality of RCTs was assessed using the Medical Education Research Quality Instrument. The reported impacts of MR in all included studies were mapped on to the Kirkpatrick framework for evaluation of educational interventions. Results Eight studies with 268 participants were identified that met the inclusion criteria, of which there were six randomized trials, one prospective pragmatic trial and one qualitative study. Three studies found MR to be effective in improving team non‐technical skills. MR practices were varied and often poorly defined. MR benefited team non‐technical skills when it was specifically designed to do so, but was not an automatic consequence of technical MR alone. The majority of studies demonstrated benefits of MR for technical performance, but only three showed positive impacts on teamwork. Overall the studies were of low quality and lacked sufficient discriminatory focus to examine impacts on teamwork dynamics. Conclusion MR can improve technical performance, but the benefits on non‐technical skills are less clear. Future research should look at longitudinal mixed‐method evaluation designs and focus on real clinical teams., This indepth critical analysis of team‐based mental rehearsal activities and their effect on surgical team non‐technical skills and team performance found that mental rehearsal may provide a free and easy‐to‐use tool to augment surgical team performance and improve teamwork. More work is needed to quantify and fully understand the effect of mental rehearsal. Team rehearsals to improve outcomes

International audience; Complications with bilateral sagittal split osteotomy (BSSO) can sometimes result from surgical inexperience. Our aim was to present a 3-dimensional printed mandibular model for BSSO training in a maxillofacial surgical education programme. A polymethacrylate mandibular model obtained from mandibular cone-beam computed tomographic (CT) images was designed and printed for use in training. Twenty-four residents were each asked to do a BSSO according to the Epker/Dal-Pont technique. The session was conducted as a simulation course with a final debriefing. A questionnaire before and after the test was filled in using a 10-point Likert scale to assess the participants' knowledge. The mandibular model provided a realistic way of handling the trabecular bone after cortical osteotomy, as well as in the splitting phase. Significant increases in knowledge and surgical skills were noted for all steps of the BSSO, particularly regarding the use of the piezoelectric device for osteotomy, and for management of wisdom teeth in the splitting zone (3.00 ±2.16 to 6.95 ±2.06 and 2.73 ±1.91 to 5.75 ±2.63, respectively; p1=0.0002 and p2=0.0003). We think that this is a valuable printed mandibular model for the development of surgical skills for BSSO in maxillofacial surgical residents.

Background Learning in the workplace maximises relevance to clinical practice and facilitates the education of the whole multiprofessional team. Provision of structured teaching is becoming increasingly challenging with shift pattern working and staff shortages. This article describes a simulation course designed to facilitate team learning to improve the care of nephrology patients, and presents outcome data over 2 years. Methods A full-day course, using high fidelity manikins, was designed for nephrology specialty trainees and nurse specialists. Nineteen learners (eleven specialty trainees and eight nurse specialists) and nine multidisciplinary team faculty members attended. Evaluation used pre- and post-course assessments, with a 1-year follow-up questionnaire. Results Following the course, improved knowledge scores, 56% to 72% (PConclusions This course improved knowledge and confidence in managing nephrology scenarios across the multidisciplinary learning group, and the model could be used in other hospital specialties.

Background Mental Rehearsal (MR) the cognitive act of simulating a task in our heads to pre-experience events imaginatively. It has been used widely to improve individual and collective performance in fields outside healthcare and offers potential for more efficient training in time pressured surgical and medical team contexts. The study aims to review the current systematic review literature to determine the impact of MP on surgical performance and learning. Methods Medline, Embase, British Educational Index, CINAHL, Web of Science PsycINFO, Cochrane databased were searched in the period 1994–2018. The primary outcomes measure were performance improvements in surgical technical skills, stress reduction, confidence and team performance. Study quality of the Systematic Reviews was assessed using AMSTAR 2, a critical appraisal tool for systematic reviews. The reported impacts of MP in all included studies were mapped onto Kirkpatrick’s framework for the evaluation of educational interventions. Results Six Systematic reviews were identified which met the inclusion criteria, of which all reported positive and varying benefits of MP on surgical performance, confidence, and coping strategies. However, reported impacts on a modified Kirkpatrick’s framework did not exceed level 3. Mental practice was described in terms of mental imagery and mental rehearsal with most authors using each of the terms in their search strategies. The impacts on transfer to practice and the long- term acquisition of skills, but also personal uptake of mental practice routines were not reported. Conclusion The majority of studies demonstrate benefits of MP for technical performance. Overall the systematic reviews were of medium to high quality. However, studies lacked a sufficiently articulated evaluation methodology to examine impacts beyond the immediate experimentations. This is also due to the limitations found in the primary studies. Future research should look at longitudinal mixed method evaluation designs and focus on real clinical teams.

Pressure therapy (PT) is commonly used to manage hypertrophic scars. It is often based on the use of elastic pressure garments, which are poorly suited for a facial localization. We describe the conception, fabrication, and use of a custom-made PT facial mask for primary prevention of hypertrophic scarring of complex facial wounds. The main advantage of the device is that it is quick and easy to manufacture in a conventional prosthetics laboratory, with a good level of observance and tolerance in our experience of 20 treated patients.

Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL-17A compared to control mice that resulted in an IL-17/IFN-γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL-10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL-10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL-10/IFN-γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.

Objectives Numerous adverse drug events (ADEs) are not identified by doctors in medical emergencies, and they are a barrier to optimal treatment of patients. Identification of the factors that influence awareness of ADEs by doctors could allow events that compromise patient safety to be avoided. The aims of this study were to quantify the recognition of ADEs by emergency room (ER) doctors and to identify the factors associated with the lack of identification of drug-related risks. Methods This study was carried out at the ER of a French teaching hospital between January 1, 2014, and the December 31, 2017. A previously used form was administered to the patients being treated in the ER, and it was completed using medical files to identify ADEs. The ADEs were then validated by a doctor and a senior pharmacist. Results Of the 1870 included patients, 279 (14.9%) exhibited an ADE. Of these 279 ADEs, 201 (72%) had been identified by the doctor. The probability of an ADE being identified was higher when the drug was directly linked with the main ailment of the patient (odds ratio, 1.72; 95% confidence interval, 1.01-2.97). Adverse drug events were identified less well when their severity was limited (spontaneous regression without treatment) (odds ratio, 0.5; 95% confidence interval, 0.27-0.93). Conclusions This study showed that ADEs are identified less well when their severity is limited, as well as when the ADE is not directly linked with the main ailment of the patient.

International audience; In March 2020, a severe respiratory syndrome developed in a cat, 1 week after its owner received positive test results for severe acute respiratory syndrome coronavirus 2. Viral RNA was detected in the cat's nasopharyngeal swab samples and vomitus or feces; immunoglobulin against the virus was found in convalescent-phase serum. Human-to-cat transmission is suspected.

Neutrophils help to clear pathogens and cellular debris, but can also cause collateral damage within inflamed tissues. Prolonged neutrophil residency within an inflammatory niche can exacerbate tissue pathology. Using both genetic and pharmacological approaches, we show that BCL-XL is required for the persistence of neutrophils within inflammatory sites in mice. We demonstrate that a selective BCL-XL inhibitor (A-1331852) has therapeutic potential by causing apoptosis in inflammatory human neutrophils ex vivo. Moreover, in murine models of acute and chronic inflammatory disease, it reduced inflammatory neutrophil numbers and ameliorated tissue pathology. In contrast, there was minimal effect on circulating neutrophils. Thus, we show a differential survival requirement in activated neutrophils for BCL-XL and reveal a new therapeutic approach to neutrophil-mediated diseases.

Built-up box sections are becoming increasingly popular for column members in cold-formed steel (CFS) construction; uses of such sections include CFS trusses, space frames, and portal frames. In this article, the built-up box sections are formed through two identical lipped channels connected at their flanges with self-drilling screws. In such an arrangement, independent buckling of the individual channels is prevented by the screws. This paper presents an experimental investigation on axial capacity of built-up CFS box sections. Tests were conducted for different values of slenderness from short to slender columns. In total, the results from 16 experimental tests are reported. Of these, 8 tests were conducted on built-up CFS box sections and the remaining 8 tests were conducted on single channel sections. Load-axial shortening relationship, and failure modes are discussed for built-up columns. Nonlinear finite element (FE) models were developed for built-up CFS box sections and single channels. FE models considered material nonlinearities, initial imperfections and modeling of intermediate fasteners. FE results showed good agreement against the test results. A parametric study was conducted which comprises 148 models to investigate the effect of fastener spacing on axial capacity of built-up CFS box sections. Both FE and test results were compared against the design strengths calculated in accordance with the American Iron and Steel Institute (AISI) and Australian and New Zealand Standards (AS/NZS). From the comparison, it was observed that the AISI & AS/NZS are conservative by around 17% while determining the axial capacity of such built-up CFS box columns.

A finite element model is described in this paper, which investigates the behavior of CFS built-up un-lipped channel sections, connected back to back with the help of intermediate web fasteners, subjected to axial load. Finite element package ABAQUS was used to develop the model for built-up columns, which were validated against the test results reported by the authors recently on another paper. Material non-linearity and initial imperfections were included in the FEA model. A parametric study was conducted using the validated FEA model to investigate the effect of screw spacing on axial strength. Axial strengths obtained from the FEA model were compared against the AISI&AS/NZS design strengths; obtained comparisons showed that the AISI&AS/NZS standards were un-conservative for stub and short columns which failed by local buckling whereas the standards were over-conservative for columns failed through overall buckling.

A combined experimental and numerical investigation was conducted into evaluating the influence of the geometry of a water-filled container on maximising the reduction in deformation it provides to a high-strength steel plate subject to localised blast loading. Experiments were conducted with a range of novel container shapes including a cone, inverted cone, diamond and mushroom. In addition to these container shapes, an array of water bottles known as a kinetic energy defeat device (KEDD) and a high performing quadrangular container design were also evaluated. The performance of each container was evaluated in terms of both the reduction in deformation of a steel target plate and the efficiency of the mitigation in terms of the reduction per unit mass of water. The numerical simulations were found to provide adequate predictions for the novel container shapes. They were then used to isolate the differences in target loading for each container type. Further numerical simulations were then performed to identify improvements in the design of the best performing containers. The best performing novel geometries were the mushroom and inverted cone shaped containers, which are more effective at radially spreading the water. However, the mushroom shaped container was the only container found to outperform the most efficient quadrangular container on a mass efficiency basis. The results of this investigation can be used to assist in the design of water-filled containers that are used as part of a near-field blast protection system on an armoured vehicle or other protected structure.

We investigated the incidence of tuberculosis (TB) in patients with newly diagnosed oral cancer and analyzed the risk factors for TB development and mortality in oral cancer patients. We used Taiwan’s National Health Insurance Database to determine the incidence of TB and to analyze the risk factors for TB in patients newly diagnosed with oral cancer. From 2000 to 2011, we identified 40,327 oral cancer patients and the same number of subjects from the general population matched for sex, age, and comorbidities at a 1:1 ratio. Compared with the matched cohort, oral cancer patients exhibited a higher risk for TB (adjusted hazard ratio (aHR) 2.36, 95% confidence interval (CI) 2.06–2.71). Age ≥ 50 (aHR 1.90, 95% CI 1.57–2.29), being male (aHR 1.98, 95% CI 1.36–2.89), having diabetes mellitus (aHR 1.31, 95% CI 1.05–1.64), alcohol use disorder (aHR 1.42, 95% CI 1.06–1.89), human immunodeficiency virus (HIV) (aHR 8.24, 95% CI 2.05–33.14), chemotherapy (aHR 1.41, 95% CI 1.15–1.72), and radiotherapy for oral cancer (aHR 1.92, 95% CI 1.57–2.36) were identified as independent risk factors for TB in oral cancer patients. Hyperlipidemia was an independent protective factor for TB in oral cancer patients. Old age, male sex, diabetes mellitus, alcohol use disorder, and HIV were independent risk factors for TB in patients with oral cancer. High-risk oral cancer patients should be regularly screened for TB, especially those in endemic areas.

Background Children’s role in SARS-CoV-2 epidemiology remains unclear. We investigated an initially unnoticed SARS-CoV-2 outbreak linked to schools in northern France, beginning as early as mid-January 2020. Aims This retrospective observational study documents the extent of SARS-CoV-2 transmission, linked to an affected high school (n = 664 participants) and primary schools (n = 1,340 study participants), in the context of unsuspected SARS-CoV-2 circulation and limited control measures. Methods Between 30 March and 30 April 2020, all school staff, as well as pupils and their parents and relatives were invited for SARS-CoV-2 antibody testing and to complete a questionnaire covering symptom history since 13 January 2020. Results In the high school, infection attack rates were 38.1% (91/239), 43.4% (23/53), and 59.3% (16/27), in pupils, teachers, and non-teaching staff respectively vs 10.1% (23/228) and 12.0% (14/117) in the pupils’ parents and relatives (p Conclusions Viral circulation can occur in high and primary schools so keeping them open requires consideration of appropriate control measures and enhanced surveillance.

Background Children have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections. Aim We tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection. Methods We set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections. Results Prevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children. Conclusion Prior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

SummaryBackgroundThe Oise department in France has been heavily affected by COVID-19 in early 2020.MethodsBetween 30 March and 4 April 2020, we conducted a retrospective closed cohort study among pupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located in Oise. Participants completed a questionnaire that covered history of fever and/or respiratory symptoms since 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. The infection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2 infection based on antibody detection. Blood samples from two blood donor centres collected between 23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2 antibodies.FindingsOf the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2 antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infection fatality rate was 0% (one-sided 97.5% CI = 0 - 2.1). Nine of the ten participants hospitalised since mid-January were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4 –9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%, respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P InterpretationThe relatively low IAR observed in an area where SARS-CoV-2 actively circulated weeks before confinement measures indicates that establishing herd immunity will take time, and that lifting these measures in France will be long and complex.FundingInstitut Pasteur, CNRS, Université de Paris, Santé publique France, Labex IBEID (ANR-10-LABX-62-IBEID), REACTing, EU grant Recover, INCEPTION project (PIA/ANR-16-CONV-0005).Research in contextEvidence before the studyThe first COVID-19 cases in France were reported on 24 January 2020. Substantial transmission has occurred since then, with the Oise department, north of Paris, one of the heaviest affected areas in the early stages of the epidemic in France. As of 13 April 2020, 98,076 cases had been diagnosed in France, including 5,379 deaths.Epidemiological and clinical characteristics of patients with COVID-19 have been widely reported, but this has largely been centred on cases requiring medical care. What remains unclear at this stage is the extent to which SARS-CoV-2 infections may be asymptomatic or present as subclinical, non-specific symptoms. While extensive contact tracing has identified asymptomatic infections using RT-PCR testing, serologic detection of anti-SARS-CoV-2 antibodies is needed to determine the real infection attack rate and the proportion of all infections that are asymptomatic or subclinical.Added value of this studyUsing a combination of serologic assays with high sensitivity and specificity for anti-SARS-CoV-2 antibodies, we conducted a retrospective closed cohort study. In a high school linked to a cluster of COVID-19 in the Oise department, we showed an overall infection attack rate (IAR) of 40.9% in the high school group, and 10.9% in parents and siblings of the pupils. The proportion of infected individuals who had no symptoms during the study period was 17.0%.Implications of all of the available evidenceThe relatively low IAR in this area where SARS-CoV-2 actively circulated before confinement measures were introduced indicates that establishing herd immunity will take time, and that the lifting of these measures in France will be long and complex.

The COVID-19 pandemic posed a major challenge for the UK National Health Service to scale up acute and intensive care beds at a scale never before conceived in peacetime history. To manage this upscaling, hospitals were tasked to upskill and cross-skill majority of clinical staff to be redeployed in COVID-19 clinical areas. Responding to this challenge education departments employed a variety of strategies to provide this training to staff in the space of a few weeks, as the COVID-19 pandemic surge arrived. In a University teaching hospital in London, one of the hotspots of COVID-19 in the UK during the first surge, approximately 1000 clinical staff were trained through military-style ‘Bootcamps’. The concept, design, delivery and evaluation of this exercise offers a unique opportunity to reflect on both the educational and behavioural aspects important to learning. This article analyses the reflections contextualises and captures the lessons for organisations and educators alike to apply in future massive responses. were required to deliver this training. What this exercise has demonstrated that firstly, it has consolidated our belief in thepotential for adapting pre-existing simulation scenarios, developing learning protocols working closely with frontline clinicians, aligned with organisational goals. Secondly, that educationalists benefit from working closely with frontline learners in designing, shaping and delivering content, thus keeping it relevant, meaningful and contemporary. Finally, it has shown that byte-sized programmes working with a flexible cohort of learners from wide-ranging backgrounds, and delivered with a 'drop-in-when-one-can' model is effective - in reaching within complex organisational hierarchy. Thus offers a frameworkfor future rapid-rollout of educational interventions. &nbsp

The management of diabetic foot infections is frequently a dead end for surgeons and infectious disease specialists. When the pathogen to be treated is not resistant to conventional antibiotics, the latter tend to unbalance the intestinal microbiota, which is linked to multiple pathologies. A local treatment with bacteriophages, in addition to being as much or even more effective than antibiotics from a clinical and microbiological point of view, makes it possible to respect the patient’s microbiota. These results suggest that the use of this therapeutic alternative is a major avenue and that the introduction of recommendations for their use is now necessary., Diabetes is marked by a range of complications, including chronic infections that can lead to limb amputation. The treatment of infected wounds is disrupted by arteriopathies that reduce tissue perfusion as well as by the critical development of bacterial resistance. We evaluated the impact of a local application of bacteriophages compared to that of a per os administration of amoxicillin-clavulanic acid in a mouse model of Staphylococcus aureus wound infection. We found that phage treatment resulted in improved clinical healing and a reduction in local bacterial load at 7 and 14 days postinfection. Unlike antibiotics, phage therapy did not deplete the intestinal microbiota of treated animals. Amoxicillin resulted in a reduction of alpha and beta diversities of the murine microbiota and disturbed architecture even 7 days after the end of treatment, whereas phage treatment did not impinge on the microbiota. IMPORTANCE The management of diabetic foot infections is frequently a dead end for surgeons and infectious disease specialists. When the pathogen to be treated is not resistant to conventional antibiotics, the latter tend to unbalance the intestinal microbiota, which is linked to multiple pathologies. A local treatment with bacteriophages, in addition to being as much or even more effective than antibiotics from a clinical and microbiological point of view, makes it possible to respect the patient’s microbiota. These results suggest that the use of this therapeutic alternative is a major avenue and that the introduction of recommendations for their use is now necessary.

Objectives The economic impact of Patient blood management (PBM) must be assessed beyond the acquisition cost of blood products alone. The estimate of indirect costs may vary depending on the organization and the elements taken into account. The transposition of data from the literature into a specific local context is therefore delicate. The objective of this work was to evaluate the overall cost of red blood cell concentrate (RBC) transfusion from a French healthcare establishment point of view. Methods We carried out an activity based costing analysis in our hospital for the year 2018. The steps of the transfusion process and additional costs were detailed and cumulated (resource consumption, labor time, frequency) to populate the ABC model. Several scenarios were developed focusing either on RBC, all blood products or the surgical activity, and a univariate sensitivity analysis was conducted. Results The average total cost of transfusion, including acquisition cost, was 339,64 euros per RBC transfused. The cost of administration was 138.41 euros/RBC. Focusing only on surgical activities increased this cost (152.43 euros) while taking all blood products into account reduced it (92.49 euros). Conclusion The difference in our results with the literature confirms the local variability in the cost of transfusion, which may affect the economic impact of PBM. Our study related to the specific context of a single French institution has limitations that a multicenter study would clarify in order to carry out economic modelling of transfusion optimization and alternatives and to guide the choice of PBM strategies at the national level.

Background Mycoplasma genitalium (MG) is an emerging pathogen among men who have sex with men (MSM) with raising rates of antibiotic resistance. This study assessed the prevalence and incidence of MG infection in MSM enrolled in the open-label phase of the ANRS IPERGAY trial with on-demand tenofovir disoproxil fumarate/emtricitabine for human immunodeficiency virus prevention and the impact of doxycycline post-exposure prophylaxis (PEP). Methods 210 subjects were tested at baseline and at 6 months by real-time PCR assays for MG detection in urine samples and oropharyngeal and anal swabs. Resistance to azithromycin (AZM), to fluoroquinolones (FQs), and to doxycycline was investigated in the French National Reference Center of Bacterial Sexually Transmitted Infections (STIs). Results The all-site prevalence of MG at baseline was 10.5% (6.3% in urine samples, 4.3% in anal swabs, 0.5% in throat swabs) and remained unchanged at 6 months whether or not PEP was used: 9.9% overall, 10.2% with PEP, 9.6% without. The overall rate of MG resistance (prevalent and incident cases) to AZM and FQs was 67.6% and 9.1%, respectively, with no difference between arms. An in vivo mutation of the MG 16S rRNA, which could be associated with tetracycline resistance, was observed in 12.5% of specimens tested. Conclusions The prevalence of MG infection among MSM on pre-exposure prophylaxis was high and its incidence was not decreased by doxycycline prophylaxis with a similar high rate of AZM and FQ resistance, raising challenging issues for the treatment of this STI and supporting current recommendations to avoid testing or treatment of asymptomatic MG infection.

BackgroundChildren have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS).MethodsThis cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup).FindingsSARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55·6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66·9 −100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection.InterpretationPrior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection.Evidence before this studyChildren seem to be less likely affected by SARS-CoV-2 infection and clinical course of COVID-19 is less severe than in adults. As those asymptomatic or mildly symptomatic children are underdiagnosed and their viral loads are comparable to those of adults, they may act as an asymptomatic reservoir for the spread of the virus. One explanation of the difference between the adult and the pediatric infectious profile might be that infection with seasonal human coronaviruses, which is very frequent from a very young age, could lead to cross protective immunity. We searched in PubMed, MedRxiv and BioRxiv for publications from inception to June 15, 2020, using the terms “COVID-19, SARS-CoV-2, children, serology, Kawasaki, Corona Virus”.Added value of this studySARS-CoV-2 mean prevalence rate was 11.7% from April 1 to June 1 and neutralizing antibodies were found in 55% of the tested seropositive children. Among patients with a Multisystem Inflammatory Syndrome, Kawasaki-like disease, 70% were SARS-CoV-2 seropositive and had neutralizing antibodies. COVID-19 and MIS attack rates, and anti-SARS-CoV-2 antibodies titres were not significantly impacted by prior seasonal coronavirus infection.Implications of all the available evidencePrior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children As antibodies against seasonal coronaviruses are very frequent and as these viruses circulate efficiently in human populations every winter, our results question to what extent the concept of herd immunity based on circulating antibodies can be applied to seasonal coronaviruses and possibly SARS-CoV-2.

International audience

Phytotherapy is the main complementary medicine for which patients afflicted with cancer have recourse but the associated consumption of phytotherapy products gives rise to a risk of interaction with anticancer agents. The aim of this prospective study was to measure the prevalence of the consumption of phytotherapy products as well as their interactions with anticancer agents in a cohort of patients from January 2018 to August 2019. Patients hospitalized in the conventional hematology unit and outpatients who had their prescriptions for oral anticancer agents filled at the hospital pharmacy were questioned about consumption of phytotherapy products by pharmacy externs trained in pharmaceutical interviews. Among the 110 hospitalized patients who answered the questionnaire, 40% (n = 44) used phytotherapy and 5 of them continued to consume it during the cycles of injectable chemotherapy. As a result, 10 interactions were found between the plants and the anticancer agents (prevalence of 27%). Among the 59 outpatients, 17% (n = 10) consumed phytotherapy. Eight interactions were identified (prevalence of 80%). The potential consequences were an increase or a decrease in the concentration of the anticancer agents and an increase in the risk of bleeding, hepatoxicity, and hypokalemia. The consumption of phytotherapy was unknown by a health professional for 44% of hospitalized patients and 60% of the outpatients. The risk of interactions between plants and anticancer agents is not negligible and professionals should be cognizant of this in their daily practice. The availability of tools for training and detection of interactions is indispensable for managing patients undergoing onco-hematology treatments.

International audience; A major gap in the Plasmodium vivax elimination toolkit is the identification of individuals carrying clinically silent and undetectable liver-stage parasites, called hypnozoites. This study developed a panel of serological exposure markers capable of classifying individuals with recent P. vivax infections who have a high likelihood of harboring hypnozoites. We measured IgG antibody responses to 342 P. vivax proteins in longitudinal clinical cohorts conducted in Thailand and Brazil and identified candidate serological markers of exposure. Candidate markers were validated using samples from year-long observational cohorts conducted in Thailand, Brazil and the Solomon Islands and antibody responses to eight P. vivax proteins classified P. vivax infections in the previous 9 months with 80% sensitivity and specificity. Mathematical models demonstrate that a serological testing and treatment strategy could reduce P. vivax prevalence by 59-69%. These eight antibody responses can serve as a biomarker, identifying individuals who should be targeted with anti-hypnozoite therapy.

It is of paramount importance to evaluate the prevalence of both asymptomatic and symptomatic cases of SARS-CoV-2 infection and their antibody response profile. Here, we performed a pilot study to assess the levels of anti-SARS-CoV-2 antibodies in samples taken from 491 pre-epidemic individuals, 51 patients from Hôpital Bichat (Paris), 209 pauci-symptomatic individuals in the French Oise region and 200 contemporary Oise blood donors. Two in-house ELISA assays, that recognize the full-length nucleoprotein (N) or trimeric Spike (S) ectodomain were implemented. We also developed two novel assays: the S-Flow assay, which is based on the recognition of S at the cell surface by flow-cytometry, and the LIPS assay that recognizes diverse antigens (including S1 or N C-terminal domain) by immunoprecipitation. Overall, the results obtained with the four assays were similar, with differences in sensitivity that can be attributed to the technique and the antigen in use. High antibody titers were associated with neutralisation activity, assessed using infectious SARS-CoV-2 or lentiviral-S pseudotypes. In hospitalized patients, seroconversion and neutralisation occurred on 5-14 days post symptom onset, confirming previous studies. Seropositivity was detected in 29% of pauci-symptomatic individuals within 15 days post-symptoms and 3 % of blood of healthy donors collected in the area of a cluster of COVID cases. Altogether, our assays allow for a broad evaluation of SARS-CoV2 seroprevalence and antibody profiling in different population subsets.

International audience; Here, we produced a synthetic polymer having adequate biocompatibility, biodegradability, and bioresorbability, as well as mechanical properties for applications in bone tissue engineering. We used the fused deposition modeling (FDM) based 3D printing approach in order to produce biomimetic biodegradable scaffolds made of polylactic acid (PLA). We strengthened these scaffolds by addition of exfoliated boron nitride (EBN) as filler. We demonstrated the presence of EBN by physicochemical analysis using Raman spectroscopy and X-ray diffraction (XRD). Using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), we found that EBN incorporation did not influence the transition temperature, but reduced the polymer crystallinity. Scanning electron microscopy for morphology evaluation showed a mean scaffold pore size of 500 μm. EBN incorporation did not affect the scaffold mechanical properties (tensile test), but modified the surface roughness. Moreover, contact angle quantification indicated that the surface of PLA/EBN scaffolds was hydrophilic and that of PLA scaffolds hydrophobic. Finally, the results of the cytotoxicity, cell attachment, and proliferation experiments using MG-63 and MC3T3 cells indicated that PLA scaffolds filled with EBN were nontoxic and compatible with osteoblastic cells and also promoted the scaffold mineralization by MG-63 cells. Altogether, our results suggest that this 3D printed nanocomposite scaffold is suitable for tissue engineering.

Background and importance Since 2011, the French drug agency has sponsored an expanded access programme to make Malacef (artesunate) available for the treatment of severe malaria. This drug has not yet been approved by European and US pharmaceutical agencies, while it is available in China and several African countries. Aim and objectives The aim of this study was to assess the efficiency and real life safety of intravenous artesunate (IA) for the treatment of severe malaria. Material and methods We performed a retrospective, monocentric, observational study. All patients who received IA from January 2016 to September 2019 were included. Data were collected from the pharmacy service computerised system, patient records and nominative expanded access authorisation forms. The primary endpoint was efficiency, assessed by the microscopic negativation of the parasitaemia. The secondary endpoint was safety, assessed by monitoring haemoglobin, transaminases, blood platelets, kaliaemia and creatinaemia. Results Sixty-nine patients were treated with IA in our hospital. Among all patients, 59 patients (86%) had not received chemoprophylaxis. The average time between leaving the infected zone and hospital admission was 11±7 days. Patients received 3.1±0.7 doses of IA. Sixty-five patients presented at least one criterion requiring the use of IA (the most common was >4% hyperparasitaemia in 39 patients). Forty-six (67%) patients had a microscopic negativation of their parasitaemia after 3 days of treatment and 100% at day 7. Regarding tolerance, only 52% had a decrease in their haemoglobin level of >2 g/L during the whole hospitalisation. Platelets and transaminase values were normal (184–440 G/L and Conclusion and relevance The IA treatment was effective and well tolerated in all patients. These results seem to be in favour of a broader and ease of use of IA. References and/or acknowledgements No conflict of interest.

Background and importance There are few data on the use of herbal medicines and the potential risks of herbal drug interactions (HDI) with oral anticancer drugs (OACD), even though their consumption is increasing. Aim and objectives The aim of this study was to collect data on consumption of medicinal plants by patients on OACD and to assess the potential HDI and their knowledge among patients and physicians. Material and methods This was an observational study conducted within a hospital outpatient pharmacy for 6 weeks. Patient interviews were carried out using a questionnaire on the following themes: phytotherapy products consumed, point of purchase, consumption objectives and awareness of health professionals. Potential HDI were evaluated using the MSKCC and Hedrine databases. A targeted questionnaire was sent to haematologists and physicians to assess their knowledge and needs. Results Among the 59 included patients receiving OACD, 17% (n=10) were using phytotherapy. Of these 10 patients, 4 were taking herbal medicine as a complement to their anticancer treatment and the other 6 for another purpose (well being, cough, cold). The majority (70%) consumed on a regular basis on average of 2.4 different products. Four (40%) had informed a professional of their consumption. The products were mainly purchased in organic product shops (40%) and in pharmacies (20%), on the advice of a member of the family and friends (50%) or a health professional (40%). Five interactions were found. These were HDI at risk of hyperkalaemia, increased risk of bleeding and toxicity of OACD by reduced metabolism. Among the 21 physicians who answered the survey, a difference in practice between general practitioners and haematologists was highlighted. All doctors were seeking training in complementary medicine. Conclusion and relevance The consumption of herbal medicines in patients treated with OACD is not negligible. Patients appear to be poorly or not informed about HDI, as well as doctors. The pharmacist has a major role to play in this context. Distribution of a recommendation guide could reduce the risk of HDI. References and/or acknowledgements 1. Boiteux-Jurain M, Gerard B, Perrin-Bonnot, et al. Interactions between phytotherapy and oral anticancer drugs: development of a tool to assist in pharmaceutical analysis. Hosp Pharm Clin 2017;52(1). No conflict of interest.

Background and importance Since 2015, a pharmacist/resident duo has been conducting drug reconciliation and medication review in the orthopaedic surgery department. They participate in multidisciplinary team (MDT) meetings to discuss patient with osteomyelitis. These clinical case conferences take place every week to determine the most suitable surgical and medical treatments for individual patients. Aim and objectives The objective of this study was to assess the impact of the pharmacist’s involvement in the MDT meetings on the medical management of patients with osteomyelitis. Material and methods A prospective study was conducted on all pharmaceutical recommendations (PRs) made during the MDT meetings. The data collection period was from June to September 2019. All patients had their medications reconciled previously. We used the drug related problem classification system (DRP)1 to rate the PRs and to identify the problems, causes, types and outcomes of these interventions. Results Of the 17 MDT meetings, 220 patient records were reviewed and 24 PRs were identified. The pharmacist provided information about the patient, along with treatment and recommendations in 38% of cases (renal function, galenic alternatives, previous prescriptions, availability and cost of the drug). For 62% of patients, this information changed the therapeutic decision: choice of antibiotic (33%), potential interactions with long term medications (29%), need to add a drug (12.5%) and optimal dosing for 8% of cases (subtherapeutic in 4%, overdosing in 4%). A large majority (95.8%) of the recommendations were accepted by the prescribers. The most common class of medication was systemic antibiotics (88%). Conclusion and relevance The work of medication reconciliation and checking prescriptions was carried out by the pharmacist in the orthopaedic department and this allowed better understanding of the patient and their medication. By participating in MDT meetings, the pharmacist can communicate directly with the prescriber and contribute to clinical decision making regarding anti-infective medications. The clinical pharmacist provided a comprehensive review and therefore played a major role in the medical management of patients with osteomyelitis. References and/or acknowledgements https://www.pcne.org/upload/files/334_PCNE_classification_V9-0.pdf No conflict of interest.

International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, in 2019, is responsible for the COVID-19 pandemic. It is now accepted that the wild fauna, probably bats, constitute the initial reservoir of the virus, but little is known about the role pets can play in the spread of the disease in human communities, knowing the ability of SARS-CoV-2 to infect some domestic animals. In this cross-sectional study, we tested the antibody response in a cluster of 21 domestic pets (9 cats and 12 dogs) living in close contact with their owners (belonging to a veterinary community of 20 students) in which two students tested positive for COVID-19 and several others (n = 11/18) consecutively showed clinical signs (fever, cough, anosmia, etc.) compatible with COVID-19 infection. Although a few pets presented many clinical signs indicative for a coronavirus infection, no antibodies against SARS-CoV-2 were detectable in their blood one month after the index case was reported, using an immunoprecipitation assay. These original data can serve a better evaluation of the host range of SARS-CoV-2 in natural environment exposure conditions.

Background: The Oise department in France has been heavily affected by COVID-19 in early 2020. Methods: Between 30 March and 4 April 2020, we conducted a retrospective closed cohort study among pupils, their parents and siblings, as well as teachers and non-teaching staff of a high-school located in Oise. Participants completed a questionnaire that covered history of fever and/or respiratory symptoms since 13 January 2020 and had blood tested for the presence of anti-SARS-CoV-2 antibodies. The infection attack rate (IAR) was defined as the proportion of participants with confirmed SARS-CoV-2 infection based on antibody detection. Blood samples from two blood donor centres collected between 23 and 27 March 2020 in the Oise department were also tested for presence of anti-SARS-CoV-2 antibodies. Findings: Of the 661 participants (median age: 37 years), 171 participants had anti-SARS-CoV-2 antibodies. The overall IAR was 25.9% (95% confidence interval (CI) = 22.6-29.4), and the infection fatality rate was 0% (one-sided 97.5% CI = 0 - 2.1). Nine of the ten participants hospitalised since mid-January were in the infected group, giving a hospitalisation rate of 5.3% (95% CI = 2.4 –9.8). Anosmia and ageusia had high positive predictive values for SARS-CoV-2 infection (84.7% and 88.1%, respectively). Smokers had a lower IAR compared to non-smokers (7.2% versus 28.0%, P

International audience; BACKGROUND: In France, many parents have lost confidence in vaccinations, which has a direct impact on immunization coverage. Pharmacists, like other health professionals, often encounter parents exhibiting vaccine distrust. METHODS: Using a survey distributed in a school and in a number of volunteering pharmacies, the objective of this study was to gain a better understanding of the views and the attitude of parents in regard to vaccination of their children. RESULTS: Our results show that the main concerns were in regard to vaccine adjuvants, the risk of short- and long-term adverse effects, and the risk of developing a disease or a disability as a result of vaccination. The parents, although they tended to express a degree of reluctance and apprehension, in general, they were not opposed to vaccination, and they sought objective scientific information and full transparency regarding all aspects of vaccine composition, adverse effects, and effectiveness. Cooperation of all the parties involved in the health system on this subject is essential for a seamless chain of care and to improve vaccination coverage. CONCLUSION: The information collected, combined with a review of the international literature, allow avenues for dialogue adapted to parents' opinions to be established and thus assist health professionals to communicate effectively regarding vaccines, which is a bona fide public health issue.

In cold-formed steel structures, such as trusses, wall frames and portal frames, the use of back-to-back built-up cold-formed steel channel sections are becoming increasingly popular. In such an arrangement, intermediate fasteners are required at discrete points along the length, preventing the channel-sections from buckling independently. Current guidance in the AISI A obtained comparisons showed that AISI& AS/NZS standards are un-conservative for stub and short columns which were failed by local buckling whereas standards were over-conservative for the strength of intermediate and slender columns which were failed mainly by overall member buckling. This paper has therefore proposed improved design rules and verified their accuracy using finite element analysis and test results of back-to-back built-up cold-formed channel sections, subjected to axial compression.

Purpose This paper aims to present the design optimisation using genetic algorithm (GA) to achieve the highest strength to weight (S/W) ratio, for cold-formed steel residential roof truss. Design/methodology/approach The GA developed in this research simultaneously optimises roof pitch, truss configurations, joint coordinates and applied loading of typical dual-pitched symmetrical residential roof truss. The residential roof truss was considered with incremental uniform distributed loading, in both gravitational and uplift directions. The structural analyses of trusses were executed in this GA using finite element toolbox. The ultimate strength and serviceability of trusses were checked through the design formulation implemented in GA, according to the Australian standard, AS/NZS 4600 Cold-formed Steel Structures. Findings An optimum double-Fink roof truss which possess highest S/W ratio using GA was determined, with optimum roof pitch of 15°. The optimised roof truss is suitable for industrial application with its higher S/W ratio and cost-effectiveness. The combined methodology of multi-level optimisation and simultaneous optimisation developed in this research could determine optimum roof truss with consistent S/W ratio, although with huge GA search space. Research limitations/implications The sizing of roof truss member is not optimised in this paper. Only single type of cold-formed steel section is used throughout the whole optimisation. The design of truss connection is not considered in this paper. The corresponding connection costs are not included in the proposed optimisation. Practical implications The optimum roof truss presented in this paper is suitable for industrial application with higher S/W ratio and lower cost, in either gravitational or uplift loading configurations. Originality/value This research demonstrates the approaches in combining multi-level optimisation and simultaneous optimisation to handle large number of variables and hence executed an efficient design optimisation. The GA designed in this research determines the optimum residential roof truss with highest S/W ratio, instead of lightest truss weight in previous studies.

Kawasaki disease (KD) is an inflammatory disorder of young children, associated with vasculitis of the coronary arteries with subsequent aneurysm formation in up to one-third of untreated patients. Those who develop aneurysms are at life-long risk of coronary thrombosis or the development of stenotic lesions, which may lead to myocardial ischaemia, infarction or death. The incidence of KD is increasing worldwide, and in more economically developed countries, KD is now the most common cause of acquired heart disease in children. However, many clinicians in the UK are unaware of the disorder and its long-term cardiac complications, potentially leading to late diagnosis, delayed treatment and poorer outcomes. Increasing numbers of patients who suffered KD in childhood are transitioning to the care of adult services where there is significantly less awareness and experience of the condition than in paediatric services. The aim of this document is to provide guidance on the long-term management of patients who have vascular complications of KD and guidance on the emergency management of acute coronary complications. Guidance on the management of acute KD is published elsewhere.

In cold-formed steel structures, such as trusses and portal frames, the use of back-to-back gapped built-up cold-formed steel channel-sections for column members are becoming increasingly popular. In such an arrangement, the lowest flexural buckling mode may not necessarily be overall buckling of the whole column. In the literature, only three test results have been previously reported for such cold-formed steel columns, and limited to values of non-dimensional slenderness ranging from 1.08 to 1.16. This issue is considered herein. The results of 40 experimental tests are reported, conducted on back-to-back gapped built-up cold-formed steel channel-sections covering the range of non-dimensional slenderness from stub to slender columns. A nonlinear finite element model is then described that shows good agreement with the experimental results. The finite element model is then used for the purposes of a study comprising 84 models. Using the experimental and finite element results, it is shown that design in accordance with the American Iron and Steel Institute (AISI) and Australian and New Zealand Standards (AS/NZS) can be conservative by as much as 53%. However, use of a modification to the non-dimensional slenderness, that considers the gap, results in the design standards being within 5% conservative with respect to the experimental and finite element results.

Large, benign intramandibular lesions are frequently removed by resection followed by extensive free tissue transfer or delayed bone grafting. We outline a protocol to remove benign mandibular lesions using sagittal split osteotomy (SSO) with virtual surgical planning (VSP) to mitigate risks involved with this effective, tissue-saving approach. Patients with benign mandibular lesions accessed by SSO with VSP during 2014 were included in this study. Computed tomographic data were imported into VSP software. Using VSP, the exact locations of mandibular lesions and the inferior alveolar nerve canal were delineated. SSO was designed virtually and provided surgeons exact measurements to gain access to lesions and to avoid vital structures intraoperatively. SSO with VSP preserved the cortical mandibular bone and the inferior alveolar neurovascular bundle in 3 patients with benign mandibular lesions. Twelve months after surgery, no patient had pathologic fracture, prolonged paresthesia (except for the patient who required inferior alveolar nerve resection), or malocclusion. No patient required bone grafting. There were no functional or aesthetic jaw deficits. SSO is an effective approach to access intramandibular lesions. The technique does not result in loss of mandibular bone, and patients return to full masticatory function compared with those who require resection and reconstruction. VSP may mitigate technical challenges associated with SSO.

Decisions regarding whether to initiate or forgo intensive care for extremely premature infants are often based on gestational age alone. However, other factors also affect the prognosis for these patients and must be taken into account. After a short review of these factors, we present the thoughts and proposals of the Risks and Pregnancy department. The proposals are to limit emergency decisions, to better take into account other factors than gestational age and prenatal predicted fetal weight in assessing the prognosis, to introduce multidisciplinary consultation in the evaluation and proposals that will be discussed with the parents, and to separate prenatal steroid therapy from decision-making regarding whether or not to administer intensive care.

A narrow maxilla with high arched palate characterizes a phenotype of obstructive sleep apnea (OSA) patients that is associated with increased nasal resistance and posterior tongue displacement. Current maxillary expansion techniques for adults are designed to correct dentofacial deformity. We describe distraction osteogenesis maxillary expansion (DOME) tailored to adult patients with OSA with narrow nasal floor and high arched palate without soft tissue redundancy. DOME is performed with placement of maxillary expanders secured by mini-implants along the midpalatal suture. This minimizes the maxillary osteotomies necessary to re-create sutural separation for reliable expansion at the nasal floor and palatal vault. We report the safety and efficacy profile of the first 20 patients at Stanford who underwent DOME.

[Figure][1] ![Figure][1] The Maseri-Florio International Lecture has become a highlight of the American College of Cardiology (ACC) Annual Scientific Session. The lecture, established by a grant from Professor Attilio Maseri, MD, FACC [ (1,2) ][2], and carrying the names of both Dr

We investigated the risk and impact of mycobacterium tuberculosis (TB) infection in patients with multiple myeloma (MM). We identified 3979 MM patients from Taiwan's National Health Insurance database between 2000 and 2011 and compared the incidence rates of TB infection in these patients with 15,916 randomly selected age-, sex-, and comorbidity-matched subjects without MM. The risk of TB was higher in the myeloma cohort (adjusted hazard ratio [HR] 3.11, 95% confidence interval [CI] 2.41-4.02). Risk factors for MM patients contracting TB were age ≥65 (adjusted HR 1.93, 95% CI 1.19-3.15), alcohol use disorder (adjusted HR 2.86, 95% CI 1.24-6.62), and steroid daily dose equivalent to prednisone 5 mg or more (adjusted HR 2.38, 95% CI 1.50-3.77). MM patients with TB had a higher mortality risk than those without (adjusted HR 2.03, 95% CI 1.54-2.67). The incidence of TB is significantly higher in MM patients.

A tapered mandibular contour is popular with Far Eastern Asians. This study describes a safe and accurate method of using preoperative virtual surgical planning (VSP) and an intraoperative ostectomy guide to maximize the esthetic outcomes of mandibular symmetry and tapering while mitigating injury to the inferior alveolar nerve (IAN). Twelve subjects with chief complaints of a wide and square lower face underwent this protocol from January to June 2015. VSP was used to confirm symmetry and preserve the IAN while maximizing the surgeon's ability to taper the lower face via mandibular inferior border ostectomy. The accuracy of this method was confirmed by superimposition of the perioperative computed tomography scans in all subjects. No subjects complained of prolonged paresthesia after 3 months. A safe and accurate protocol for achieving an esthetic lower face in indicated Far Eastern individuals is described.

Background: To evaluate the epidemiology of patients who require mechanical ventilation during hyperbaric oxygen therapy. Materials and methods: One-hundred-fifty patients who required mechanical ventilation during hyperbaric oxygen therapy were prospectively studied during a 6-year period in a French university hyperbaric centre. We analysed the indication of hyperbaric oxygen therapy, agent used for sedation, presence of a chest tube, need for vasopressor agents and tolerance and appearance of side effects. Finally, we compared the outcomes of patients according to the presence or absence of acute respiratory distress syndrome (ARDS). Results: Eleven children and 139 adult patients were included (n = 150) in the study. In both populations, carbon monoxide poisoning (51%) and iatrogenic gas embolism (33%) were the two main causes of intubation and mechanical ventilation. The combination of midazolam and sufentanil was used in 85 (67%) patients. All of the patients were given a bolus of a neuromuscular blocker during the hyperbaric session, despite the presence of ARDS in 35 patients. Patient-ventilator asynchrony was the most frequent side effect in 6 (5%) patients and was often the consequence of suboptimal sedation. Mortality was higher in the group with ARDS (23%). Conclusions: Carbon monoxide poisoning and iatrogenic gas embolism are the two main diseases of the patients who required mechanical ventilation during hyperbaric oxygen therapy in this study. Mechanical ventilation is a safe method for patients during hyperbaric oxygen therapy. Sedation needs to be perfected to avoid patient-ventilator asynchrony.

Context and aims The advent of systematic screening for rheumatic heart disease (RHD) by echocardiography in endemic regions has led to a new entity: borderline RHD. The pathogenicity and natural history of borderline RHD needs to be addressed. The aim of this study was to assess the outcomes of children detected by echocardiography as having borderline RHD. Methods Schoolchildren in 4th grade (i.e., aged 9–10years) who were prospectively echo-screened for RHD (2012–2014) in Noumea, New Caledonia, were asked to participate. Children with borderline RHD according to consistent independent review by two cardiologists were included and followed-up in 2015. Results Among the 8684 schoolchildren screened, 49 were diagnosed with borderline RHD according to the Cardiologist clinically involved in the child's management plan. After independent review by two cardiologists, 25 children were consistently diagnosed with borderline RHD and included in the follow-up study. Overall, inter-observer agreement was moderate with diagnostic kappa values of 0.63 (95% CI 0.45–0.78). After a median follow-up of 23months (IQR (20.5–33.0), 15 children (60.0%) had stability of valvular lesions, 8 (32.0%) had normal findings according to the WHF criteria. Two children (8.0%) had definite RHD on the follow-up echocardiogram, but no clinical events or audible pathological murmur during the study period. No factor could be identified as prognostic of either stability or progression. Conclusions Borderline RHD diagnosed by systematic screening in high-risk populations remains mostly unchanged at 2years follow-up. Diagnosis of borderline RHD may require two reviewers for consistency.