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Abstract Background Except in a few retrospective studies mainly including patients under chemotherapy, information regarding the impact of immunosuppressive therapy on the prognosis of patients admitted to the intensive care unit (ICU) for septic shock is scarce. Accordingly, the PACIFIC study aimed to asses if immunosuppressive therapy is associated with an increased mortality in patients admitted to the ICU for septic shock. Methods This was a retrospective epidemiological multicentre study. Eight high enroller centres in septic shock randomised controlled trials (RCTs) participated in the study. Patients in the “exposed” group were selected from the screen failure logs of seven recent RCTs and excluded because of immunosuppressive treatment. The “non-exposed” patients were those included in the placebo arm of the same RCTs. A multivariate logistic regression model was used to estimate the risk of death. Results Among the 433 patients enrolled, 103 were included in the “exposed” group and 330 in the “non-exposed” group. Reason for immunosuppressive therapy included organ transplantation (n = 45 [44%]) or systemic disease (n = 58 [56%]). ICU mortality rate was 24% in the “exposed” group and 25% in the “non-exposed” group (p = 0.9). Neither in univariate nor in multivariate analysis immunosuppressive therapy was associated with a higher ICU mortality (OR: 0.95; [95% CI 0.56–1.58]: p = 0.86 and 1.13 [95% CI 0.61–2.05]: p = 0.69, respectively) or 3-month mortality (OR: 1.13; [95% CI 0.69–1.82]: p = 0.62 and OR: 1.36 [95% CI 0.78–2.37]: p = 0.28, respectively). Conclusions In this study, long-term immunosuppressive therapy excluding chemotherapy was not associated with significantly higher or lower ICU and 3-month mortality in patients admitted to the ICU for septic shock.

Abstract Background Cardiac tamponade is a rare but severe complication of pericardial effusion with a poor prognosis. Prompt diagnosis using transthoracic echocardiography allows guiding initial therapeutic management. Although etiologies are numerous, cardiac tamponade is more often due to a hemopericardium. Rarely, a coronary injury may result in such a hemopericardium with cardiac tamponade. Coronary artery aneurysm are the main etiologies but blunt, open chest trauma or complication of endovascular procedures have also been described. Case presentation A 83-year-old hypertensive man presented for dizziness and hypotension. The patient had oliguria and mottled skin. Transthoracic echocardiography disclosed a circumferential pericardial effusion with a compressed right atrium, confirmed by contrast-enhanced thoracic CT scan. A pig-tail catheter allowed to withdraw 500 mL of blood, resulting in a transient improvement of hemodynamics. Rapidly, recurrent hypotension prompted a reoperation. An active bleeding was identified at the level of the retroventricular coronary artery. The pericardium was thickened with several "sharping" calcified plaques in the vicinity of the bleeding areas. On day 2, vasopressors were stopped and the patient was successfully extubated. Final diagnosis was a spontaneous cardiac tamponade secondary to a coronary artery injury attributed to a "sharping"calcified pericardial plaque. Conclusion Cardiac tamponade secondary to the development of a hemopericardium may develop as the result of a myocardial and coronary artery injury induced by a calcified pericardial plaque.

Abstract Background The AIRE operational project will evaluate the implementation of the routine Pulse Oximeter (PO) use in the integrated management of childhood illness (IMCI) strategy for children under-5 in primary health care centers (PHC) in West Africa. The introduction of PO should promote the accurate identification of hypoxemia (pulse blood oxygen saturation Sp02

Abstract Translational research aims at reducing gaps between fundamental scientific discoveries and real-world applications. However, the trajectory of most scientific discoveries along the translation research continuum remains highly complex. Logic models are powerful tools that can help reduce this complexity. They are often used to lay out road maps and depict the relationship between activities and their intended effects. Few if any existing tools have been designed to guide the implementation and evaluation of collaborative models between community-based primary health care and biomedical research. To address this gap, we developed a logic model in two stages: 1) a literature review; and 2) the drafting and revision of the model by experts in the field. We describe its components, including objectives, inputs, activities, target groups, outputs, and results for a collaborative model involving fundamental biomedical research and primary health care practices. Our proposed logic model provides a road map that has the potential to reduce the complexity faced by translational research in chronic diseases by providing guidelines for decision-makers. Future work should attempt to validate the model before its broad-based implementation.

Abstract Background The last decade has seen growing interest in scaling up of innovations to strengthen healthcare systems. However, the lack of appropriate methods for determining their potential for scale-up is an unfortunate global handicap. Thus, we aimed to review tools proposed for assessing the scalability of innovations in health. Methods We conducted a systematic review following the COSMIN methodology. We included any empirical research which aimed to investigate the creation, validation or interpretability of a scalability assessment tool in health. We searched Embase, MEDLINE, CINAHL, Web of Science, PsycINFO, Cochrane Library and ERIC from their inception to 20 March 2019. We also searched relevant websites, screened the reference lists of relevant reports and consulted experts in the field. Two reviewers independently selected and extracted eligible reports and assessed the methodological quality of tools. We summarized data using a narrative approach involving thematic syntheses and descriptive statistics. Results We identified 31 reports describing 21 tools. Types of tools included criteria (47.6%), scales (33.3%) and checklists (19.0%). Most tools were published from 2010 onwards (90.5%), in open-access sources (85.7%) and funded by governmental or nongovernmental organizations (76.2%). All tools were in English; four were translated into French or Spanish (19.0%). Tool creation involved single (23.8%) or multiple (19.0%) types of stakeholders, or stakeholder involvement was not reported (57.1%). No studies reported involving patients or the public, or reported the sex of tool creators. Tools were created for use in high-income countries (28.6%), low- or middle-income countries (19.0%), or both (9.5%), or for transferring innovations from low- or middle-income countries to high-income countries (4.8%). Healthcare levels included public or population health (47.6%), primary healthcare (33.3%) and home care (4.8%). Most tools provided limited information on content validity (85.7%), and none reported on other measurement properties. The methodological quality of tools was deemed inadequate (61.9%) or doubtful (38.1%). Conclusions We inventoried tools for assessing the scalability of innovations in health. Existing tools are as yet of limited utility for assessing scalability in health. More work needs to be done to establish key psychometric properties of these tools. Trial registration We registered this review with PROSPERO (identifier: CRD42019107095)

Highlights Omission of sex and gender considerations is a recurring deficiency in research design and reporting Integration of sex and gender considerations in health research reporting guidelines is very low Three criteria were used to assess correct use of sex and gender concepts Only one reporting guideline met the three criteria A call to action is made to address these deficiencies

Abstract During COVID-19, immature granulocyte (IG) concentration is heterogeneous with higher concentrations than those found in bacterial sepsis. We investigated the relationship between IG levels at ICU admission and on days 7 (± 2) and 15 (± 2) and associated pulmonary bacterial infections in intensive care unit (ICU) patients hospitalized for an acute respiratory distress syndrome (ARDS) related to SARS-CoV-2. Patients with associated pulmonary bacterial infection had a peak of IGs. IG thresholds of 18% or 2 G/L allowed discriminating patients with ventilator associated pneumonia with 100% sensitivity and specificity. Our study supports that IGs could help identifying pulmonary bacterial infections in this population.

Abstract Background There is a growing interest in scaling effective health innovations to promote equitable access to high-quality health services worldwide. However, multiple challenges persist in scaling innovations. In this study, we aim to summarize the scaling evidence in the health and social care literature and identify current knowledge gaps. Methods We will conduct a living umbrella review according to the Joanna Briggs Institute Reviewers’ Manual. We will consider all knowledge syntheses addressing scaling in health or social care (e.g., any setting, any clinical area) and conducted in a systematic way. We will search the following electronic databases: MEDLINE (Ovid), Embase, PsychINFO (Ovid), CINAHL (EBSCO), Web of Science, The Cochrane Library, Sociological Abstract (Proquest), Academic Search Premier (EBSCO), and Proquest Dissertations & Theses Global, from inception. Furthermore, we will conduct searches of the grey literature. No restriction regarding date or language will be applied. Each phase of the review will be processed by two independent reviewers. We will develop a data extraction form on Covidence. We will assess the methodological quality of the included reviews using AMSTAR2 and the risk of bias using ROBIS. Results will be presented in tabular form and accompanied by a narrative synthesis covering the traditional themes of scaling science that emerge from the analysis, such as coverage, range, and sustainability, as well as themes less covered in the literature, including reporting guidance, models, tools, barriers, and/or facilitators to scaling innovations, evidence regarding application in high-income or low-income countries, and end-user engagement. We will disseminate the findings via publications and through relevant networks. Discussion The findings of the umbrella review will facilitate access to scaling evidence in the literature and help strengthen the science of scaling for researchers, policy makers, and program managers. Finally, this work will highlight important knowledge gaps and help prioritize future research questions. Systematic review registration This protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on November 11, 2020 (registration number: CRD42020183774 ).

Abstract Background Chronic pain is a common public health problem with negative consequences for individuals and societies. Fortunately, interdisciplinary chronic pain management has been shown to be effective for improving patients’ outcomes and strongly recommended in clinical practice guidelines. Appropriate referral within the healthcare system based on individuals’ needs and available services is essential to optimise health-related outcomes and maximise resources. Clinical decision support systems have been shown to be effective for supporting healthcare professionals in different practices. However, there is no knowledge synthesis on clinical decision support systems for referral within chronic pain practice. We aim to identify the clinical decision support systems for referral within chronic pain practices and assess their content, effectiveness, harms, and validation parameters. Methods Using the methodology of Cochrane reviews, we will perform a systematic review and meta-analysis based on studies meeting the following criteria: Population, patients with chronic pain and/or healthcare professionals working in chronic pain; Intervention, clinical decision support systems for referral within chronic pain practice; Comparison, any other clinical tool, any usual care or practices; Outcomes, clinical outcomes of patients measuring how patients feel, function or survive including benefits, adverse effects, continuity of care, care appropriateness, care satisfaction, quality of life, healthcare professional performance, and cost outcomes; and Study design: randomized controlled trials, non-randomized controlled trials, before and after controlled studies and interrupted time series. We will search relevant literature with the support of an information specialist using Medline, Embase, PsycInfo, CINHAL, Web of Science and Cochrane Library from their inception onwards. Two reviewers will independently complete study selection, data extraction and risk of bias assessment. We will analyse data to perform both narrative syntheses and meta-analysis if appropriate. Discussion Findings of this review will contribute to enhancing chronic pain care and research. Clinical decision support systems identified as effective in this review can be investigated for implementation in clinical practice and impact on improving patient, clinical and health system outcomes. Clinical decision support systems not yet ready for implementation that require further improvement will also be identified. Systematic review registration PROSPERO registration: CRD42020158880 .

Abstract Background The scale-up of evidence-based innovations is required to reduce waste and inequities in health and social services (HSS). However, it often tends to be a top-down process initiated by policy makers, and the values of the intended beneficiaries are forgotten. Involving multiple stakeholders including patients and the public in the scaling-up process is thus essential but highly complex. We propose to identify relevant strategies for meaningfully and equitably involving patients and the public in the science and practice of scaling up in HSS. Methods We will adapt our overall method from the RAND/UCLA Appropriateness Method. Following this, we will perform a two-prong study design (knowledge synthesis and Delphi study) grounded in an integrated knowledge translation approach. This approach involves extensive participation of a network of stakeholders interested in patient and public involvement (PPI) in scaling up and a multidisciplinary steering committee. We will conduct a systematic scoping review following the methodology recommended in the Joanna Briggs Institute Reviewers Manual. We will use the following eligibility criteria: (1) participants—any stakeholder involved in creating or testing a strategy for PPI; (2) intervention—any PPI strategy proposed for scaling-up initiatives; (3) comparator—no restriction; (4) outcomes: any process or outcome metrics related to PPI; and (5) setting—HSS. We will search electronic databases (e.g., Medline, Web of Science, Sociological Abstract) from inception onwards, hand search relevant websites, screen the reference lists of included records, and consult experts in the field. Two reviewers will independently select and extract eligible studies. We will summarize data quantitatively and qualitatively and report results using the PRISMA extension for Scoping Reviews (PRISMA-ScR) checklist. We will conduct an online Delphi survey to achieve consensus on the relevant strategies for PPI in scaling-up initiatives in HSS. Participants will include stakeholders from low-, middle-, and high-income countries. We anticipate that three rounds will allow an acceptable degree of agreement on research priorities. Discussion Our findings will advance understanding of how to meaningfully and equitably involve patients and the public in scaling-up initiatives for sustainable HSS. Systematic review registration We registered this protocol with the Open Science Framework on August 19, 2020 ( https://osf.io/zqpx7/ ).

Abstract Background Family medicine is a branch of medicine that manages common and long-term illnesses in children and adults. Family physicians in particular play a major role and their scope of practice is expected to impact patient and population. However, little is known about its impact on physicians. We aimed to assess the effects of scope of practice on family physician outcomes. Methods We performed a systematic review that we reported using PRISMA guidelines. For the inclusion criteria, any study exploring an association between the scope of practice and physician outcomes was considered. Three bibliographic databases Medline, Embase, and ERIC were consulted through OVID interface from their respective inceptions to November, 2020. Two reviewers independently selected studies, extracted data and assessed the risk of bias of studies using appropriate tools. We conducted data synthesis using a narrative form. GRADE was used for evaluating quality of cumulative evidence. Results In total, we included 12 studies with 38,732 participants from 6927 citations identified. Eleven of them were cross-sectional, and one was a cohort study with acceptable methodological quality. We found that: 1) family physicians with diverse clinical and nonclinical activities significantly improve their job satisfaction (p

Abstract Objective Incidence of right ventricular (RV) failure in septic shock patients is not well known, and tricuspid annular plane systolic excursion (TAPSE) could be of limited value. We report the incidence of RV failure in patients with septic shock, its potential impact on the response to fluids, as well as TAPSE values. Design Ancillary study of the HEMOPRED prospective multicenter study includes patients under mechanical ventilation with circulatory failure. Setting This is a multicenter intensive care unit study Patients Two hundred and eighty-two patients with septic shock were analyzed. Patients were classified in three groups based on central venous pressure (CVP) and RV size (RV/LV end-diastolic area, EDA). In group 1, patients had no RV dilatation (RV/LVEDA

Abstract Background Crystal storing histiocytosis is a rare disorder associated with monoclonal gammopathy. In this disease, monoclonal heavy and light chains accumulate in the lysosome of macrophages, leading to histiocytic reaction in different organs. It is secondary to the presence of a small B-cell clone, responsible for monoclonal immunoglobulin production. Histological diagnosis is a challenge and differential diagnoses include fibroblastic and histiocytic neoplasm. Clinical manifestations depend on the involved organs, rarely including peritoneum or digestive tract. Case presentation We present a case of a 75-year-old with a medical history of colonic carcinoma. She presented with abdominal pain and inflammatory syndrome revealing a colonic mass. Hemicolectomy was performed. Initial diagnosis was fibroblastic tumour. The patient worsened, and diagnosis of a diffuse crystal storing histiocytosis was finally done. Haematological exploration found an indolent IgG-kappa multiple myeloma. The initial treatment with conventional chemotherapy did not permit an improvement of the patient condition. Immunotherapy with anti-CD38 monoclonal antibody (daratumumab) was proposed with a clinical and biological response. Conclusion This case report emphasizes the histopathological challenge of histiocytic tumours which may involve digestive track. It focuses on the concept of monoclonal gammopathy of clinical significance, which can have a large spectrum of manifestations.

Abstract Background Lectures with slide presentations are widely used to teach evidence-based medicine to large groups. Take-home messages (THMs) are poorly identified and recollected by students. We investigated whether an instruction to list THMs in written form on slides would improve the retention thereof by residents, and the residents’ level of knowledge, 1 month after lectures. Methods Prospective blinded randomized controlled study was conducted. Twelve lectures (6 control and 6 intervention lectures) were delivered to 73 residents. For the intervention lectures, the lecturers were instructed to incorporate clear written THMs into their slide presentations. The outcomes were ability of resident to recollect THMs delivered during a lecture (as assessed by accordance rate between the lecturers’ and residents’ THMs) and knowledge (as assessed by multiple choice questions (MCQs)). Results Data for 3738 residents’ THMs and 3410 MCQs were analyzed. The intervention did not significantly increase the number of THMs written on slides (77% (n = 20/26), 95% CI 56–91 vs 64% (n = 18/28), 95% CI 44–81, p = 0.31) nor THMs retention (13% (n = 238/1791), 95% CI 12–15 vs 17% (n = 326/1947), 95% 15–18, p = 0.40) nor knowledge (63.8 ± 26.2 vs 61.1 ± 31.4 /100 points, p = 0.75). In multivariable analyses performed with all THMs written on slides from the two groups, a superior knowledge was associated with notetaking during lectures (OR 1.88, 95% CI 1.41–2.51) and THMs retention (OR 2.17, 95% CI 1.54–3.04); and THMs retention was associated with written THMs (OR 2.94, 95% CI 2.20–3.93). Conclusions In lectures delivered to residents, a third of the THMs were not in written form. An intervention based on an explicit instruction to lecturers to provide THMs in written form in their slide presentations did not result in increased use of written THMs into the slide presentation or improvement of the THMs retention or level of knowledge. However, we showed that there was a strong positive association between writing THMs on a slide, retention of THMs and residents’ knowledge. Further researches are needed to assess interventions to increase written THMs in lectures by faculty. Trial registration ClinicalTrials.gov NCT01795651 (Fev 21, 2013).

Abstract Background The literature on the implementation of knowledge products is extensive. However, this literature is still difficult to interpret for policymakers and other stakeholders when faced with choosing implementation strategies likely to bring about successful change in their health systems. This work has the particularity to examine the scope of this literature, and to clarify the effectiveness of implementation strategies for different knowledge products. Consequently, we aim to (1) determine the strengths and weaknesses of existing literature overviews; (2) produce a detailed portrait of the literature on implementation strategies for various knowledge products; and (3) assess the effectiveness of implementation strategies for each knowledge product identified and classify them. Methods We will use a three-phase approach consisting of a critical analysis of existing literature overviews, a systematic review of systematic reviews, and a series of systematic reviews and meta-analyses. We will follow the Cochrane Methodology for each of the three phases. Our eligibility criteria are defined following a PICOS approach: Population, individuals or stakeholders participating in healthcare delivery, specifically, healthcare providers, caregivers, and end users; Intervention, any type of strategy aiming to implement a knowledge product including, but not limited to, a decision support tool, a clinical practice guideline, a policy brief, or a decision-making tool, a one-pager, or a health intervention; Comparison, any comparator will be considered; Outcomes, phases 1 and 2—any outcome related to implementation strategies including, but not limited to, the measures of adherence/fidelity to the use of knowledge products, their acceptability, adoption, appropriateness, feasibility, adaptability, implementation costs, penetration/reach and sustainability; phase 3—any additional outcome related to patients (psychosocial, health behavioral, and clinical outcomes) or healthcare professionals (behavioral and performance outcomes); Setting, primary healthcare has to be covered. We will search MEDLINE (Ovid), EMBASE, Web of Science, PsycINFO, CINAHL, and the Cochrane Library from their inception onwards. For each phase, two reviewers will independently perform the selection of studies, data extraction, and assess their methodological quality. We will analyze extracted data, and perform narrative syntheses, and meta-analyses when possible. Discussion Our results could inform not only the overviews’ methodology but also the development of an online platform for the implementation strategies of knowledge products. This platform could be useful for stakeholders in implementation science. Systematic review registration Protocol registered on Open Science Framework, https://osf.io/eb8w2/ .

Abstract Background The lack of a reporting guideline for scaling of evidence-based practices (EBPs) studies has prompted the registration of the Standards for reporting studies assessing the impact of scaling strategies of EBPs (SUCCEED) with EQUATOR Network. The development of SUCCEED will be guided by the following main steps recommended for developing health research reporting guidelines. Methods Executive Committee. We established a committee composed of members of the core research team and of an advisory group. Systematic review. The protocol was registered with the Open Science Framework on 29 November 2019 (https://osf.io/vcwfx/). We will include reporting guidelines or other reports that may include items relevant to studies assessing the impact of scaling strategies. We will search the following electronic databases: EMBASE, PsycINFO, Cochrane Library, CINAHL, Web of Science, from inception. In addition, we will systematically search websites of EQUATOR and other relevant organizations. Experts in the field of reporting guidelines will also be contacted. Study selection and data extraction will be conducted independently by two reviewers. A narrative analysis will be conducted to compile a list of items for the Delphi exercise. Consensus process . We will invite panelists with expertise in: development of relevant reporting guidelines, methodologists, content experts, patient/member of the public, implementers, journal editors, and funders. We anticipated that three rounds of web-based Delphi consensus will be needed for an acceptable degree of agreement. We will use a 9-point scale (1 = extremely irrelevant to 9 = extremely relevant). Participants’ response will be categorized as irrelevant (1–3), equivocal (4–6) and relevant (7–9). For each item, the consensus is reached if at least 80% of the participants’ votes fall within the same category. The list of items from the final round will be discussed at face-to-face consensus meeting. Guideline validation . Participants will be authors of scaling studies. We will collect quantitative (questionnaire) and qualitative (semi-structured interview) data. Descriptive analyses will be conducted on quantitative data and constant comparative techniques on qualitative data. Discussion Essential items for reporting scaling studies will contribute to better reporting of scaling studies and facilitate the transparency and scaling of evidence-based health interventions.

Abstract Background According to the 2015 report of the Joint United Nations Program on Human Immunodeficiency Virus (HIV) and Acquired Immune Deficiency Syndrome (AIDS), the prevalence rates of HIV infection among men who have sex with men (MSM) varied from 6 to 37% depending on the country, far exceeding the national prevalence rates. The present study on HIV infection among men who have sex with men in sub-Saharan Africa was conducted to describe the different sampling methods used to identify this target population and compare the prevalence rates of HIV infection among MSM to that of men in the general population. Methods The selection of studies to be included was carried out in the principal electronic databases. The 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) directives were used throughout the entire process. Bias evaluation was performed using the Mixed Methods Appraisal Tool. For each country, HIV prevalence values in both groups were calculated. A prevalence ratio was also calculated to compare the prevalence rates of the two groups. Results Seventeen articles were selected. Most of the studies (82.35%) used the Respondent-Driven Sampling method. The average prevalence rate was 17.81% (range: 3.7–33.46) for MSM and 6.15% (range: 0.5–19.7) for men in the general population. Overall, the human HIV prevalence rate was 4.94 times higher among MSM than among men in the general population (95%CI: 2.91–8.37). The western and central regions of Africa, as well as low-prevalence countries (prevalence

Abstract Background Urinary tract infection (UTI) is frequently diagnosed in the Emergency Department (ED). Staphylococcus aureus (SA) is an uncommon isolate in urine cultures (0.5–6% of positive urine cultures), except in patients with risk factors for urinary tract colonization. In the absence of risk factors, community-acquired SA bacteriuria may be related to deep-seated SA infection including infective endocarditis. We hypothesized that SA bacteriuria could be a warning microbiological marker of unsuspected infective endocarditis in the ED. Methods This is a retrospective chart review of consecutive adult patients between December 2005 and February 2018. All patients admitted in the ED with both SA bacteriuria (104 CFU/ml SA isolated from a single urine sample) and SA bacteremia, without risk factors for UT colonization (i.e.,

Abstract Background While an extensive array of existing evidence-based practices (EBPs) have the potential to improve patient outcomes, little is known about how to implement EBPs on a larger scale. Therefore, we sought to identify effective strategies for scaling up EBPs in primary care. Methods We conducted a systematic review with the following inclusion criteria: (i) study design: randomized and non-randomized controlled trials, before-and-after (with/without control), and interrupted time series; (ii) participants: primary care-related units (e.g., clinical sites, patients); (iii) intervention: any strategy used to scale up an EBP; (iv) comparator: no restrictions; and (v) outcomes: no restrictions. We searched MEDLINE, Embase, PsycINFO, Web of Science, CINAHL, and the Cochrane Library from database inception to August 2016 and consulted clinical trial registries and gray literature. Two reviewers independently selected eligible studies, then extracted and analyzed data following the Cochrane methodology. We extracted components of scaling-up strategies and classified them into five categories: infrastructure, policy/regulation, financial, human resources-related, and patient involvement. We extracted scaling-up process outcomes, such as coverage, and provider/patient outcomes. We validated data extraction with study authors. Results We included 14 studies. They were published since 2003 and primarily conducted in low-/middle-income countries (n = 11). Most were funded by governmental organizations (n = 8). The clinical area most represented was infectious diseases (HIV, tuberculosis, and malaria, n = 8), followed by newborn/child care (n = 4), depression (n = 1), and preventing seniors’ falls (n = 1). Study designs were mostly before-and-after (without control, n = 8). The most frequently targeted unit of scaling up was the clinical site (n = 11). The component of a scaling-up strategy most frequently mentioned was human resource-related (n = 12). All studies reported patient/provider outcomes. Three studies reported scaling-up coverage, but no study quantitatively reported achieving a coverage of 80% in combination with a favorable impact. Conclusions We found few studies assessing strategies for scaling up EBPs in primary care settings. It is uncertain whether any strategies were effective as most studies focused more on patient/provider outcomes and less on scaling-up process outcomes. Minimal consensus on the metrics of scaling up are needed for assessing the scaling up of EBPs in primary care. Trial registration This review is registered as PROSPERO CRD42016041461 .

Abstract Background Pneumonia is a dreaded complication of varicella-zoster virus (VZV) infection in adults; however, the data are limited. Our objective was to investigate the clinical features, management, and outcomes of critically ill patients with VZV-related community-acquired pneumonia (VZV-CAP). Methods This was an observational study of patients with VZV-CAP admitted to 29 intensive care units (ICUs) from January 1996 to January 2015. Results One hundred and two patients with VZV-CAP were included. Patients were young (age 39 years (interquartile range 32–51)) and 53 (52%) were immunocompromised. Time since respiratory symptom onset was 2 (1–3) days. There was a seasonal distribution of the disease, with more cases during spring and winter time. All but four patients presented with typical skin rash on ICU admission. Half the patients received mechanical ventilation within 1 (1–2) day following ICU admission (the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) = 150 (80–284), 80% with acute respiratory distress syndrome (ARDS)). Sequential Organ Failure Assessment (SOFA) score on day 1 (odds ratio (OR) 1.90 (1.33–2.70); p

Abstract Background Endovascular interventional radiology (EIR) is an increasingly popular, mini invasive treatment option for patient with symptomatic vascular disease. The EIR practiced by qualified hands is an effective, well-tolerated procedure that offers relief of patient’s symptoms with a low risk of complications. During acute post procedural period, immediate complications may relate to vascular access, restenosis, thromboembolic events, uterine ischemia, infection, necrosis, sepsis, ICU stay, surgical recovery, pain management, treatment failure, and death. Moreover, additional non-life-threatening complications exist, but they are not well described and represent disparate information. Methods/design A range of databases will be screened consulted to identify the relevant studies: PubMed, EMBASE, The Cochrane Library, NosoBase, and Google Scholar (to identify articles not yet indexed). Scientist librarian used Medical Subject Headings (MeSH) and free terms to construct the search strategy in PubMed. This search strategy will be adapted in other databases. Two coauthors will independently select the relevant studies, extract the relevant data, and assess the risk of bias in the included studies. Any disagreements between the two authors will be solved by a third author. Discussion This systematic review will provide a synthesis of EIR complications. The spotlighted results will be analyzed in order to provide a state-of-knowledge synopsis of the current evidence base in relation to the epidemiology of the infectious complications after EIR. In the event of conclusive results, our findings will serve as a reference background to assess guidelines on reality of the problem of the infections linked to endovascular interventional radiology and to formulate of assumptions and propose preventive measures, based on the results of our investigations. These propositions will aim to reduce the risk and/or the severity of these complications in the concerned population in favor a positive medical economics report. It will also aim to decrease the antibio-resistance and in fine will improve health status and security of patients. Systematic review registration PROSPERO CRD42015025594

Abstract Acute respiratory failure (ARF) is a leading indication for performing critical care ultrasonography (CCUS) which, in these patients, combines critical care echocardiography (CCE) and chest ultrasonography. CCE is ideally suited to guide the diagnostic work-up in patients presenting with ARF since it allows the assessment of left ventricular filling pressure and pulmonary artery pressure, and the identification of a potential underlying cardiopathy. In addition, CCE precisely depicts the consequences of pulmonary vascular lesions on right ventricular function and helps in adjusting the ventilator settings in patients sustaining moderate-to-severe acute respiratory distress syndrome. Similarly, CCE helps in identifying patients at high risk of ventilator weaning failure, depicts the mechanisms of weaning pulmonary edema in those patients who fail a spontaneous breathing trial, and guides tailored therapeutic strategy. In all these clinical settings, CCE provides unparalleled information on both the efficacy and tolerance of therapeutic changes. Chest ultrasonography provides further insights into pleural and lung abnormalities associated with ARF, irrespective of its origin. It also allows the assessment of the effects of treatment on lung aeration or pleural effusions. The major limitation of lung ultrasonography is that it is currently based on a qualitative approach in the absence of standardized quantification parameters. CCE combined with chest ultrasonography rapidly provides highly relevant information in patients sustaining ARF. A pragmatic strategy based on the serial use of CCUS for the management of patients presenting with ARF of various origins is detailed in the present manuscript.

Abstract Background Expression of several copies of the heat-inducible Hsp70.1Luciferase (LUC) transgene inserted at a single X chromosome locus of a bull (Bos taurus) was assessed in females after X-chromosome inactivation (XCI). Furthermore, impact of the chromosomal environment on the spontaneous expression of these transgene copies before XCI was studied during early development in embryos obtained after in vitro fertilization (IVF), when the locus was carried by the X chromosome inherited from the bull, and after somatic cell nuclear transfer (SCNT) cloning, when the locus could be carried by the inactive Xi or the active Xa chromosome in a female donor cell, or by the (active) X in a male donor cell. Findings Transgene copies were mapped to bovine Xp22. In XXLUC female fibroblasts, i.e. after random XCI, the proportions of late-replicating inactive and early-replicating active XLUC chromosomes were not biased and the proportion of cells displaying an increase in the level of immunostained luciferase protein after heat-shock induction was similar to that in male fibroblasts. Spontaneous transgene expression occurred at the 8-16-cell stage both in transgenic (female) embryos obtained after IVF and in male and female embryos obtained after SCNT. Conclusions The XLUC chromosome is normally inactivated but at least part of the inactivated X-linked Hsp70.1Luciferase transgene copies remains heat-inducible after random XCI in somatic cells. Before XCI, the profile of the transgenes' spontaneous expression is independent of the epigenetic origin of the XLUC chromosome since it is similar in IVF female, SCNT male and SCNT female embryos.

Abstract Background The purposes of the study were to determine the relevance and validity of in vivo non-invasive radiographic assessment of the CCLT (Cranial Cruciate Ligament Transection) rabbit model of osteoarthritis (OA) and to estimate the pertinence, reliability and reproducibility of a radiographic OA (ROA) grading scale and associated radiographic atlas. Methods In vivo non-invasive extended non weight-bearing radiography of the rabbit femorotibial joint was standardized. Two hundred and fifty radiographs from control and CCLT rabbits up to five months after surgery were reviewed by three readers. They subsequently constructed an original semi-quantitative grading scale as well as an illustrative atlas of individual ROA feature for the medial compartment. To measure agreements, five readers independently scored the same radiographic sample using this atlas and three of them performed a second reading. To evaluate the pertinence of the ROA grading scale, ROA results were compared with gross examination in forty operated and ten control rabbits. Results Radiographic osteophytes of medial femoral condyles and medial tibial condyles were scored on a four point scale and dichotomously for osteophytes of medial fabella. Medial joint space width was scored as normal, reduced or absent. Each ROA features was well correlated with gross examination (p < 0.001). ICCs of each ROA features demonstrated excellent agreement between readers and within reading. Global ROA score gave the highest ICCs value for between (ICC 0.93; CI 0.90-0.96) and within (ICC ranged from 0.94 to 0.96) observer agreements. Among all individual ROA features, medial joint space width scoring gave the highest overall reliability and reproducibility and was correlated with both meniscal and cartilage macroscopic lesions (rs = 0.68 and rs = 0.58, p < 0.001 respectively). Radiographic osteophytes of the medial femoral condyle gave the lowest agreements while being well correlated with the macroscopic osteophytes (rs = 0.64, p < 0.001). Conclusion Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies.

Abstract Background Recent work has shown that mitochondrial biogenesis and mitochondrial functions are critical determinants of embryonic development. However, the expression of the factors controlling mitochondrial biogenesis in early embryogenesis has received little attention so far. Methods We used real-time quantitative PCR to quantify mitochondrial DNA (mtDNA) in bovine oocytes and in various stages of in vitro produced embryos. To investigate the molecular mechanisms responsible for the replication and the transcriptional activation of mtDNA, we quantified the mRNA corresponding to the mtDNA-encoded cytochrome oxidase 1 (COX1), and two nuclear-encoded factors, i.e. the Nuclear Respiratory Factor 1 (NRF1), and the nuclear-encoded Mitochondrial Transcription Factor A (mtTFA). Results Unlike findings reported in mouse embryos, the mtDNA content was not constant during early bovine embryogenesis. We found a sharp, 60% decrease in mtDNA content between the 2-cell and the 4/8-cell stages. COX1 mRNA was constant until the morula stage after which it increased dramatically. mtTFA mRNA was undetectable in oocytes and remained so until the 8/16-cell stage; it began to appear only at the morula stage, suggesting de novo synthesis. In contrast, NRF1 mRNA was detectable in oocytes and the quantity remained constant until the morula stage. Conclusion Our results revealed a reduction of mtDNA content in early bovine embryos suggesting an active process of mitochondrial DNA degradation. In addition, de novo mtTFA expression associated with mitochondrial biogenesis activation and high levels of NRF1 mRNA from the oocyte stage onwards argue for the essential function of these factors during the first steps of bovine embryogenesis.

Abstract Background Collaboration between biomedical research and community-based primary health care actors is essential to translate evidence into clinical practice. However, little is known about the characteristics and impacts of implementing collaborative models. Thus, we sought to identify and describe collaboration models that bridge biomedical research and community-based primary health care in chronic disease management. Methods We conducted a scoping review using Medline, Embase, Web of Science, and Cochrane Library from inception to November 2020, to identify studies describing or evaluating collaboration models. We also searched grey literature, screened reference lists, and contacted experts to retrieve further relevant references. The list of studies was then refined using more specific inclusion and exclusion criteria. Two reviewers independently selected studies and extracted relevant data (characteristics of studies, participants, collaborations, and outcomes). No bias assessment was performed. A panel of experts in the field was consulted to interpret the data. Results were presented with descriptive statistics and narrative synthesis. Results Thirteen studies presenting 20 unique collaboration models were included. These studies were conducted in North America (n = 7), Europe (n = 5) and Asia (n = 1). Collaborations were implemented between 1967 and 2014. They involved a variety of profiles including biomedical researchers (n = 20); community-based primary health care actors (n = 20); clinical researchers (n = 15); medical specialists (n = 6); and patients, citizens, or users (n = 5). The main clinical focus was cardiovascular disease (n = 8). Almost half of the collaborations operated at an international level (n = 9) and the majority adopted either a network (n = 7) or hierarchical structure (n = 6). We identified significant implementation barriers (lack of knowledge, financial support, and robust management structure) and collaboration facilitators (partnership, cooperation, multidisciplinary research teams). Out of the 20 included collaboration models, seven reported measurable impact. Conclusion We identified a large variety of collaboration models representing several clinical and research profiles and fields of expertise. As they are all based in high-income countries, further research should aim to identify collaborations in low-income countries, to determine which models and/or characteristics, could better translate evidence into clinical practice in these contexts.

Abstract Background Capnocytophaga canimorsus infection happens frequently in immunosuppressed patients with reported domestic animal bites. Clinical presentation ranges from simple cellulitis to fulminant septic shock with disseminated intravascular coagulopathy, with an overall mortality of 30%. Conventional blood culture is often negative as this is a slow-growing pathogen. Nevertheless, the increasing use of 16S rRNA gene amplification and Sanger sequencing allows a much more rapid diagnostic confirmation. We present two case reports where 16S rRNA gene sequencing helped to diagnose Capnocytophaga canimorsus infection. Case presentation Case 1: A 53-year-old man with a history of non-cirrhotic chronic alcohol consumption was admitted to the intensive care unit (ICU) for septic shock and disseminated intravascular coagulopathy (DIC) of unknown origin. Blood cultures remained negative and a 16S rRNA PCR was performed leading to the identification of Capnocytophaga Canimorsus on day 4. Targeted antibiotic therapy with ceftriaxone for 14 days lead to overall recovery. Afterwards, the patient recalled a dog bite 2 days before hospitalization with a punctiform necrotic wound localized on a finger, which was not obvious at admission. Case 2: A 38-year-old man arrived to the emergency department for acute alcohol intoxication and history of a dog bite 2 days before. At admission, septic shock with purpura fulminans was diagnosed and required ICU hospitalization, invasive mechanical ventilation, vasopressor support and renal replacement therapy due to the rapid clinical deterioration. In the context of septic shock with purpura fulminans, DIC and recent dog bite, the diagnosis of Capnocytophaga canimorsus septic shock was suspected, and early confirmed by 16S rRNA PCR coupled to Sanger sequencing on day 2. Blood cultures became only positive for Capnocytophaga canimorsus 5 days after admission. Ceftriaxone alone was infused for 10 days in total, and the patient was discharged from the ICU on day 25. Conclusions 16S rRNA gene PCR proves an important diagnostic tool when facing a sepsis of unknown origin. In these two cases of septic shock related to Capnocytophaga canimorsus, initial blood cultures remained negative at 24 h, whereas the diagnosis was achieved by 16S rRNA PCR sequencing performed from blood samples obtained at admission.

Abstract Background In the Emergency Department (ED), early and accurate recognition of infection is crucial to prompt antibiotic therapy but the initial presentation of patients is variable and poorly characterized. Lymphopenia is commonly associated with bacteraemia and poor outcome in intensive care unit patients. The objective of this retrospective study was to assess the prevalence of community-acquired infection in a cohort of unselected patients admitted to the ED with undifferentiated symptoms and severe lymphopenia. Methods This is a retrospective single-center study conducted over a 1 year-period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with severe lymphopenia (lymphocyte count

Abstract Background Mediastinitis caused by hematogenous spread of an infection is rare. We report the first known case of community-acquired mediastinitis from hematogenous origin in an immunocompetent adult. This rare invasive infection was due to Panton-Valentine Leucocidin-producing (PVL+) methicillin-susceptible Staphylococcus aureus (MSSA). Case presentation A 22-year-old obese man without other medical history was hospitalized for febrile precordial chest pain. He reported a cutaneous back abscess 3 weeks before. CT-scan was consistent with mediastinitis and blood cultures grew for a PVL+ MSSA. Intravenous clindamycin (600 mg t.i.d) and cloxacillin (2 g q.i.d.), secondary changed for fosfomycin (4 g q.i.d.) because of a related toxidermia, was administered. Surgical drainage was performed and confirmed the presence of a mediastinal abscess associated with a fistula between the mediastinum and right pleural space. All local bacteriological samples also grew for PVL+ MSSA. In addition to clindamycin, intravenous fosfomycin was switched to trimethoprim-sulfamethoxazole after 4 weeks for a total of 10 weeks of antibiotics. Conclusions We present the first community-acquired mediastinitis of hematogenous origin with PVL+ MSSA. Clinical evolution was favorable after surgical drainage and 10 weeks of antibiotics. The specific virulence of MSSA PVL+ strains played presumably a key role in this rare invasive clinical presentation.

Abstract Background When patients have been on opioid therapy for more than 90 days, more than half of them continue using opioids years later. Knowing that long-term opioid consumption could lead to harmful side effects including misuse, abuse, and addiction, it is important to understand the risks of transitioning to prolonged opioid therapy to reduce its occurrence. Perioperative and trauma contexts are ideal models commonly used to study such transition. Long-term use of opioids might be associated with transformation of acute pain to chronic, which might be an example of a risk factor. The objectives of this knowledge synthesis are to examine the relative frequency and the risk factors for transitioning to long-term opioid therapy among patients who have undergone a surgical procedure or experienced a trauma. Methods The proposed study methodology is based on Preferred ReportIng Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) statements on the conduct of systematic review and meta-analysis, the MOOSE Guidelines for Meta-Analyses and Systematic Reviews of Observational Studies, and the Cochrane Handbook for Systematic Review of Interventions. A systematic literature search will include multiple databases: Cochrane Central, EMBASE, MEDLINE, PsycINFO, CINHAL, PubMed, and the grey literature. We will identify studies related to opioid use beyond acute/subacute pain control after surgery or trauma. Two of the reviewers will screen all retrieved articles for eligibility and data extraction then critically appraise all identified studies. We will compile a narrative synthesis of all results and conduct a meta-analysis when feasible. As available data permits, we will perform a subgroup analysis of vulnerable populations. Discussion This systematic review will contribute to the prevention and harm reduction strategies associated with prescription opioids by identifying risk factors leading to the unwarranted long-term opioid therapy. The identification of common risk factors for long-term opioid therapy will help to orient further research on pain management as well as offer key therapeutic targets for the development of strategies to prevent prolonged opioid use. Systematic review registration This protocol was registered in PROSPERO on March 2, 2018; registration number CRD42012018089907.

Abstract Background Critical care is a complex field of medicine, especially because of its diversity and unpredictability. Mortality rates of the diseases are usually high and patients are critically ill, admitted in emergency, and often have several overlapping diseases. This makes research in critical care also complex because of patients’ conditions and because of the numerous ethical and regulatory requirements and increasing global competition. Many clinical trials in critical care have thus failed and almost no drug has yet been developed to treat intensive care unit (ICU) patients. Learning from the failures, clinical trials must now be optimized. Main body Several aspects can be improved, beginning with the design of studies that should take into account patients’ diversity in the ICU. At the site level, selection should reflect more accurately the potential of recruitment. Management of all players that can be involved in the research at a site level should be a priority. Moreover, training should be offered to all staff members, including the youngest. National and international networks are also part of the future as they create a collective synergy potentially improving the efficacy of sites. Finally, computerization is another area that must be further developed with the appropriate tools. Conclusion Clinical research in the ICU is thus a discipline in its own right that still requires tailored approaches. Changes have to be initiated by the investigators themselves as they know all the specificities of the field.

Background: Finger-toe pathway could represent a good alternative to assess the arterial stiffness conveniently. The aim of this study is to evaluate the accuracy of the pOpmètre which measures finger-toe pulse wave velocity (ft-PWV). Methods: The pOpmètre® has 2 photodiodes sensors, positioned on the finger and on the toe, next to the pulp artery, and a cardiac activity electrode. Pulse waves were recorded continuously for 20 sec, and the difference (Dtf) between the toe pulse wave transit times (PWtt) and the finger PWtt was calculated relative to R-ECG. The travel distance was based on subject’s height. Study 1 compared the ft-PWV to the carotid-femoral PWV (cf-PWV) obtained by the reference method SphygmoCor in 86 subjects (53±20 yrs) including 69 patients with various pathologies and 9 healthy normotensives. Study 2 compared the changes of ft-PWV and cf-PWV during a dynamic test in 10 healthy subjects. Results: ft-PWV correlated significantly with cf-PWV (r2 = 0.43, p