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Objectives: We present the 'COVID-19 evidence ecosystem' (CEOsys) as a German network to inform pandemic management and to support clinical and public health decision-making. We discuss challenges faced when organizing the ecosystem and derive lessons learned for similar networks acting during pandemics or health-related crises., Study Design and Setting: Bringing together 18 university hospitals and additional institutions, CEOsys key activities included research prioritization, conducting living systematic reviews (LSRs), supporting evidence-based (living) guidelines, knowledge translation (KT), detecting research gaps, and deriving recommendations, backed by technical infrastructure and capacity building., Results: CEOsys rapidly produced 31 high-quality evidence syntheses and supported three living guidelines on COVID-19-related topics, while also developing methodological procedures. Challenges included CEOsys' late initiation in relation to the pandemic outbreak, the delayed prioritization of research questions, the continuously evolving COVID-19-related evidence, and establishing a technical infrastructure. Methodological-clinical tandems, the cooperation with national guideline groups and international collaborations were key for efficiency., Conclusion: CEOsys provided a proof-of-concept for a functioning evidence ecosystem at the national level. Lessons learned include that similar networks should, among others, involve methodological and clinical key stakeholders early on, aim for (inter)national collaborations, and systematically evaluate their value. We particularly call for a sustainable network., Competing Interests: Declaration of competing interest F.B. reports a relationship with Pfizer that includes: speaking and lecture fees; reports a relationship with Hans-Bockler-Foundation that includes: funding grants; reports a relationship with German Research Foundation that includes: funding grants; reports a relationship with German Federal Ministry of Health that includes: funding grants; reports a relationship with Federal German Ministry of Education and Research that includes: funding grants; reports a relationship with Charité Foundation that includes: funding grants; reports a relationship with Joint Federal Committee that includes: funding grants; reports a relationship with General Electric that includes: speaking and lecture fees; reports a relationship with Medtronic that includes: board membership. I.K. reports the following grants or contracts from any entity in the past 36 months (type of grant: third party fund; recipient: institutional): German Cancer Aid Foundation, German Ministry of Health (BMG), German Federal Joint Committee independent Funding Programme for Clinical Practice Guidelines developed under the auspices of AWMF member societies (2020-2023), German Ministry for Education and Research (BMBF; 2020-2022); reports consulting fees (recipient: personal) were provided by: European Federation of Periodontology (honoraria, travel costs; 2020-2023), British Society for Periodontology (honoraria, travel costs; 2020-2023), European Society of Endotontology (ESE; honoraria; 2021 – 2023), European Society for Contact Dermatitis (ESCD; honoraria; 2021-2021); reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (recipient: personal) by EBM Frankfurt, Working Group at the Institute for Family Medicine, Goethe-University Frankfurt (honoraria, travel costs; 2020-2022), German Society for Pediatric Infectiology (honoraria; 2021-2022), European Business School (EBS) Wiesbaden (honoraria; 2021-2022), European Association of Dental Implantologists (BDIZ; honoraria, travel costs; 2022-2022); reports payment for expert testimony was provided by German Accreditation Body (DAkkS; honoraria, travel costs); reports participation on a Data Safety Monitoring Board or Advisory Board (Agency for Quality in Medicine (ÄZQ) (a nonprofit organization)—advisory board; type of grant: honoraria, 2020-2023); reports leadership or a fiduciary role in other board, society, committee, or advocacy group (unpaid, nonfinancial): AWMF-Representative in the Board of Trustees- IQTIG (German Institute for Quality and Transparency in Health Care) a nonprofit, governmental institution), Honorary Member—German Society for Breast Health, Member—German Network for Evidence based Medicine (DNEbM), German Society of Surgery (DGCH), Member—Steering Committee for the Guideline Program in Oncology of the German Cancer Society, German Cancer Aid and AWMF, Member—Advisory Board for the Program National Disease Management Guidelines under the auspices of AWMF, German Cancer Society and AWMF, Deputy Chair- Standing Commission on Guidelines of the German Medical Association, the National Association of Statutory Health Insurance Physicians, and the AWMF, Primary Contact on behalf of the AWMF in the Guidelines International Network, Trustee, Guidelines International Network, AWMF Curriculum for guideline developers and guideline advisors; Reviewer, GIN-Mcmaster INGUIDE Program. Other financial or nonfinancial interests: Research interests (Guidelines, Health Services Research, Digitalization); and explicitly declares that she has no ties to pharmaceutical or medical product industry. M.S. reports financial support and administrative support were provided by Charité Universitätsmedizin Berlin Infectious Diseases; reports a relationship with Charité University Hospital Berlin that includes: employment. F.v.D. reports a relationship with Charité University Hospital Berlin that includes: funding grants; reports a relationship with University Medicine Greifswald that includes: funding grants. There are no competing interests for any other author., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rationale: Weaning from venovenous extracorporeal membrane oxygenation (VV-ECMO) is based on oxygenation and not on carbon dioxide elimination. Objectives: To predict readiness to wean from VV-ECMO. Methods: In this multicenter study of mechanically ventilated adults with severe acute respiratory distress syndrome receiving VV-ECMO, we investigated a variable based on CO 2 elimination. The study included a prospective interventional study of a physiological cohort ( n  = 26) and a retrospective clinical cohort ( n  = 638). Measurements and Main Results: Weaning failure in the clinical and physiological cohorts were 37% and 42%, respectively. The main cause of failure in the physiological cohort was high inspiratory effort or respiratory rate. All patients exhaled similar amounts of CO 2 , but in patients who failed the weaning trial, [Formula: see text]e was higher to maintain the Pa CO 2 unchanged. The effort to eliminate one unit-volume of CO 2 , was double in patients who failed (68.9 [42.4-123] vs. 39 [20.1-57] cm H 2 O/[L/min]; P  = 0.007), owing to the higher physiological Vd (68 [58.73] % vs. 54 [41.64] %; P  = 0.012). End-tidal partial carbon dioxide pressure (Pet CO 2 )/Pa CO 2 ratio was a clinical variable strongly associated with weaning outcome at baseline, with area under the receiver operating characteristic curve of 0.87 (95% confidence interval [CI], 0.71-1). Similarly, the Pet CO 2 /Pa CO 2 ratio was associated with weaning outcome in the clinical cohort both before the weaning trial (odds ratio, 4.14; 95% CI, 1.32-12.2; P  = 0.015) and at a sweep gas flow of zero (odds ratio, 13.1; 95% CI, 4-44.4; P  < 0.001). Conclusions: The primary reason for weaning failure from VV-ECMO is high effort to eliminate CO 2 . A higher Pet CO 2 /Pa CO 2 ratio was associated with greater likelihood of weaning from VV-ECMO.

Background: High efficacy in terms of protection from severe COVID-19 has been demonstrated for several SARS-CoV-2 vaccines. However, patients with compromised immune status develop a weaker and less stable immune response to vaccination. Strong immune response may not always translate into clinical benefit, therefore it is important to synthesise evidence on modified schemes and types of vaccination in these population subgroups for guiding health decisions. As the literature on COVID-19 vaccines continues to expand, we aimed to scope the literature on multiple subgroups to subsequently decide on the most relevant research questions to be answered by systematic reviews., Objectives: To provide an overview of the availability of existing literature on immune response and long-term clinical outcomes after COVID-19 vaccination, and to map this evidence according to the examined populations, specific vaccines, immunity parameters, and their way of determining relevant long-term outcomes and the availability of mapping between immune reactivity and relevant outcomes., Search Methods: We searched the Cochrane COVID-19 Study Register, the Web of Science Core Collection, and the World Health Organization COVID-19 Global literature on coronavirus disease on 6 December 2021.  SELECTION CRITERIA: We included studies that published results on immunity outcomes after vaccination with BNT162b2, mRNA-1273, AZD1222, Ad26.COV2.S, Sputnik V or Sputnik Light, BBIBP-CorV, or CoronaVac on predefined vulnerable subgroups such as people with malignancies, transplant recipients, people undergoing renal replacement therapy, and people with immune disorders, as well as pregnant and breastfeeding women, and children. We included studies if they had at least 100 participants (not considering healthy control groups); we excluded case studies and case series., Data Collection and Analysis: We extracted data independently and in duplicate onto an online data extraction form. Data were represented as tables and as online maps to show the frequency of studies for each item. We mapped the data according to study design, country of participant origin, patient comorbidity subgroup, intervention, outcome domains (clinical, safety, immunogenicity), and outcomes.  MAIN RESULTS: Out of 25,452 identified records, 318 studies with a total of more than 5 million participants met our eligibility criteria and were included in the review. Participants were recruited mainly from high-income countries between January 2020 and 31 October 2021 (282/318); the majority of studies included adult participants (297/318).  Haematological malignancies were the most commonly examined comorbidity group (N = 54), followed by solid tumours (N = 47), dialysis (N = 48), kidney transplant (N = 43), and rheumatic diseases (N = 28, 17, and 15 for mixed diseases, multiple sclerosis, and inflammatory bowel disease, respectively). Thirty-one studies included pregnant or breastfeeding women. The most commonly administered vaccine was BNT162b2 (N = 283), followed by mRNA-1273 (N = 153), AZD1222 (N = 66), Ad26.COV2.S (N = 42), BBIBP-CorV (N = 15), CoronaVac (N = 14), and Sputnik V (N = 5; no studies were identified for Sputnik Light). Most studies reported outcomes after regular vaccination scheme.  The majority of studies focused on immunogenicity outcomes, especially seroconversion based on binding antibody measurements and immunoglobulin G (IgG) titres (N = 179 and 175, respectively). Adverse events and serious adverse events were reported in 126 and 54 studies, whilst SARS-CoV-2 infection irrespective of severity was reported in 80 studies. Mortality due to SARS-CoV-2 infection was reported in 36 studies. Please refer to our evidence gap maps for more detailed information., Authors' Conclusions: Up to 6 December 2021, the majority of studies examined data on mRNA vaccines administered as standard vaccination schemes (two doses approximately four to eight weeks apart) that report on immunogenicity parameters or adverse events. Clinical outcomes were less commonly reported, and if so, were often reported as a secondary outcome observed in seroconversion or immunoglobulin titre studies. As informed by this scoping review, two effectiveness reviews (on haematological malignancies and kidney transplant recipients) are currently being conducted., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Acute respiratory distress syndrome (ARDS) represents the most severe course of COVID-19 (caused by the SARS-CoV-2 virus), usually resulting in a prolonged stay in an intensive care unit (ICU) and high mortality rates. Despite the fact that most affected individuals need invasive mechanical ventilation (IMV), evidence on specific ventilation strategies for ARDS caused by COVID-19 is scarce. Spontaneous breathing during IMV is part of a therapeutic concept comprising light levels of sedation and the avoidance of neuromuscular blocking agents (NMBA). This approach is potentially associated with both advantages (e.g. a preserved diaphragmatic motility and an optimised ventilation-perfusion ratio of the ventilated lung), as well as risks (e.g. a higher rate of ventilator-induced lung injury or a worsening of pulmonary oedema due to increases in transpulmonary pressure). As a consequence, spontaneous breathing in people with COVID-19-ARDS who are receiving IMV is subject to an ongoing debate amongst intensivists., Objectives: To assess the benefits and harms of early spontaneous breathing activity in invasively ventilated people with COVID-19 with ARDS compared to ventilation strategies that avoid spontaneous breathing., Search Methods: We searched the Cochrane COVID-19 Study Register (which includes CENTRAL, PubMed, Embase, Clinical Trials.gov WHO ICTRP, and medRxiv) and the WHO COVID-19 Global literature on coronavirus disease to identify completed and ongoing studies from their inception to 2 March 2022., Selection Criteria: Eligible study designs comprised randomised controlled trials (RCTs) that evaluated spontaneous breathing in participants with COVID-19-related ARDS compared to ventilation strategies that avoided spontaneous breathing (e.g. using NMBA or deep sedation levels). Additionally, we considered controlled before-after studies, interrupted time series with comparison group, prospective cohort studies and retrospective cohort studies. For these non-RCT studies, we considered a minimum total number of 50 participants to be compared as necessary for inclusion. Prioritised outcomes were all-cause mortality, clinical improvement or worsening, quality of life, rate of (serious) adverse events and rate of pneumothorax. Additional outcomes were need for tracheostomy, duration of ICU length of stay and duration of hospitalisation., Data Collection and Analysis: We followed the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Two review authors independently screened all studies at the title/abstract and full-text screening stage. We also planned to conduct data extraction and risk of bias assessment in duplicate. We planned to conduct meta-analysis for each prioritised outcome, as well as subgroup analyses of mortality regarding severity of oxygenation impairment and duration of ARDS. In addition, we planned to perform sensitivity analyses for studies at high risk of bias, studies using NMBA in addition to deep sedation level to avoid spontaneous breathing and a comparison of preprints versus peer-reviewed articles. We planned to assess the certainty of evidence using the GRADE approach., Main Results: We identified no eligible studies for this review., Authors' Conclusions: We found no direct evidence on whether early spontaneous breathing in SARS-CoV-2-induced ARDS is beneficial or detrimental to this particular group of patients.  RCTs comparing early spontaneous breathing with ventilatory strategies not allowing for spontaneous breathing in SARS-CoV-2-induced ARDS are necessary to determine its value within the treatment of severely ill people with COVID-19. Additionally, studies should aim to clarify whether treatment effects differ between people with SARS-CoV-2-induced ARDS and people with non-SARS-CoV-2-induced ARDS., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: With potential antiviral and anti-inflammatory properties, Janus kinase (JAK) inhibitors represent a potential treatment for symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. They may modulate the exuberant immune response to SARS-CoV-2 infection. Furthermore, a direct antiviral effect has been described. An understanding of the current evidence regarding the efficacy and safety of JAK inhibitors as a treatment for coronavirus disease 2019 (COVID-19) is required., Objectives: To assess the effects of systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo) on clinical outcomes in individuals (outpatient or in-hospital) with any severity of COVID-19, and to maintain the currency of the evidence using a living systematic review approach., Search Methods: We searched the Cochrane COVID-19 Study Register (comprising MEDLINE, Embase, ClinicalTrials.gov, World Health Organization (WHO) International Clinical Trials Registry Platform, medRxiv, and Cochrane Central Register of Controlled Trials), Web of Science, WHO COVID-19 Global literature on coronavirus disease, and the US Department of Veterans Affairs Evidence Synthesis Program (VA ESP) Covid-19 Evidence Reviews to identify studies up to February 2022. We monitor newly published randomised controlled trials (RCTs) weekly using the Cochrane COVID-19 Study Register, and have incorporated all new trials from this source until the first week of April 2022., Selection Criteria: We included RCTs that compared systemic JAK inhibitors plus standard of care to standard of care alone (plus/minus placebo) for the treatment of individuals with COVID-19. We used the WHO definitions of illness severity for COVID-19., Data Collection and Analysis: We assessed risk of bias of primary outcomes using Cochrane's Risk of Bias 2 (RoB 2) tool. We used GRADE to rate the certainty of evidence for the following primary outcomes: all-cause mortality (up to day 28), all-cause mortality (up to day 60), improvement in clinical status: alive and without need for in-hospital medical care (up to day 28), worsening of clinical status: new need for invasive mechanical ventilation or death (up to day 28), adverse events (any grade), serious adverse events, secondary infections., Main Results: We included six RCTs with 11,145 participants investigating systemic JAK inhibitors plus standard of care compared to standard of care alone (plus/minus placebo). Standard of care followed local protocols and included the application of glucocorticoids (five studies reported their use in a range of 70% to 95% of their participants; one study restricted glucocorticoid use to non-COVID-19 specific indications), antibiotic agents, anticoagulants, and antiviral agents, as well as non-pharmaceutical procedures. At study entry, about 65% of participants required low-flow oxygen, about 23% required high-flow oxygen or non-invasive ventilation, about 8% did not need any respiratory support, and only about 4% were intubated. We also identified 13 ongoing studies, and 9 studies that are completed or terminated and where classification is pending. Individuals with moderate to severe disease Four studies investigated the single agent baricitinib (10,815 participants), one tofacitinib (289 participants), and one ruxolitinib (41 participants). Systemic JAK inhibitors probably decrease all-cause mortality at up to day 28 (95 of 1000 participants in the intervention group versus 131 of 1000 participants in the control group; risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91; 6 studies, 11,145 participants; moderate-certainty evidence), and decrease all-cause mortality at up to day 60 (125 of 1000 participants in the intervention group versus 181 of 1000 participants in the control group; RR 0.69, 95% CI 0.56 to 0.86; 2 studies, 1626 participants; high-certainty evidence). Systemic JAK inhibitors probably make little or no difference in improvement in clinical status (discharged alive or hospitalised, but no longer requiring ongoing medical care) (801 of 1000 participants in the intervention group versus 778 of 1000 participants in the control group; RR 1.03, 95% CI 1.00 to 1.06; 4 studies, 10,802 participants; moderate-certainty evidence). They probably decrease the risk of worsening of clinical status (new need for invasive mechanical ventilation or death at day 28) (154 of 1000 participants in the intervention group versus 172 of 1000 participants in the control group; RR 0.90, 95% CI 0.82 to 0.98; 2 studies, 9417 participants; moderate-certainty evidence). Systemic JAK inhibitors probably make little or no difference in the rate of adverse events (any grade) (427 of 1000 participants in the intervention group versus 441 of 1000 participants in the control group; RR 0.97, 95% CI 0.88 to 1.08; 3 studies, 1885 participants; moderate-certainty evidence), and probably decrease the occurrence of serious adverse events (160 of 1000 participants in the intervention group versus 202 of 1000 participants in the control group; RR 0.79, 95% CI 0.68 to 0.92; 4 studies, 2901 participants; moderate-certainty evidence). JAK inhibitors may make little or no difference to the rate of secondary infection (111 of 1000 participants in the intervention group versus 113 of 1000 participants in the control group; RR 0.98, 95% CI 0.89 to 1.09; 4 studies, 10,041 participants; low-certainty evidence). Subgroup analysis by severity of COVID-19 disease or type of JAK inhibitor did not identify specific subgroups which benefit more or less from systemic JAK inhibitors. Individuals with asymptomatic or mild disease We did not identify any trial for this population., Authors' Conclusions: In hospitalised individuals with moderate to severe COVID-19, moderate-certainty evidence shows that systemic JAK inhibitors probably decrease all-cause mortality. Baricitinib was the most often evaluated JAK inhibitor. Moderate-certainty evidence suggests that they probably make little or no difference in improvement in clinical status. Moderate-certainty evidence indicates that systemic JAK inhibitors probably decrease the risk of worsening of clinical status and make little or no difference in the rate of adverse events of any grade, whilst they probably decrease the occurrence of serious adverse events. Based on low-certainty evidence, JAK inhibitors may make little or no difference in the rate of secondary infection. Subgroup analysis by severity of COVID-19 or type of agent failed to identify specific subgroups which benefit more or less from systemic JAK inhibitors. Currently, there is no evidence on the efficacy and safety of systemic JAK inhibitors for individuals with asymptomatic or mild disease (non-hospitalised individuals)., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: When the SARS-CoV-2 pandemic began, no uniform treatment and care strategies for critically ill COVID-19 patients were yet available. National and international treatment recommendations were formulated under time pressure, initially on the basis of indirect evidence from the treatment of similar diseases. In this article, we give an overview of the content, currency, and methodological quality of the existing national and international guidelines, with special attention to the care of critically ill patients., Methods: Guidelines were identified by a comprehensive search, the included guidelines were assessed in standardized fashion with the AGREE II guideline assessment instrument and according to the AMWF rulebook criteria, and the core recommendations of the included and methodologically high-quality guidelines were compared., Results: Nine of the 97 guidelines that were identified fulfilled the content criteria for inclusion, and 6 of these fulfilled the qualitative criteria; these 6 guidelines still differed, however, in the topics to which they devoted the most attention, as well as in their methodological quality and currency. The treatment strategies for patients with severe respiratory failure (lung-protective ventilation strategies and rescue measures) deviated little from established standards. Uniform recommendations were made, among other things, for the administration of dexamethasone, which was recommended in all of the guidelines for patients requiring oxygen treatment, as well as for antithrombotic drug prophylaxis and for the prone positioning of ventilated patients. Many recommendations were based on insufficient evidence, and some were contradictory, e.g., those regarding antibiotic treatment or the choice between high-flow oxygen administration via nasal canula (HFNC) and noninvasive ventilation (NIV)., Conclusion: The consultation of multiple high-quality international guidelines and guideline recommendations shared in online portals such as MagicApp are helpful sources of information for clinicians. In view of the continuing lack of strong evidence, further research on intensive care treatments is needed (aspects of ventilation, positioning therapy, and the role of extracorporeal membrane oxygenation [ECMO]).

Objective: The study objective is to evaluate the effeteness of an existing educational platform blending didactic presentation and hands-on simulation for university doctoral SRNAs in the area of basic, 4 view identification and performance of transthoracic echocardiography (TTE)., Methods: Following IRB approval, SRNAs were exposed to a pre test to evaluate existing skills, then they were exposed to a graphic rich, live presentation of basic 4 view TTE. The presentation was then followed by hands on simulation and performance of the 4 basic TTE views on live models., Results: Pretest scores averaged 58% and post tests scores rose to 95%. See Table 1., Conclusion: Our results support the concept that the existing blended platform is effective to train university SRNAs in basic 4 view, bedside transthoracic echocardiography., (© 2021. The Author(s).)

Introduction: Coronavirus disease (COVID-19) has recently dominated scientific literature. Incomplete understanding and a lack of data concerning the pathophysiology, epidemiology, and optimal treatment of the disease has resulted in conflicting recommendations. Adherence to existing guidelines and actual treatment strategies have thus far not been studied systematically. We hypothesized that capturing the variance in care would lead to the discovery of aspects that need further research and-in case of proven benefits of interventions not being performed-better communication to care providers., Methods: This article is based on a quantitative and qualitative cross-sectional mixed-methods online survey among intensive-care physicians in Germany during the COVID-19 pandemic by the CEOsys (COVID-19 Evidence Ecosystem) network, endorsed by the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI) conducted from December 3 to 31 December 2020., Results: We identified several areas of care with an especially high variance in treatment among hospitals in Germany. Crucially, 51.5% of the participating ICUs ( n = 205) reported using intubation as a last resort for respiratory failure in COVID-19 patients, while 21.8% used intubation early after admission. Furthermore, 11.5% considered extracorporeal membrane oxygenation (ECMO) in awake patients. Finally, 72.3% of respondents used the ARDS-network-table to titrate positive end-expiratory-pressure (PEEP) levels, with 36.9% choosing the low-PEEP table and 41.8% the high-PEEP table., Conclusions: We found that significant differences exist between reported treatment strategies and that adherence to published guidelines is variable. We describe necessary steps for future research based on our results highlighting significant clinical variability in care.

Background: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven., Objectives: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV., Methods: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg -1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg -1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported., Results: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone., Conclusions: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Anesthesia care increasingly includes use of regional anesthesia techniques, either as a primary anesthetic or to reduce the patient's postoperative pain. Both neuraxial anesthesia and peripheral nerve blockade have several noteworthy functions. These functions include diminishing sensory sensation to pain and potentially producing a motor blockade, both of which may facilitate the surgical procedure. The desire to reduce reliance on opioid medications, protocols to enhance and accelerate patient recovery from surgery, and patient expectations all contribute to the likelihood that use of regional anesthesia will continue to gain popularity. As such, it is essential to understand whether an association exists between regional anesthesia and adverse outcomes of care. The American Association of Nurse Anesthetists Foundation Closed Claim Research Team searched the most current database of closed claims that involved adverse outcomes when either a peripheral nerve block or a neuraxial block was a component of care in the claims. Although there were only 32 claims in the dataset, a thematic analysis resulted in the identification of 3 themes: errors in cognitive decision making, ineffective communication patterns, and production pressure., Competing Interests: The authors have declared no financial relationships with any commercial entity related to the content of this article. The authors did not discuss off label use within the article., (Copyright© by the American Association of Nurse Anesthetists.)

According to the American Society of Plastic Surgeons, there were approximately 1.8 million cosmetic and reconstructive surgeries performed in the United States in 2012. Very few anesthesia-related mortality statistics and detailed descriptions of adverse events during cosmetic/plastic surgery are found in existing literature. This article describes the use of thematic analysis, and subsequent findings, of a cosmetic closed-claim database generated by the American Association of Nurse Anesthetists (AANA) Foundation Closed Claim Research Team. From the most current dataset of 245 claim files provided by the insurance company (CNA), we isolated 25 claims regarding patients undergoing cosmetic and/or related plastic surgery procedures performed from 2003 to 2012. Three major themes emerged from the claims data: (1) normalization of deviance, (2) ineffective communication patterns, and (3) nonadherence to the AANA Standards for Nurse Anesthesia Practice. Detailed descriptions of the adverse events as they relate to the major themes are provided, and suggestions are offered for actions that may mitigate future adverse events in this subset of the population., Competing Interests: The authors have declared no financial relationships with any commercial entity related to the content of this article. The authors did not discuss off-label use within the article., (Copyright© by the American Association of Nurse Anesthetists.)

The American Association of Nurse Anesthetists (AANA) Foundation Closed Claim Research Project was initiated in 1995 and remains active to date. The charge accepted by the Closed Claim Research Team is to conduct comprehensive analyses of adverse anesthesia outcomes from medical malpractice claims, identify causes of anesthesia patient injury and negative patient outcome trends, provide data that can be used to facilitate nurse anesthesia educational curricula, and facilitate recommendations for AANA practice standards. The overall goal of closed-claim research is to improve patient safety., Competing Interests: The author has declared no financial relationships with any commercial entity related to the content of this article. The author did not discuss offlabel use within the article., (Copyright© by the American Association of Nurse Anesthetists.)

Background: While most Direct laryngoscopy leads to dental injury in 25-39% of cases. Dental injury occurs when the forces and impacts applied to the teeth exceed the ability of the structures to dissipate energy and stress. The purpose of this study was to measure strain, (which is the change produced in the length of the tooth by a force applied to the tooth) strain rate, and strain-time integral to the maxillary incisors and determine if they varied by experience, type of blade, or use of an alcohol protective pad (APP)., Methods: A mannequin head designed to teach and test intubation was instrumented with eight single axis strain gauges placed on the four maxillary incisors: four on the facial or front surface of the incisors and four on the lingual or back, near the insertion of the incisor in the gums to measure bending strain as well as compression. Anesthesiology faculty, residents, and certified registered nurse anesthetists intubated with Macintosh and Miller blades with and without APP. Using strain-time curves, the maximum strain, strain rate, and strain time integral were calculated., Results: Across the 92 subjects, strain varied 8-12 fold between the 25th and 75th percentiles for all four techniques, but little by experience, while strain rate and strain integral varied 6-13 fold and 15-26 fold, respectively, for the same percentiles. Intubators who had high strain values with one blade tended to have high strains with the other blade with and without the APP (all pairwise correlation rho = 0.42-0.63)., Conclusions: Strain varies widely by intubator and that the use of the APP reduces strain rate which may decrease the risk of or the severity of dental injury.

In the context of pandemic influenza, the prompt and effective implementation of control measures is of great concern for public health officials around the world. In particular, the role of vaccination should be considered as part of any pandemic preparedness plan. The timely production and efficient distribution of pandemic influenza vaccines are important factors to consider in mitigating the morbidity and mortality impact of an influenza pandemic, particularly for those individuals at highest risk of developing severe disease. In this paper, we use a mathematical model that incorporates age-structured transmission dynamics of influenza to evaluate optimal vaccination strategies in the epidemiological context of the Spring 2009 A (H1N1) pandemic in Mexico. We extend previous work on age-specific vaccination strategies to time-dependent optimal vaccination policies by solving an optimal control problem with the aim of minimizing the number of infected individuals over the course of a single pandemic wave. Optimal vaccination policies are computed and analyzed under different vaccination coverages (21%-77%) and different transmissibility levels ([Formula: see text] in the range of 1.8-3). The results suggest that the optimal vaccination can be achieved by allocating most vaccines to young adults (20-39 yr) followed by school age children (6-12 yr) when the vaccination coverage does not exceed 30%. For higher [Formula: see text] levels ([Formula: see text]), or a time delay in the implementation of vaccination (>90 days), a quick and substantial decrease in the pool of susceptibles would require the implementation of an intensive vaccination protocol within a shorter period of time. Our results indicate that optimal age-specific vaccination rates are significantly associated with [Formula: see text], the amount of vaccines available and the timing of vaccination.

Background: Early treatment with rt-PA is critical for favorable outcome of acute stroke. However, only a very small proportion of stroke patients receive this treatment, as most arrive at hospital too late to be eligible for rt-PA therapy., Methods and Findings: We developed a "Mobile Stroke Unit", consisting of an ambulance equipped with computed tomography, a point-of-care laboratory system for complete stroke laboratory work-up, and telemedicine capabilities for contact with hospital experts, to achieve delivery of etiology-specific and guideline-adherent stroke treatment at the site of the emergency, well before arrival at the hospital. In a departure from current practice, stroke patients could be differentially treated according to their ischemic or hemorrhagic etiology even in the prehospital phase of stroke management. Immediate diagnosis of cerebral ischemia and exclusion of thrombolysis contraindications enabled us to perform prehospital rt-PA thrombolysis as bridging to later intra-arterial recanalization in one patient. In a complementary patient with cerebral hemorrhage, prehospital diagnosis allowed immediate initiation of hemorrhage-specific blood pressure management and telemedicine consultation regarding surgery. Call-to-therapy-decision times were 35 minutes., Conclusion: This preliminary study proves the feasibility of guideline-adherent, etiology-specific and causal treatment of acute stroke directly at the emergency site.

CNS infections caused by infective agents are rare in immunocompetent hosts, but more frequent in immunocompromised patients. In addition, the spectrum of causative agents is completely different. There are no pathognomonic alterations in radiologic imaging, even in clinically severely ill patients imaging is often non-specific or inconspicious. This article gives a review of the most frequent infective agents and image alterations. Modern radiology is not yet able to replace the gold standard of pathogen detection.