Management of Refractory Anaphylaxis: An Overview of Current Guidelines

Adrenaline; Anaphylaxis; VasopressorsAdrenalina; Anafilaxi; VasopressorsAdrenalina; Anafilaxia; VasopresoresIn this review, we compare different refractory anaphylaxis (RA) management guidelines focusing on cardiovascular involvement and best practice recommendations, discuss postulated pathogenic mechanisms underlining RA and highlight knowledge gaps and research priorities. There is a paucity of data supporting existing management guidelines. Therapeutic recommendations include the need for the timely administration of appropriate doses of aggressive fluid resuscitation and intravenous (IV) adrenaline in RA. The preferred second-line vasopressor (noradrenaline, vasopressin, metaraminol and dopamine) is unknown. Most guidelines recommend IV glucagon for patients on beta-blockers, despite a lack of evidence. The use of methylene blue or extracorporeal life support (ECLS) is also suggested as rescue therapy. Despite recent advances in understanding the pathogenesis of anaphylaxis, the factors that lead to a lack of response to the initial adrenaline and thus RA are unclear. Genetic factors, such as deficiency in platelet activating factor-acetyl hydrolase or hereditary alpha-tryptasaemia, mastocytosis may modulate reaction severity or response to treatment. Further research into the underlying pathophysiology of RA may help define potential new therapeutic approaches and reduce the morbidity and mortality of anaphylaxis.This work has no funding. P.J.T. is supported by the UK Medical Research Council (Grant Ref: MR/W018616/1), and through the NHR Biomedical Research Centre based at Imperial College Healthcare NHS Trust and Imperial College London. For the purpose of open access, the author has applied a Creative Commons Attribution (CC BY) license to any Author Accepted Manuscript version arising. T.E.D. is supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health, under Award Number UL1TR001425. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH

Antibiotic prescription for outpatients with influenza and subsequent hospitalisation: a cohort study using insurance data

Background Whether prophylactic administration of antibiotics to patients with influenza reduces the hospitalisation risk is unknown. We aimed to examine the association between antibiotic prescription in outpatients with influenza infection and subsequent hospitalisation. Methods We conducted a cohort study using health insurance records of Japanese clinic and hospital visits between 2012 and 2016. Participants were outpatients (age, 0–74 years) with confirmed influenza infection who were prescribed anti-influenza medicine. The primary outcomes were the hospitalisation risk from all causes and pneumonia and the duration of hospitalisation due to pneumonia. Results We analysed 903,104 outpatient records with 2469 hospitalisations. The risk of hospitalisation was greater in outpatients prescribed anti-influenza medicine plus antibiotics (0.31% for all causes and 0.18% for pneumonia) than in those prescribed anti-influenza medicine only (0.27% and 0.17%, respectively). However, the risk of hospitalisation was significantly lower in patients prescribed peramivir and antibiotics than in those prescribed peramivir only. Patients who received add-on antibiotics had a significantly longer hospital stay (4.12 days) than those who received anti-influenza medicine only (3.77 days). In all age groups, the hospitalisation risk from pneumonia tended to be greater in those who received antibiotics than in those prescribed anti-influenza medicine only. However, among older patients (65–74 years), those provided add-on antibiotics had an average 5.24-day shorter hospitalisation due to pneumonia than those provided anti-influenza medicine only (not significant). Conclusions In outpatient cases of influenza, patients who are prescribed antibiotics added to antiviral medicines have a higher risk of hospitalisation and longer duration of hospitalisation due to pneumonia

A Critical View over the Newest Antidiabetic Molecules in Light of Efficacy-A Systematic Review and Meta-Analysis

The increase in life expectancy without a decrease in the years lived without disability leads to the rise of the population aged over 65 years prone to polypharmacy. The novel antidiabetic drugs can improve this global therapeutic and health problem in patients with diabetes mellitus (DM). We aimed to establish the efficacy (A1c hemoglobin reduction) and safety of the newest antidiabetic drugs (considered so due to their novelty in medical practice use), specifically DPP-4i, SGLT-2i, GLP-1 Ra, and tirzepatide. The present meta-analysis followed the protocol registered at Prospero with the CRD42022330442 registration number. The reduction in HbA1c in the DPP4-i class for tenegliptin was 95% CI -0.54 [-1.1, 0.01], p = 0.06; in the SGLT2-iclass for ipragliflozin 95% CI -0.2 [-0.87, 0.47], p = 0.55; and for tofogliflozin 95% CI 3.13 [-12.02, 18.28], p = 0.69, while for tirzepatide it was 0.15, 95% CI [-0.50, 0.80] (p = 0.65). The guidelines for treatment in type 2 DM are provided from cardiovascular outcome trials that report mainly major adverse cardiovascular events and data about efficacy. The newest antidiabetic non-insulinic drugs are reported to be efficient in lowering HbA1c, but this effect depends between classes, molecules, or patients' age. The newest antidiabetic drugs are proven to be efficient molecules in terms of HbA1c decrease, weight reduction, and safety, but more studies are needed in order to characterize exactly their efficacy and safety profiles

Glycated hemoglobin (HbA1c) is independently associated with the bioelectrical impedance phase angle in junior sumo wrestlers: A pilot study

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Medical records as screening tools for child death review in Japan

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The social burden of antimicrobial resistance : what is it, how can we measure it, and why does it matter?

Funding: K.K. acknowledges the Holistic Approach to Unravel Antibacterial Resistance in East Africa, a Global Context Consortia Award (MR/S004785/1) funded by the National Institute for Health Research, UK Medical Research Council, and the Department of Health and Social Care, and a 3-month Visiting Professor award from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) [88887.900085/2023-00]. J.S.C. was funded by a fellowship provided by CNPQ [151272/2023-9] and FAPESP [2023/09515-5]. S.N. and C.I.R.C. are supported by British Academy [GCPS2\100009], ‘A Just Transitions framework for the equitable and sustainable mitigation of AMR’. L.S., S.N. and C.I.R.C. were supported by the Economic and Social Research Council (ESRC) [ES/P008100/1] on behalf of UK Research and Innovation (UKRI) for the Antimicrobials in Society (AMIS) grant.Antimicrobial resistance (AMR) is a growing global health threat, which is increasingly quantified in terms of its human health and economic burden. In this article, we highlight that for policy and planning purposes the social burden of AMR is as important to attend to as health and economic burdens, requiring systematic consideration and measurement of multiple dimensions. We provide a conceptual and empirical overview of four dimensions of the social burden of AMR: the distribution of AMR among and between populations; the lived experiences of AMR by patients and carers; how and by whom AMR interventions are shouldered; and how AMR can change society. We illustrate these dimensions through five case studies drawn from research projects in the UK, East Africa, Thailand and Brazil. Drawing on these insights, we discuss challenges and opportunities for documentation and measurement of AMR’s social burden going forward. Taking this seriously aligns with the consensus observation that to address AMR requires moving away from pathogen-based and siloed disciplinary perspectives and means embracing different forms of data and evidence from around the world. We propose an interdisciplinary engagement across researchers, policy makers and community stakeholders to arrive at agreed principles and metrics for future monitoring of the social burden. We need to tackle invisibility through lack of data by considering the social burden in design of AMR surveillance and research, includes mainstreaming social science data, and incorporating arts-based approaches to understanding AMR. Recognition, documentation and measurement of the social burdens of AMR will advance AMR approaches and help develop equitable solutions.Peer reviewe

Chemoprophylaxis after oncological resections

BackgroundNational societies recommend extended-duration VTE chemoprophylaxis for up to 4 weeks following major oncologic resections with the literature demonstrating an incidence of approximately 2% for symptomatic VTE. Despite this, patients are not routinely discharged on VTE chemoprophylaxis at our institution. MethodsA retrospective chart review was performed for major abdominal oncologic resections, including esophagectomy, at an academic community cancer center between 2016 and 2021. The primary outcome was the incidence of clinically evident VTE events (defined as lower extremity deep vein thrombosis (LE DVT) or pulmonary embolism (PE)) within 30 days of discharge and diagnosed on re-presentation. Exclusion criteria included in-hospital mortality, in-hospital VTE, or discharge on anti-coagulation. Comparisons were performed using Fisher’s Exact and Mann-Whitney test.ResultsAfter exclusion criteria were applied, 458 patients were identified. A total of 6 (1.3%) patients developed symptomatic VTEs, 5 (1.1%) PEs and 3 (0.7%) DVTs. No procedural interventions were required. On average, patients re-presented 14.3 (±8.4) days after discharge. There were no mortalities within 30 days of discharge. Intraoperatively, estimated blood loss in VTE group was decreased (150 vs 88 mL, p=0.01), while length of inpatient hospitalization (6.5 vs 10 days, p=0.05) was increased. Type of operation demonstrated an increased proportion of esophagectomy (9.6% vs 16.7%, p=0.57), palliative bypass (8.1% vs 33.3%, p=0.08) and small bowel resection (7.9% vs 33.3%, p=0.08) in the VTE group. Conclusion   The percentage of symptomatic VTEs in our patients was not higher then reported averages despite no patient receiving chemoprophylaxis. Questions remain as to which subset of patients would benefit from chemoprophylaxis after major abdominal oncologic resection. Further investigation into long term effects of asymptomatic DVT should be undertaken. 

Major adverse cardiovascular events (MACE) in patients with severe COVID-19 registered in the ISARIC WHO clinical characterization protocol: A prospective, multinational, observational study

COVID-19; Complications; MortalityCOVID-19; Complicacions; MortalitatCOVID-19; Complicaciones; MortalidadPurpose To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. Materials and methods This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to explore the risk factors related to MACE development and determine its impact on 28-day and 90-day mortality. Results 49,479 patients were included. Most were male 63.5% (31,441/49,479) and from high-income countries (84.4% [42,774/49,479]); however, >6000 patients were registered in low-and-middle-income countries. MACE cumulative incidence during their hospital stay was 17.8% (8829/49,479). The main risk factors independently associated with the development of MACE were older age, chronic kidney disease or cardiovascular disease, smoking history, and requirement of vasopressors or invasive mechanical ventilation at admission. The overall 28-day and 90-day mortality were higher among patients who developed MACE than those who did not (63.1% [5573/8829] vs. 35.6% [14,487/40,650] p < 0.001; 69.9% [6169/8829] vs. 37.8% [15,372/40,650] p < 0.001, respectively). After adjusting for confounders, MACE remained independently associated with higher 28-day and 90-day mortality (Odds Ratio [95% CI], 1.36 [1.33–1.39];1.47 [1.43–1.50], respectively). Conclusions Patients with severe COVID-19 frequently develop MACE, which is independently associated with worse clinical outcomes

From old indexes to new technologies

Funding Information: This work was supported by FEDER, Portugal2020, and co‐financed by Lisboa2020 and Alentejo2020 (ALT20‐03‐0247‐FEDER‐113469 and LISBOA‐01‐0247‐FEDER‐113469), ‘Fundação para a Ciência e a Tecnologia’—FCT iNOVA4Health (UIDB/Multi/04462/2020), European Commission Marie Skłodowska‐Curie Action H2020 (mtFOIE GRAS, grant agreement n. 734719) and the Sociedade Portuguesa de Diabetologia. Publisher Copyright: © 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.Background: Diabetes is a heterogeneous and multifactorial disease. However, glycemia and glycated hemoglobin have been the focus of diabetes diagnosis and management for the last decades. As diabetes management goes far beyond glucose control, it has become clear that assessment of other biochemical parameters gives a much wider view of the metabolic state of each individual, enabling a precision medicine approach. Methods: In this review, we summarize and discuss indexes that have been used in epidemiological studies and in the clinical practice. Results: Indexes of insulin secretion, sensitivity/resistance and metabolism have been developed and validated over the years to account also with insulin, C-peptide, triglycerides or even anthropometric measures. Nevertheless, each one has their own objective and consequently, advantages and disadvantages for specific cases. Thus, we discuss how new technologies, namely new sensors but also new softwares/applications, can improve the diagnosis and management of diabetes, both for healthcare professionals but also for caretakers and, importantly, to promote the empowerment of people living with diabetes. Conclusions: In long-term, the solution for a better diabetes management would be a platform that allows to integrate all sorts of relevant information for the person with diabetes and for the healthcare practitioners, namely glucose, insulin and C-peptide or, in case of need, other parameters/indexes at home, sometimes more than once a day. This solution would allow a better and simpler disease management, more adequate therapeutics thereby improving patients' quality of life and reducing associated costs.publishersversionepub_ahead_of_prin

Reduced reactive hyperemia of the brachial artery in diabetic patients assessed by repeated measurements : The FMD-J B study

Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia