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Objective: To identify predictors of 30-day survival in elderly patients with coronavirus disease 2019 (COVID-19)., Methods: Retrospective cohort study including patients with COVID-19 aged ≥65 years hospitalized in six European sites (January 2020 to May 2021). Data on demographics, comorbidities, clinical characteristics, and outcomes were collected. A predictive score (FLAMINCOV) was developed using logistic regression. Regression coefficients were used to calculate the score. External validation was performed in a cohort including elderly patients from a major COVID-19 centre in Israel. Discrimination was evaluated using the area under the receiver operating characteristic curve (AUC) in the derivation and validation cohorts. Survival risk groups based on the score were derived and applied to the validation cohort., Results: Among 3010 patients included in the derivation cohort, 30-day survival was 74.5% (2242/3010). The intensive care unit admission rate was 7.6% (228/3010). The model predicting survival included independent functional status (OR, 4.87; 95% CI, 3.93-6.03), a oxygen saturation to fraction of inspired oxygen (SpO 2 /FiO 2 ) ratio of >235 (OR, 3.75; 95% CI, 3.04-4.63), a C-reactive protein level of <14 mg/dL (OR, 2.41; 95% CI, 1.91-3.04), a creatinine level of <1.3 (OR, 2.02; 95% CI, 1.62-2.52) mg/dL, and absence of fever (OR, 1.34; 95% CI, 1.09-1.66). The score was validated in 1174 patients. The FLAMINCOV score ranges from 0 to 15 and showed good discrimination in the derivation (AUC, 0.79; 95% CI, 0.77-0.81; p < 0.001) and validation cohorts (AUC, 0.79; 95% CI, 0.76-0.81; p < 0.001). Thirty-day survival ranged from 39.4% (203/515) to 95.3% (634/665) across four risk groups according to score quartiles in the derivation cohort. Similar proportions were observed in the validation set., Discussion: The FLAMINCOV score identifying elderly with higher or lower chances of survival may allow better triage and management, including intensive care unit admission/exclusion., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Scope: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become pandemic, reaching almost one million death worldwide. At present standard treatment for coronavirus disease 2019 (COVID-19) is not well defined because the evidence, either from randomized or observational studies, with conflicting results, has led to rapid changes in treatment guidelines. Our aim was to narratively summarize the available literature on the management of COVID-19 in order to combine current evidence and interpretation of the data by experts who are treating patients in the frontline setting., Methods: The panel conducted a detailed review of the literature and eventual press releases from randomized clinical trials for each possible available treatment. Inductive PubMed search waws performed for publications relevant to the topic, including all clinical trials conducted. The result was a flowchart with treatment indications for patients with COVID-19., Implications: After 6 months of a pandemic situation and before a possible second coronavirus wave descends on Europe, it is important to evaluate which drugs proved to be effective while also considering that results from many randomized clinical trials are still awaited. Indeed, among treatments for COVID-19, only glucocorticoids have resulted in an association with a significant decrease in mortality in published randomized controlled trials. New therapeutic strategies are urgently needed., (Copyright © 2020. Published by Elsevier Ltd.)

Acute myeloid leukemia is characterized by the accumulation of clonal myeloid blast cells unable to differentiate into mature leukocytes. Chemotherapy induces remission in the majority of patients, but relapse rates are high and lead to poor clinical outcomes. Because this is primarily caused by chemotherapy-resistant leukemic stem cells (LSCs), it is essential to eradicate LSCs to improve patient survival. LSCs have predominantly been studied at the transcript level, thus information about posttranscriptionally regulated genes and associated networks is lacking. Here, we extend our previous report on LSC proteomes to healthy age-matched hematopoietic stem and progenitor cells (HSPCs) and correlate the proteomes to the corresponding transcriptomes. By comparing LSCs to leukemic blasts and healthy HSPCs, we validate candidate LSC markers and highlight novel and potentially targetable proteins that are absent or only lowly expressed in HSPCs. In addition, our data provide strong evidence that LSCs harbor a characteristic energy metabolism, adhesion molecule composition, as well as RNA-processing properties. Furthermore, correlating proteome and transcript data of the same individual samples highlights the strength of proteome analyses, which are particularly potent in detecting alterations in metabolic pathways. In summary, our study provides a comprehensive proteomic and transcriptomic characterization of functionally validated LSCs, blasts, and healthy HSPCs, representing a valuable resource helping to design LSC-directed therapies., (© 2020 by The American Society of Hematology.)

Background: Antimicrobials are among the most frequently prescribed drugs in long-term care facilities (LTCFs). Implementation of antimicrobial stewardship programmes (ASPs) is often challenging because of scarce data in this setting., Objectives: This narrative review aimed to provide data about antibiotic consumption in LTCFs and the need, implementation, and organization of ASPs in this setting., Source: PubMed was searched for studies assessing antimicrobial consumption and implementation of ASPs in LTCFs. The search was restricted to articles published in English in the last 10 years. Experts belonging to the ESCMID Study Group for Infections in the Elderly (ESGIE) reviewed the selected studies and evaluated the studies on ASPs according to the GRADE approach. Moreover, the quality of reporting has been assessed according to TREND and CONSORT checklists for quasi-experimental and cluster randomized clinical trials (cRCT), respectively., Content: Data on antibiotic consumption in LTCFs show great variability in LTCFs across and within countries. Reasons for this variability are difficult to analyse because of the differences in the types of LTCFs, their organization, and the population cared-for in the different LTCFs. However, studies show that the use of antibiotics among elderly patients in LTCFs, especially in cases of asymptomatic bacteriuria and influenza-like syndromes, is often inappropriate. High-quality cRCTs and low to moderate quality quasi-experimental studies show that educational interventions direct at nurse and physicians are effective in reducing unnecessary antibiotic prescriptions., Implications: There is an urgent need for ASPs tailored for LTCFs. Multifaceted organized educational interventions, involving both clinicians and nursing staff, should be advocated and require institutional intervention by health authorities. Future studies assessing the impact of well-defined ASPs in LTCFs should produce compelling evidence in this setting., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. All rights reserved.)

Objectives: To evaluate predictors of mortality in patients residing in nursing-homes (NHs) or long-term care facilities (LTCFs) with diagnosis of NH-acquired pneumonia (NHAP)., Methods: We conducted an observational, prospective study (December 2013-December 2015) of patients residing in nine NHs/LTCFs of Central and Northern Italy with diagnosis of NHAP. Data on demographics, comorbidities, microbiology, and therapies were entered into an electronic database. To identify risk factors associated with 30-day mortality, we performed univariable and multivariable analyses, and predictors were internally validated using a bootstrap resampling procedure. We derived a prediction rule using the coefficients obtained from the multivariable logistic regression. The model obtained was assessed using the area under the receiver operating characteristic curve (AUROC)., Results: Overall, 446 patients with NHAP were included in the final cohort. The median age was 80 (IQR 75-87) years. A definite aetiology was obtained in 120 (26.9%) patients; of these, 66 (55%) had a culture positive for a multidrug-resistant pathogen. The 30-day mortality was 28.7%. On multivariate analysis, malnutrition (OR 7.8; 95% CI 3-20.2, 2 points), bilateral pneumonia (OR 3.7; 95% CI 1.4-9.8, 1 point), acute mental status deterioration (OR 6.2; 95% CI 2.2-17.6, 2 points), hypotension (OR 7.7; 95% CI 2.3-24.9, 2 points), and PaO 2 /FiO 2 ratio ≤250 (OR 7.4; 95% CI 2.2-24.2, 2 points) were independently associated with 30-day mortality. The derived prediction rule showed an AUROC of 0.83 (95% CI 0.78-0.87, p <0.001)., Conclusions: NH residents with pneumonia have specific risk factors associated with 30-day mortality. Malnutrition and acute mental change appear as major determinants of death in this population., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate commonly used cancer websites' information provision, we developed and applied an Information Comprehensiveness Tool to breast and prostate cancer websites., Methods: We first collated questions from a systematic literature review on patient information needs. We then classified the questions in terms of spectrum of care, theme, and nature of question. "Breast cancer" and "prostate cancer" were typed into Google, and websites listed on the first page of results were selected. Two researchers, blind to each others' scores, assessed the same websites using the coding system. Each question was scored on a 3-point scale as not (0%), partially (50%) and fully (100%) answered by two researchers. Average scores were calculated across all questions. Inter-rater reliability was assessed., Results: We identified 79 general, 5 breast, and 5 prostate cancer questions. Inter-rater reliability was good, with an intraclass coefficient of 0.756 (95% CIs 0.729-0.781). 17 questions were not answered thoroughly by any website. Questions about "future planning", "monitoring", and "decision-making" were discussed least. Biomedical questions scored highest., Conclusions: More comprehensive information needs to be provided on breast and prostate cancer websites., Practice Implications: This ICT can improve cancer information online and enable patients to engage more actively regarding their information needs., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: To quantify patients' preferences for new pharmacist independent prescribing services in general practice for managing common existing long-term conditions compared with usual medical prescribing., Methods: A discrete choice experiment cross-sectional survey was conducted in five general practices in England (October-November 2009). Four service attributes reported on the length of consultation and aspects of patient-professional interaction. A choice between three alternatives-novel pharmacist independent prescribing service ("prescribing pharmacist"), "own (family) doctor" service, and "available (family) doctor" service-was presented. Alternative regression models were compared according to their goodness of fit, and the preferred one was used to inform policy analysis., Results: A total of 451 patients completed questionnaires. Respondents preferred a "pharmacist" or "own doctor" compared with "available doctor," with a larger value given to own doctor. All attributes on patient-professional interaction were important in choosing how to manage diagnosed hypertension, while the "length of consultation" (P = 0.42) did not have any impact. The impact of introducing a pharmacist prescribing service into a general practice setting was estimated from these findings. Patients' preferences suggested that about 16% of consultations with a patient's own doctor can be switched to a prescribing pharmacist instead. Although there is a stronger preference for seeing own doctor, alternative combinations of attribute levels can be used to compensate and reconfigure a more preferred prescribing pharmacist service., Conclusions: The pharmacist service is valued by patients as an alternative to doctor prescribing in primary care and therefore represents an acceptable form of service delivery when informing policy., (Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

CD4(+) cells of most individuals infected with HIV-1 harbor a C-terminally truncated and constitutively activated form of signal transducer and activator of transcription-5 (STAT5 Delta). We report that the chronically HIV-infected U1 cell line expresses STAT5 Delta but not full-length STAT5. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation of U1 cells promoted early activation of STAT5 Delta and of extracellular signal regulated kinases (ERKs), followed by later activation of activator protein 1 (AP-1) and HIV expression. Inhibition of ERK/AP-1 by PD98,059 abolished, whereas either tyrphostin AG490 or a STAT5 small interfering RNA (siRNA) enhanced, virion production in GM-CSF-stimulated U1 cells. Chromatin immunoprecipitation demonstrated the induction of STAT5 Delta binding to STAT consensus sequences in the HIV-1 promoter together with a decreased recruitment of RNA polymerase II after 1 hour of GM-CSF stimulation of U1 cells. Down-regulation of STAT5 Delta by siRNA resulted in the up-regulation of both HIV-1 gag-pol RNA and p24 Gag antigen expression in CD8-depleted leukocytes of several HIV-positive individuals cultivated ex vivo in the presence of interleukin-2 but not of interleukin-7. Thus, the constitutively activated STAT5 Delta present in the leukocytes of most HIV-positive individuals acts as a negative regulator of HIV expression.