Pseudomonas aeruginosa, a Gram-negative bacterium, is one of the most common pathogens colonizing the lungs of cystic fibrosis patients. P. aeruginosa secrete extracellular vesicles (EVs) that contain LPS and other virulence factors that modulate the host’s innate immune response, leading to an increased local proinflammatory response and reduced pathogen clearance, resulting in chronic infection and ultimately poor patient outcomes. Lung macrophages are the first line of defense in the airway innate immune response to pathogens. Proper host response to bacterial infection requires communication between APC and T cells, ultimately leading to pathogen clearance. In this study, we investigate whether EVs secreted from P. aeruginosa alter MHC Ag expression in lung macrophages, thereby potentially contributing to decreased pathogen clearance. Primary lung macrophages from human subjects were collected via bronchoalveolar lavage and exposed to EVs isolated from P. aeruginosa in vitro. Gene expression was measured with the NanoString nCounter gene expression assay. DNA methylation was measured with the EPIC array platform to assess changes in methylation. P. aeruginosa EVs suppress the expression of 11 different MHC-associated molecules in lung macrophages. Additionally, we show reduced DNA methylation in a regulatory region of gene complement factor B (CFB) as the possible driving mechanism of widespread MHC gene suppression. Our results demonstrate MHC molecule downregulation by P. aeruginosa-derived EVs in lung macrophages, which is consistent with an immune evasion strategy employed by a prokaryote in a host-pathogen interaction, potentially leading to decreased pulmonary bacterial clearance.

The coronavirus disease 2019 (COVID-19) outbreak increases the importance of strategies to enhance urgent medical care delivery in long-term care (LTC) facilities that could potentially reduce transfers to emergency departments. The study objective was to model resource requirements to deliver virtual urgent medical care in LTC facilities.

We used data from all general medicine inpatient admissions at 7 hospitals in the Greater Toronto Area, Ontario, Canada, over a 7.5-year period (Apr. 1, 2010, to Oct. 31, 2017) to estimate historical patterns of hospital resource use by LTC residents. We estimated an upper bound of potentially avoidable transfers by combining data on short admissions (≤ 72 h) with historical data on the proportion of transfers from LTC facilities for which patients were discharged from the emergency department without admission. Regression models were used to extrapolate future resource requirements, and queuing models were used to estimate physician staffing requirements to perform virans would provide services similar in efficiency (measured by waiting time for physician assessment) to 7 separate centres staffed by 1 physician each.

The provision of acute medical care to LTC residents at their facility would probably require rapid access to outpatient diagnostic imaging, within-facility access to laboratory services and intravenous medication and virtual consultations with physicians. The results of this study can inform efforts to deliver urgent medical care in LTC facilities in light of a potential surge in COVID-19 cases.

The provision of acute medical care to LTC residents at their facility would probably require rapid access to outpatient diagnostic imaging, within-facility access to laboratory services and intravenous medication and virtual consultations with physicians. The results of this study can inform efforts to deliver urgent medical care in LTC facilities in light of a potential surge in COVID-19 cases.Most antiviral or immunomodulatory therapies investigated for use in patients with COVID-19 have failed to show any mortality benefit. Similar to the previous pandemics caused by respiratory viruses, the role and benefit of corticosteroids has been under debate in COVID-19-related pulmonary disease. In this consult, we discuss the evidence regarding the efficacy of corticosteroid use in hospitalized patients with COVID-19, including data from the first randomized controlled trial on this subject.

Self-management and remaining physically active are first-line recommendations for the care of patients with low back pain (LBP). With a lifetime prevalence of up to 85%, novel approaches to support behavioural self-management are needed. Internet interventions may provide accessible support for self-management of LBP in primary care. The aim of this randomised controlled trial is to determine the clinical and cost-effectiveness of the 'SupportBack’ internet intervention, with or without physiotherapist telephone support in reducing LBP-related disability in primary care patients.

A three-parallel arm, multicentre randomised controlled trial will compare three arms (1) usual primary care for LBP; (2) usual primary care for LBP and an internet intervention; (3) usual primary care for LBP and an internet intervention with additional physiotherapist telephone support. Patients with current LBP and no indicators of serious spinal pathology are identified and invited via general practice list searches and mailour full dissemination strategy.

ISRCTN14736486.

ISRCTN14736486.

Neonatal sepsis is responsible for significant morbidity and mortality worldwide. Diagnosis is often difficult due to non-specific clinical features and the unavailability of laboratory tests in many low-income and middle-income countries (LMICs). Clinical prediction models have the potential to improve diagnostic accuracy and rationalise antibiotic usage in neonatal units, which may result in reduced antimicrobial resistance and improved neonatal outcomes. In this paper, we outline our scoping review protocol to map the literature concerning clinical prediction models to diagnose neonatal sepsis. We aim to provide an overview of existing models and evidence underlying their use and compare prediction models between high-income countries and LMICs.

The protocol was developed with reference to recommendations by the Joanna Briggs Institute. Searches will include six electronic databases (Ovid MEDLINE, Ovid Embase, Scopus, Web of Science, Global Index Medicus and the Cochrane Library) supplemented by hand searching of reference lists and citation analysis on included studies. No time period restrictions will be applied but only studies published in English or Spanish will be included. Screening and data extraction will be performed independently by two reviewers, with a third reviewer used to resolve conflicts. The results will be reported by narrative synthesis in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines.

The nature of the scoping review methodology means that this study does not require ethical approval. Results will be disseminated through peer-reviewed publications and conference presentations, as well as through engagement with peers and relevant stakeholders.

The nature of the scoping review methodology means that this study does not require ethical approval. Results will be disseminated through peer-reviewed publications and conference presentations, as well as through engagement with peers and relevant stakeholders.

Polypharmacy occurs in approximately 30% of older adults aged 65 years or more, particularly among those with multimorbidity. With polypharmacy, there is an associated risk of potentially inappropriate prescribing (PIP). The aims of this scoping review were to (1) identify the intervention elements that have been adopted to reduce PIP in the outpatient setting and (2) determine the behaviour change wheel (BCW) intervention functions performed by each of the identified intervention elements.

Scoping review DATA SOURCES PubMed, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Web of Science and Cochrane Library databases, grey literature sources, six key geriatrics journals and the reference lists of review papers.

All studies reporting an intervention or strategy that addressed PIP in the older adult population (age ≥65) with multimorbidity in the outpatient setting and in which the primary prescriber is the physician.

Data extracted from the included studies can be broadly categorisedons that aim to reduce PIP.

PIP is a multifaceted problem that involves multiple stakeholders. As such, interventions that address PIP require multiple elements to target the behaviour of the various stakeholders. The intervention elements and their corresponding functions identified in this scoping review will serve to inform the design of complex interventions that aim to reduce PIP.

Migraine has consistently been connected with rosacea. Commonalities in epidemiology, trigger factors and associated neuropeptides support shared aetiology and pathophysiological pathways, though underlying mechanisms remain unclear. We established two cohorts of patients diagnosed with either migraine and/or rosacea. All patients were phenotyped in regard to migraine and rosacea. In this article, we describe the baseline parameters of the cohorts. In the future, we expect that these cohorts will help uncover potential disease overlaps and allow for prolonged follow-up through national Danish health registers.

COpenhagen ROsacea COhort (COROCO) and COpenhagen MIgraine COhort (COMICO) are prospective cohorts based in the Capital region of Denmark. Participants for COROCO were recruited primarily through two tertiary dermatology clinics in Copenhagen, Denmark and patients for COMICO were recruited through a tertiary neurology clinic in Copenhagen, Denmark.

COROCO 67.7% women (median age 51 years (interquartile range (IQR) 43.0-61.0)). Family history of migraine 44.3%. Family history of rosacea 45%. There were 13% who currently smoked, and 36.6% were former smokers. Regular intake of alcohol was present in 79.3% (median 4 items/week (IQR 1.0-9.0)). Median body mass index (BMI) 25.7 (IQR 23.1-29.0). Median Dermatology Life Quality Index (DLQI) 2 (IQR 1-5).

88.5% women (median age 41 years (IQR 29.5-51.0)). Family history of migraine 73.4%. Family history of rosacea 18.4%. There were 17.1% who currently smoked, and 26.0% former smokers. Regular intake of alcohol was present in 62.2% (median intake 2 item/week (IQR 1.0-3.0)). Median BMI was 24.6 (IQR 21.5-28.2). Median DLQI was 1 (IQR 0-2).

COROCO and COMICO serve as strong data sources that will be used for future studies on rosacea and migraine with focus on risk factors, occurrence, treatment, natural history, complications, comorbidities and prognosis.

ClinicalTrials.gov Registry (NCT03872050).

ClinicalTrials.gov Registry (NCT03872050).

Intracerebral haemorrhage (ICH) is a life-threatening condition with no effective internal treatment options. However, edaravone is a promising therapeutic agent, although its beneficial effects are inconclusive based on previous systematic reviews and meta-analyses. While several trials in the last 8 years have reported the favourable long-term functional outcomes, a few reports indicated edaravone to be associated with an increase in adverse events.

This protocol was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will perform the comprehensive and manual search for published articles, ongoing trials, dissertations and grey literature. The following databases will be searched from inception to 23 April 2020 Medline, Embase, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Chinese scientific periodical database of VIP INFORMATION, Wanfang Data and SinoMed, with no language restrictions. All randomised controlled trials that (1) compared edaravone with placebo or no treatment, and (2) compared edaravone plus routine treatment or cointervention with routine treatment or cointervention for treating acute ICH will be included.