Lessons learnt for enhancing hospital resilience to pandemics: A qualitative analysis from Italy.

The COVID-19 pandemic has outlined the need to strengthen the resilience of healthcare systems. It has cost millions of human lives and has had indirect health impacts too. Hospital buildings have undergone extensive modifications and adaptations to ensure infection control and prevention measures, and, as it is happened following past epidemics, the COVID-19 experience might change the design of hospital buildings in the future. This paper aims to capitalise on the knowledge developed by the stakeholders directly involved with the hospital response during the pandemic to generate new evidence that will enhance resilience of hospital buildings to pandemics. The research adopted qualitative research methods, namely literature review and interviews with Italian experts including doctors and facility managers to collect data which were analysed through a thematic analysis. The findings include the identification of new needs for hospital buildings and the related actions to be taken or already performed at hospital building and service level which are viable for long term implementation and are aimed at improving hospital resilience to pandemics. The results specify how to improve resilience by means of structural modifications (e.g. placing filter zones among different wards, ensuring the presence of airborne infection isolation rooms at least in the emergency departments), technological changes (e.g. oversizing capacity such as medical gases, information technology improvement for delivering healthcare services remotely), and operational measures (e.g. assessing the risk of infection before admission, dividing acute-care from low-care assets). The needs discussed in this paper substantiate the urge to renovate the Italian healthcare infrastructures and they can be considered useful elements of knowledge for enhancing hospital resilience to pandemics in the extended and in the post-COVID-19 era.

Implementation of a strategy involving a multidisciplinary mobile unit team to prevent hospital admission in nursing home residents: protocol of a quasi-experimental study (MMU-1 study).

INTRODUCTION: Nursing home residents represent a particularly vulnerable population experiencing high risk of unplanned hospital admissions, but few interventions have proved effective in reducing this risk. The aim of this research will be to verify the effects of a hospital-based multidisciplinary mobile unit (MMU) team intervention delivering urgent care to nursing home residents directly at their bedside. METHODS AND ANALYSIS: Four nursing homes based in the Parma province, in Northern Italy, will be involved in this prospective, pragmatic, multicentre, 18-month quasiexperimental study (sequential design with two cohorts). The residents of two nursing homes will receive the MMU team care intervention. In case of urgent care needs, the nursing home physician will contact the hospital physician responsible for the MMU team by phone. The case will be triaged as (a) manageable by phone advice, (b) requiring urgent assessment by the MMU team or (c) requiring immediate emergency department (ED) referral. MMU team is composed of one senior physician and one emergency-medicine resident chosen within the staff of Internal Medicine and Critical Subacute Care Unit of Parma University-Hospital, usually with different specialty background, and equipped with portable ultrasound, set of drugs and devices useful in urgency. The MMU visits patients in nursing homes, with the mission to stabilise clinical conditions and avoid hospital admission. Residents of the other two nursing homes will receive usual care, that is, ED referral in every case of urgency. Study endpoints include unplanned hospital admissions (primary), crude all-cause mortality, hospital mortality, length of stay and healthcare-related costs (secondary). ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of Area Vasta Emilia Nord (Emilia-Romagna region). Informed consent will be collected from patients or legal representatives. The results will be actively disseminated through peer-reviewed journals and conference presentations, in compliance with the Italian law. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04085679); Pre-results.

MicroRNA-138 is a Prognostic Biomarker for Triple-Negative Breast Cancer and Promotes Tumorigenesis via TUSC2 repression.

Breast cancer manifests as a spectrum of subtypes with distinct molecular signatures, and different responses to treatment. Of these subtypes, triple-negative breast cancer (TNBC) has the worst prognoses and limited therapeutic options. Here we report aberrant expression of microRNA-138 (miR-138) in TNBC. Increased miR-138 expression is highly specific to this subtype, correlates with poor prognosis in patients, and is functionally relevant to cancer progression. Our findings establish miR-138 as a specific diagnostic and prognostic biomarker for TNBC. OncomiR-138 is pro-survival; sequence-specific miR-138 inhibition blocks proliferation, promotes apoptosis and inhibits tumour growth in-vivo. miR-138 directly targets a suite of pro-apoptotic and tumour suppressive genes, including tumour suppressor candidate 2 (TUSC2). miR-138 silences TUSC2 by binding to a unique 5'-UTR target-site, which overlaps with the translation start-site of the transcript. Over-expression of TUSC2 mimics the phenotype of miR-138 knockdown and functional rescue experiments confirm that TUSC2 is a direct downstream target of miR-138. Our report of miR-138 as an oncogenic driver in TNBC, positions it as a viable target for oligonucleotide therapeutics and we envision the potential value of using antimiR-138 as an adjuvant therapy to alleviate this therapeutically intractable cancer.

C/EBPß mediates RNA polymerase III-driven transcription of oncomiR-138 in malignant gliomas.

MicroRNA-138 (miR-138) is a pro-survival oncomiR for glioma stem cells. In malignant gliomas, dysregulated expression of microRNAs, such as miR-138, promotes Tumour initiation and progression. Here, we identify the ancillary role of the CCAAT/enhancer binding protein ß (C/EBPß) as a transcriptional activator of miR-138. We demonstrate that a short 158 bp DNA sequence encoding the precursor of miR-138-2 is essential and sufficient for transcription of miR-138. This short sequence includes the A-box and B-box elements characteristic of RNA Polymerase III (Pol III) promoters, and is also directly bound by C/EBPß via an embedded 'C/EBPß responsive element' (CRE). CRE and the Pol III B-box element overlap, suggesting that C/EBPß and transcription factor 3C (TFIIIC) interact at the miR-138-2 locus. We propose that this interaction is essential for the recruitment of the RNA Pol III initiation complex and associated transcription of the oncomiR, miR-138 in malignant gliomas.

HBN guidance sets out key principles.

With an ageing population in many countries, health and social care providers are under growing pressure to improve the quality and safety of care environments for older people, and ensure they are fit-for-purpose for caring for those with age-related conditions, including dementia. Health Building Note 08-02: Dementia-friendly health and social care environments, recently published, is the first HBN to offer specific guidance on the subject. Here Loughborough University research associates, Efthimia Pantzartzis and Federica Pascale, and Andrew Price, who is Professor of Project Management at the University, explain the background to the new HBN, and offer insights into its structure and content. June's HEJ reported on 115 Department of Health-funded pilot projects undertaken throughout England in 2013-2014 aimed at creating more 'dementia-friendly' environments in health and social care settings implemented under the DH Capital Programme, Improving the environment of care for people with dementia. The results and findings helped shape the new HBN guidance.