Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults

The burden of nosocomial SARS-CoV-2 infection remains poorly defined. We report on the outcomes of 2508 adults with molecularly-confirmed SARS-CoV-2 admitted across 18 major hospitals, representing over 60% of those hospitalised across Wales between 1 March and 1 July 2020. Inpatient mortality for nosocomial infection ranged from 38% to 42%, consistently higher than participants with community-acquired infection (31%–35%) across a range of case definitions. Those with hospital-acquired infection were older and frailer than those infected within the community. Nosocomial diagnosis occurred a median of 30 days following admission (IQR 21–63), suggesting a window for prophylactic or postexposure interventions, alongside enhanced infection control measures

Cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in progressive neurodegenerative conditions: a scoping review

BACKGROUND: Despite their potentially significant impact, cognitive disability may be overlooked in a number of progressive neurodegenerative conditions, as other difficulties dominate the clinical picture. OBJECTIVE: We examined the extent, nature and range of the research evidence relating to cognitive rehabilitation, self-management, psychotherapeutic and caregiver support interventions in Parkinsonian disorders, multiple sclerosis (MS), frontotemporal dementias (FTD), motor neuron disease and Huntington’s disease. METHODS: Scoping review based on searches of MEDLINE and CINAHL up to 15 March 2016. RESULTS: We included 140 eligible papers. Over half of the studies, and almost all the randomised controlled trials, related to MS, while a number of single case studies described interventions for people with FTD. CR interventions addressed functional ability, communication and interaction, behaviour or memory. The majority of psychotherapy interventions involved cognitive behavioural therapy for depression or anxiety. Self-management interventions were mainly available for people with MS. There were few reports of interventions specific to caregivers. Numerous methodological challenges were identified. CONCLUSIONS: The limited range of studies for all conditions except MS suggests a need firstly to synthesise systematically the available evidence across conditions and secondly to develop well-designed studies to provide evidence about the effectiveness of CR and other psychological interventions

A Framework for Implementing National Respiratory Guidelines in Wales

Introduction: Implementation outcomes are necessary to experience clinical impact of interventions in the real world. Clear synergy exists between evidence-based clinical recommendations in clinical guidelines and the evidence-based process of implementing them, however less than a quarter of clinical guidelines are implemented using a framework. Methods: Critical review and analysis of the published literature provided the basis for developing framework constructs to facilitate the process of implementing national clinical guidelines in Wales. This is an observational assessment using mixed methods to assess the acceptability and adoption of novel national clinical guidelines in Wales. The framework is adapted in preparation for formal validation. Results: A conceptual framework for implementing clinical guidelines at scale was developed from the literature and findings from thematic analysis of potential guideline adopters in Wales. This was deemed relevant to wider strategies and was therefore applied to the implementation of novel asthma/COPD and COVID-19 guidelines. Applying the framework demonstrated widespread acceptance and adoption of the guidelines across all Health Boards in NHS Wales, however evidence of widespread adherence of the guidelines with fidelity remains unproven as this requires longitudinal observation of process and clinical outcome benefits relating to each guideline recommendations. Conclusions: The differentiation of contexts between the two case studies presented here highlights the difference in pace and urgency of implementation to optimise penetration of a guideline 23 implementation strategy across a target population in Wales. It addresses much of the ambiguity of definitions and joins common principles to create a framework that can be recommended for further testing with other clinical specialities and contexts outside of Wales. Whilst the COVID-19 pandemic introduced a major barrier to guideline adoption for asthma and COPD, it also presented a unique scenario that stimulated large-scale use of a novel COVID guideline. Whilst it was too soon to explore the correlation between implementation strategies, guideline adherence, and clinical outcomes – achieving acceptance and adoption of the guidelines lays the foundations for further exploration of social benefits on a national scale

Strategies to promote guideline adoption: lessons learned from the implementation of a national COVID-19 hospital guideline across NHS Wales

There is little understanding about what proportion of the target audience have read guidelines published through the traditional approach. The COVID-19 pandemic created a particularly difficult scenario for healthcare professionals (HCP) since the evidence base rapidly changed. In response, we established a freely accessible, video-based online resource, which was formally implemented requiring user registration. The guideline rapidly gained more than 4,500 registrants in the first wave alone, including nearly 100% of respiratory, intensive care or emergency unit consultants in Wales. During the first wave, there were nearly 170,000 page views with over 31,000 video plays and an average of 5.8 visits to the site per registrant. Acceptability using an online survey showed widespread support and that the unsubscribe rates were remarkably low. We suggest that this novel approach to guideline implementation achieved its aim of widespread engagement and acceptability and serves as a potential model for future medical guidelines and education beyond COVID-19

Treadmill Exercise before and during Pregnancy Improves Bone Deficits in Pregnant Growth Restricted Rats without the Exacerbated Effects of High Fat Diet

Growth restriction programs adult bone deficits and increases the risk of obesity, which may be exacerbated during pregnancy. We aimed to determine if high-fat feeding could exacerbate the bone deficits in pregnant growth restricted dams, and whether treadmill exercise would attenuate these deficits. Uteroplacental insufficiency was induced on embryonic day 18 (E18) in Wistar Kyoto (WKY) rats using bilateral uterine vessel ligation (restricted) or sham (control) surgery. The F1 females consumed a standard or high-fat (HFD) diet from 5 weeks, commenced treadmill exercise at 16 weeks, and they were mated at 20 weeks. Femora and plasma from the pregnant dams were collected at post-mortem (E20) for peripheral quantitative computed tomography (pQCT), mechanical testing, histomorphometry, and plasma analysis. Sedentary restricted females had bone deficits compared to the controls, irrespective of diet, where such deficits were prevented with exercise. Osteocalcin increased in the sedentary restricted females compared to the control females. In the sedentary HFD females, osteocalcin was reduced and CTX-1 was increased, with increased peak force and bending stress compared to the chow females. Exercise that was initiated before and continued during pregnancy prevented bone deficits in the dams born growth restricted, whereas a HFD consumption had minimal bone effects. These findings further highlight the beneficial effects of exercise for individuals at risk of bone deficits

Association between polymorphisms of the GPX1 gene and second primary tumours after index squamous cell cancer of the head and neck.

Association between polymorphisms of the GPX1 gene and second primary tumours after index squamous cell cancer of the head and neck We investigated the association between genetic polymorphisms in GPX1 gene amongst patients who had index squamous cell carcinoma (SCCHN) and a second primary tumour (SPT) after a primary SCCHN in a case-control study. GPX1 genotypes were determined for 61 patients with SPT and for 259 control subjects by a PCR technique using a fluorescent-labelled primer. Analysis was by an ABI automated fluorescent sequencer. The associations between specific genotypes and the development of SPT were examined by logistic regression. A significant difference was found between the control group and the SPT cases in allele frequencies of GPX1 ALA*6 and ALA*7 (P-trend = 0.04). These results suggest that polymorphisms in the GPX1 gene may be a marker for SPT development and further studies are indicated. (c) 2004 Published by Elsevier Ltd

BCL10 is rarely mutated in human prostate carcinoma, small cell lung cancer, head and neck tumours, renal carcinoma and sarcomas

We have used single-strand conformation polymorphism (SSCP) analysis to screen for mutations in the BCL 10 gene in 81 primary prostate carcinomas, 20 squamous cell cancers of the head and neck, 15 small-cell lung cancer cell lines, 24 renal carcinoma cell lines and 13 sarcoma cell lines. We failed to find evidence of somatically acquired mutations of the BCL10 gene suggesting that BCL 10 does not play a major role in the development of these malignancies

Imaging Glioblastoma Metabolism by Using Hyperpolarized [1-13C]Pyruvate Demonstrates Heterogeneity in Lactate Labeling: A Proof of Principle Study.

Purpose To evaluate glioblastoma (GBM) metabolism by using hyperpolarized carbon 13 (13C) MRI to monitor the exchange of the hyperpolarized 13C label between injected [1-13C]pyruvate and tumor lactate and bicarbonate. Materials and Methods In this prospective study, seven treatment-naive patients (age [mean ± SD], 60 years ± 11; five men) with GBM were imaged at 3 T by using a dual-tuned 13C-hydrogen 1 head coil. Hyperpolarized [1-13C]pyruvate was injected, and signal was acquired by using a dynamic MRI spiral sequence. Metabolism was assessed within the tumor, in the normal-appearing brain parenchyma (NABP), and in healthy volunteers by using paired or unpaired t tests and a Wilcoxon signed rank test. The Spearman ρ correlation coefficient was used to correlate metabolite labeling with lactate dehydrogenase A (LDH-A) expression and some immunohistochemical markers. The Benjamini-Hochberg procedure was used to correct for multiple comparisons. Results The bicarbonate-to-pyruvate (BP) ratio was lower in the tumor than in the contralateral NABP (P < .01). The tumor lactate-to-pyruvate (LP) ratio was not different from that in the NABP (P = .38). The LP and BP ratios in the NABP were higher than those observed previously in healthy volunteers (P < .05). Tumor lactate and bicarbonate signal intensities were strongly correlated with the pyruvate signal intensity (ρ = 0.92, P < .001, and ρ = 0.66, P < .001, respectively), and the LP ratio was weakly correlated with LDH-A expression in biopsy samples (ρ = 0.43, P = .04). Conclusion Hyperpolarized 13C MRI demonstrated variation in lactate labeling in GBM, both within and between tumors. In contrast, bicarbonate labeling was consistently lower in tumors than in the surrounding NABP. Keywords: Hyperpolarized 13C MRI, Glioblastoma, Metabolism, Cancer, MRI, Neuro-oncology Supplemental material is available for this article. Published under a CC BY 4.0 license