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British Rhinological Society Consensus Guidance on the use of biological therapies for Chronic Rhinosinusitis with Nasal Polyps.
No full textOBJECTIVES
We set out to create Consensus Guidelines, based on current evidence and relative risks of adverse effects and the costs of different treatments, that reflect the views of the British Rhinological Society (BRS) Council on where the use of biologics should be positioned within treatment pathways for CRSwNP, specifically in the setting of the National Health Service (NHS).
DESIGN
An expert panel of 16 members was assembled. A review of the literature and evidence synthesis was undertaken and circulated to the panel We used the RAND/UCLA methodology with a multi-step process to make recommendations on the use of biologics.
SETTING
N/A PARTICIPANTS: N/A RESULTS: Recommendations were made, based on underlying disease severity, prior treatments and co-morbidities. A group of patients for whom biologics were considered an appropriate treatment option for CRSwNP was defined.
CONCLUSIONS
Although biologics are not currently available for the treatment of CRSwNP, the BRS Council have defined a group of patients who have higher rates of 'failure' with current treatment pathways, higher resource use and are more likely to suffer with uncontrolled symptoms. We would urge NICE to consider approval of biologics for such indications without applying further restrictions on use
The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells.
No full textCancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways
Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial.
No full textBACKGROUND
A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant.
METHODS
Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 - relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137.
FINDINGS
Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18-55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2-11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6-84·5) for B.1.1.7 and 81·5% (67·9-89·4) for non-B.1.1.7 lineages.
INTERPRETATION
ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2.
FUNDING
UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca
Allergic Disease Prevalence in School Children in Bengaluru, India: A Cross-Sectional Survey.
No full textIndia is a Low-Middle Income Country (LMIC) with a population of ~1.3bn. It is the second most populous country comprising 20% of the global population. Whilst India has not faced an 'allergy epidemic' as in High Income Countries (HICs), there is some evidence that the burden of allergic diseases has gradually risen1, and is greatly magnified by the absolute numbers and is compounded by the unmet demand for allergy services2,3. Data regarding epidemiology, risk factors and natural course of allergic diseases in India are relatively sparse. By virtue of considerable diversity in culture, breast feeding, infections including parasitic, diet, environmental conditions such as weather, aero-allergens, and unacceptably high levels of particulate matter ≤2.5µm (PM ), India offers an invaluable platform to study immune-mediated diseases
Racial disparity in curative treatment and survival from solid-organ cancers.
No full textRace is an important prognostic factor affecting allocation to intervention and survival from cancer treatment in the USA. The mechanism of this association is an important area for future investigation
Quality and Completeness of Myocardial Infarction Recording in Clinical Practice Research Datalink Aurum.
No full textBackground
Validation studies of the Clinical Practice Research Datalink (CPRD) Aurum database in the UK are critical for making decisions about its suitability and validity for research purposes.
Objective
To examine data source agreement of myocardial infarction (MI) diagnoses recorded in CPRD Aurum compared with linked Hospital Episode Statistics (HES) data. This comparison provides information on CPRD Aurum data correctness (accuracy, validity) and completeness (presence, missingness).
Methods
Patients with MI diagnoses recorded in either data source were selected from a random sample of 50,000 patients in CPRD Aurum with HES linkage (1997-2017). Correctness was defined as the proportion of MI cases in CPRD Aurum with a concordant MI diagnosis recorded in HES or with strong supporting evidence in either data source. Completeness was defined as the proportion of patients with primary HES-coded MIs with strong supporting evidence that were also present in CPRD Aurum.
Results
There were 1260 patients with MI recorded in the CPRD Aurum sample. The overall correctness of the recorded MI diagnoses was 94%: 986 patients (78%) had concordant diagnoses in HES within 90 days; 123 (10%) were concordant with HES, but with an inconclusive date and another 71 (6%) had strong supporting evidence for being a true MI case. There were 1125 patients with MI recorded in HES primary diagnosis fields with strong supporting evidence in either data source. Of these, 880 (78%) were present in CPRD Aurum, with completeness somewhat higher in more recent years.
Conclusion
MI diagnoses recorded in CPRD Aurum were highly likely to be correct, supporting its use in clinical research studies. Completeness was lower, indicating the need for data linkage for some studies
Reporting guidelines for artificial intelligence in healthcare research.
No full textReporting guidelines are structured tools developed using explicit methodology that specify the minimum information required by researchers when reporting a study. The use of artificial intelligence (AI) reporting guidelines that address potential sources of bias specific to studies involving AI interventions has the potential to improve the quality of AI studies, through improvements in their design and delivery, and the completeness and transparency of their reporting. With a number of guidance documents relating to AI studies emerging from different specialist societies, this Review article provides researchers with some key principles for selecting the most appropriate reporting guidelines for a study involving an AI intervention. As the main determinants of a high-quality study are contained within the methodology of the study design rather than the intervention, researchers are recommended to use reporting guidelines that are specific to the study design, and then supplement them with AI-specific guidance contained within available AI reporting guidelines
Brain injury after cardiac arrest.
No full textAs more people are surviving cardiac arrest, focus needs to shift towards improving neurological outcomes and quality of life in survivors. Brain injury after resuscitation, a common sequela following cardiac arrest, ranges in severity from mild impairment to devastating brain injury and brainstem death. Effective strategies to minimise brain injury after resuscitation include early intervention with cardiopulmonary resuscitation and defibrillation, restoration of normal physiology, and targeted temperature management. It is important to identify people who might have a poor outcome, to enable informed choices about continuation or withdrawal of life-sustaining treatments. Multimodal prediction guidelines seek to avoid premature withdrawal in those who might survive with a good neurological outcome, or prolonging treatment that might result in survival with severe disability. Approximately one in three admitted to intensive care will survive, many of whom will need intensive, tailored rehabilitation after discharge to have the best outcomes
Drug-Related Problems in Hospitalised Patients with Chronic Kidney Disease: A Systematic Review.
No full textINTRODUCTION
Globally, chronic kidney disease (CKD) is one of the leading causes of mortality. Impaired renal function makes CKD patients vulnerable to drug-related problems (DRPs).
AIM
The aim of this systematic review was to investigate the prevalence and nature of DRPs among hospital in-patients with CKD.
METHODS
A systematic review of the literature was conducted using Medline, EMBASE, PsycINFO, Web of Science (Core Collection), CINAHL plus (EBSCO), Cochrane Library (Wiley), Scopus (ELSEVIER) and PubMed (U.S.NLM) from index inception to January 2020. Studies investigating DRPs in hospitalised CKD patients published in the English language were included. Two independent reviewers extracted the data and undertook quality assessment using the Joanna Briggs Institute (JBI) tool.
RESULTS
A total of 2895 unique titles were identified; with 20 meeting the inclusion criteria. DRPs prevalence in CKD was reported between 12 and 87%. The most common DRPs included ineffective treatment, inappropriate drug choice and dosing problems. Antibiotics, H2-antihistamines and oral antidiabetics (metformin) were common drug classes involved in DRPs. Factors associated with DRPs included severity of CKD, the number of medications taken, age, length of hospital stay, and gender.
CONCLUSION
This systematic review provides evidence that DRPs are a frequent occurrence and burden for hospitalised patients with stage 1-4 CKD. Heterogeneity in study design, case detection and definitions are common, and future studies should use clearer definitions and study designs. Protocol Registration: PROSPERO: CRD42018096364