Abstract
Background
Without inclusion of diverse research participants, it is challenging to understand how study findings will translate into the real world. Despite this, a lack of inclusion of ...those from under-served groups in research is a prevailing problem due to multi-faceted barriers acting at multiple levels. Therefore, we rapidly reviewed international published literature, in relation to clinical trials, on barriers relating to inclusion, and evidence of approaches that are effective in overcoming these.
Methods
A rapid literature review was conducted searching PubMed for peer-reviewed articles that discussed barriers to inclusion or strategies to improve inclusion in clinical trial research published between 2010 and 2021. Grey literature articles were excluded.
Results
Seventy-two eligible articles were included. The main barriers identified were language and communication, lack of trust, access to trials, eligibility criteria, attitudes and beliefs, lack of knowledge around clinical trials, and logistical and practical issues. In relation to evidence-based strategies and enablers, two key themes arose: 1 a multi-faceted approach is essential 2; no single strategy was universally effective either within or between trials. The key evidence-based strategies identified were cultural competency training, community partnerships, personalised approach, multilingual materials and staff, communication-specific strategies, increasing understanding and trust, and tackling logistical barriers.
Conclusions
Many of the barriers relating to inclusion are the same as those that impact trial design and healthcare delivery generally. However, the presentation of these barriers among different under-served groups may be unique to each population’s particular circumstances, background, and needs. Based on the literature, we make 15 recommendations that, if implemented, may help improve inclusion within clinical trials and clinical research more generally. The three main recommendations include improving cultural competency and sensitivity of all clinical trial staff through training and ongoing personal development, the need to establish a diverse community advisory panel for ongoing input into the research process, and increasing recruitment of staff from under-served groups. Implementation of these recommendations may help improve representation of under-served groups in clinical trials which would improve the external validity of associated findings.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is associated with a range of persistent symptoms impacting everyday functioning, known as post-COVID-19 condition or long ...COVID. We undertook a retrospective matched cohort study using a UK-based primary care database, Clinical Practice Research Datalink Aurum, to determine symptoms that are associated with confirmed SARS-CoV-2 infection beyond 12 weeks in non-hospitalized adults and the risk factors associated with developing persistent symptoms. We selected 486,149 adults with confirmed SARS-CoV-2 infection and 1,944,580 propensity score-matched adults with no recorded evidence of SARS-CoV-2 infection. Outcomes included 115 individual symptoms, as well as long COVID, defined as a composite outcome of 33 symptoms by the World Health Organization clinical case definition. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for the outcomes. A total of 62 symptoms were significantly associated with SARS-CoV-2 infection after 12 weeks. The largest aHRs were for anosmia (aHR 6.49, 95% CI 5.02-8.39), hair loss (3.99, 3.63-4.39), sneezing (2.77, 1.40-5.50), ejaculation difficulty (2.63, 1.61-4.28) and reduced libido (2.36, 1.61-3.47). Among the cohort of patients infected with SARS-CoV-2, risk factors for long COVID included female sex, belonging to an ethnic minority, socioeconomic deprivation, smoking, obesity and a wide range of comorbidities. The risk of developing long COVID was also found to be increased along a gradient of decreasing age. SARS-CoV-2 infection is associated with a plethora of symptoms that are associated with a range of sociodemographic and clinical risk factors.
In the present study we characterize the properties of the potent MCT1 (monocarboxylate transporter 1) inhibitor AR-C155858. Inhibitor titrations of L-lactate transport by MCT1 in rat erythrocytes ...were used to determine the Ki value and number of AR-C155858-binding sites (Et) on MCT1 and the turnover number of the transporter (kcat). Derived values were 2.3+/-1.4 nM, 1.29+/-0.09 nmol per ml of packed cells and 12.2+/-1.1 s-1 respectively. When expressed in Xenopus laevis oocytes, MCT1 and MCT2 were potently inhibited by AR-C155858, whereas MCT4 was not. Inhibition of MCT1 was shown to be time-dependent, and the compound was also active when microinjected, suggesting that AR-C155858 probably enters the cell before binding to an intracellular site on MCT1. Measurement of the inhibitor sensitivity of several chimaeric transporters combining different domains of MCT1 and MCT4 revealed that the binding site for AR-C155858 is contained within the C-terminal half of MCT1, and involves TM (transmembrane) domains 7-10. This is consistent with previous data identifying Phe360 (in TM10) and Asp302 plus Arg306 (TM8) as key residues in substrate binding and translocation by MCT1. Measurement of the Km values of the chimaeras for L-lactate and pyruvate demonstrate that both the C- and N-terminal halves of the molecule influence transport kinetics consistent with our proposed molecular model of MCT1 and its translocation mechanism that requires Lys38 in TM1 in addition to Asp302 and Arg306 in TM8 Wilson, Meredith, Bunnun, Sessions and Halestrap (2009) J. Biol. Chem. 284, 20011-20021.
Understanding the long-term fate, stability, and bioavailability of uranium (U) in the environment is important for the management of nuclear legacy sites and radioactive wastes. Analysis of U ...behavior at natural analogue sites permits evaluation of U biogeochemistry under conditions more representative of long-term equilibrium. Here, we have used bulk geochemical and microbial community analysis of soils, coupled with X-ray absorption spectroscopy and μ-focus X-ray fluorescence mapping, to gain a mechanistic understanding of the fate of U transported into an organic-rich soil from a pitchblende vein at the UK Needle’s Eye Natural Analogue site. U is highly enriched in the Needle’s Eye soils (∼1600 mg kg−1). We show that this enrichment is largely controlled by U(VI) complexation with soil organic matter and not U(VI) bioreduction. Instead, organic-associated U(VI) seems to remain stable under microbially-mediated Fe(III)-reducing conditions. U(IV) (as non-crystalline U(IV)) was only observed at greater depths at the site (>25 cm); the soil here was comparatively mineral-rich, organic-poor, and sulfate-reducing/methanogenic. Furthermore, nanocrystalline UO2, an alternative product of U(VI) reduction in soils, was not observed at the site, and U did not appear to be associated with Fe-bearing minerals. Organic-rich soils appear to have the potential to impede U groundwater transport, irrespective of ambient redox conditions.
•Up to 1600 mg kg−1 U(VI)(s) retained in Needle’s Eye soils by organic complexation.•Uranyl-organic complexes stable under Fe(III)-reducing conditions.•U(VI) reduced to non-crystalline U(IV) under sulfate reducing/methanogenic conditions.•U hard to remobilise from Needle’s Eye soil.
Height is an important characteristic in the equine industry although little is known about its genetic control in native British breeds of ponies. This study aimed to map QTL data with the withers ...height in four pony breeds native to the British Isles, including two different sections within Welsh Cobs. In this study, a genome-wide analysis approach using the Illumina EquineSNP50 Infinium BeadChip was applied to 105 ponies and cobs. Analysis identified 222 highly significant height-associated SNPs (P ≤ 10
−5
), among which three SNPs on ECA9 have also been previously reported elsewhere. The highest number of significant SNPs associated to height in the native British horses were located on ECA1, ECA8, and ECA16.
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly ...1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15541. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
Recently, a cross‐talk error with commercial multiple breath nitrogen washout (MBWN2) software was discovered, which produced an absolute over‐reading of N2 of approximately 1%, i.e., 2% N2 read as ...3%. This caused an extended tail to the washout, and over‐estimated lung clearance index (LCI2.5) values. Subsequently an updated and corrected software version has been released. Within the field there have been discussions on how to correct legacy data, whether to migrate or completely “rerun” raw data A‐files from the old software into the new corrected software. To our knowledge, no research has been published assessing whether either method is equivalent to directly collecting data in the new corrected software. We prospectively recruited 19 participants, 10 adult healthy controls and 9 people with cystic fibrosis (CF). MBWN2 was performed using the Exhalyzer® D first on the old 3.1.6 software and next, directly on corrected 3.3.1 software. Multiple breath washout (MBW) data directly collected in 3.3.1 was significantly different from both migrated and rerun data. A total of 7 of the 19 participants (37%; 4 CF) had a relative difference in LCI2.5 > 10% for both migrated and rerun data compared to 3.3.1 collected data. Our findings have implications for the Global Lung Initiative MBW project, which is accepting a combination of directly collected, A‐file reruns and migrated data to establish normative values. Further, caution must be used in clinical practice when comparing corrected legacy data versus 3.3.1 collected data for clinical interpretation. We recommend that a new baseline is collected directly on 3.3.1. before clinical interpretation and decisions are determined when comparing consecutive MBW tests.
Aim To assess the reliability and accuracy of medical advice, over a range of types of websites, found using the Google search engine, thus simulating a patient's experience. Design Advice was sought ...for five common paediatric questions using the Google search engine. The first 100 results of each question were classified as either being consistent or inconsistent with current recommendations or as ‘no answer given’. Record of the type of site and its visibility was noted. Results 39% of the 500 sites searched gave correct information; 11% were incorrect and 49% failed to answer the question. Where an answer was available, 78% of sites gave the correct information. The accuracy of information varied depending on the topic and ranged from 51% (mumps, measles and rubella and autism) to 100% (breast feeding with mastitis/the sleeping position of a baby). Governmental sites gave uniformly accurate advice. News sites gave correct advice in 55% of cases. No sponsored sites were encountered that gave the correct advice. Implications The authors have shown that the advice on the internet is very variable. Patients are known to use the internet for their own research and as such the authors encourage healthcare workers to recommend government or NHS websites.
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