A report from the NIHR UK working group on remote trial delivery for the COVID-19 pandemic and beyond

Abstract Background Prior to the COVID-19 pandemic, the majority of clinical trial activity took place face to face within clinical or research units. The COVID-19 pandemic resulted in a significant shift towards trial delivery without in-person face-to-face contact or “Remote Trial Delivery”. The National Institute of Health Research (NIHR) assembled a Remote Trial Delivery Working Group to consider challenges and enablers to this major change in clinical trial delivery and to provide a toolkit for researchers to support the transition to remote delivery. Methods The NIHR Remote Trial Delivery Working Group evaluated five key domains of the trial delivery pathway: participant factors, recruitment, intervention delivery, outcome measurement and quality assurance. Independent surveys were disseminated to research professionals, and patients and carers, to ascertain benefits, challenges, pitfalls, enablers and examples of good practice in Remote Trial Delivery. A toolkit was constructed to support researchers, funders and governance structures in moving towards Remote Trial Delivery. The toolkit comprises a website encompassing the key principles of Remote Trial Delivery, and a repository of best practice examples and questions to guide research teams. Results The patient and carer survey received 47 respondents, 34 of whom were patients and 13 of whom were carers. The professional survey had 115 examples of remote trial delivery practice entered from across England. Key potential benefits included broader reach and inclusivity, the ability for standardisation and centralisation, and increased efficiency and patient/carer convenience. Challenges included the potential exclusion of participants lacking connectivity or digital skills, the lack of digitally skilled workforce and appropriate infrastructure, and validation requirements. Five key principles of Remote Trial Delivery were proposed: national research standards, inclusivity, validity, cost-effectiveness and evaluation of new methodologies. Conclusions The rapid changes towards Remote Trial Delivery catalysed by the COVID-19 pandemic could lead to sustained change in clinical trial delivery. The NIHR Remote Trial Delivery Working Group provide a toolkit for researchers recommending five key principles of Remote Trial Delivery and providing examples of enablers. </jats:sec

Global asthma prevalence in adults: findings from the cross-sectional world health survey

<p>Abstract</p> <p>Background</p> <p>Asthma is a major cause of disability, health resource utilization and poor quality of life world-wide. We set out to generate estimates of the global burden of asthma in adults, which may inform the development of strategies to address this common disease.</p> <p>Methods</p> <p>The World Health Survey (WHS) was developed and implemented by the World Health Organization in 2002-2003. A total of 178,215 individuals from 70 countries aged 18 to 45 years responded to questions related to asthma and related symptoms. The prevalence of asthma was based on responses to questions relating to self-reported doctor diagnosed asthma, clinical/treated asthma, and wheezing in the last 12 months.</p> <p>Results</p> <p>The global prevalence rates of doctor diagnosed asthma, clinical/treated asthma and wheezing in adults were 4.3%, 4.5%, and 8.6% respectively, and varied by as much as 21-fold amongst the 70 countries. Australia reported the highest rate of doctor diagnosed, clinical/treated asthma, and wheezing (21.0%, 21.5%, and 27.4%). Amongst those with clinical/treated asthma, almost 24% were current smokers, half reported wheezing, and 20% had never been treated for asthma.</p> <p>Conclusions</p> <p>This study provides a global estimate of the burden of asthma in adults, and suggests that asthma continues to be a major public health concern worldwide. The high prevalence of smoking remains a major barrier to combating the global burden of asthma. While the highest prevalence rates were observed in resource-rich countries, resource-poor nations were also significantly affected, posing a barrier to development as it stretches further the demands of non-communicable diseases.</p

Genetic analysis of lung function in inbred mice suggests vitamin D receptor as a candidate gene

Vitamin D receptor (VDR) polymorphisms are associated with an increased asthma incidence in human populations; however, observations in Vdr knockout mice are unclear. The aim of our study was to determine the influence of the genetic variation in Vdr among inbred strains on lung resistance (i.e., dynamic and airway resistance). In an intercross between the strains C57BL/6J (B6) and KK/HlJ (KK), we identified that a significant QTL for dynamic resistance on Chr X was interacting with a QTL on Chr 15. The Chr 15 QTL peak was located in close proximity to the Vdr locus. We further examined if phenotypes of several inbred strains with varying Vdr genotypes differed. Strains with a B6-like genotype on the Vdr locus had significantly lower airway resistance than strains with a KK-like genotype. Vdr knockout mice were examined for dynamic resistance and showed significantly higher resistance than mice with one (i.e., heterozygous) or both copies (i.e., wild-type) of the Vdr. In comparison to B6, the strain A/J is more resistant but carries the same genotype at the Vdr locus. Dietary vitamin D manipulation in the strain A/J did not rescue the high airway resistance phenotype. Finally, we observed that serum vitamin D does not correlate significantly with lung resistance parameters in a survey of 18 strains. Conclusively, Vdr contributes to the phenotypic variation of lung resistance in inbred mice but other molecules in the Vdr pathway and extended network [i.e., Chr X gene(s)] may contribute as well

The Q2Q^2-dependence of the generalised Gerasimov-Drell-Hearn integral for the deuteron, proton and neutron

The Gerasimov-Drell-Hearn (GDH) sum rule connects the anomalous contribution to the magnetic moment of the target nucleus with an energy-weighted integral of the difference of the helicity-dependent photoabsorption cross sections. The data collected by HERMES with a deuterium target are presented together with a re-analysis of previous measurements on the proton. This provides a measurement of the generalised GDH integral covering simultaneously the nucleon-resonance and the deep inelastic scattering regions. The contribution of the nucleon-resonance region is seen to decrease rapidly with increasing $Q^2$. The DIS contribution is sizeable over the full measured range, even down to the lowest measured $Q^2$. As expected, at higher $Q^2$ the data are found to be in agreement with previous measurements of the first moment of $g_1$. From data on the deuteron and proton, the GDH integral for the neutron has been derived and the proton--neutron difference evaluated. This difference is found to satisfy the fundamental Bjorken sum rule at $Q^2 = 5$ GeV$^2$.Comment: 12 pages, 10 figure

Evidence for Quark-Hadron Duality in the Proton Spin Asymmetry A1A_1

Spin-dependent lepton-nucleon scattering data have been used to investigate the validity of the concept of quark-hadron duality for the spin asymmetry $A_1$. Longitudinally polarised positrons were scattered off a longitudinally polarised hydrogen target for values of $Q^2$ between 1.2 and 12 GeV$^2$ and values of $W^2$ between 1 and 4 GeV$^2$. The average double-spin asymmetry in the nucleon resonance region is found to agree with that measured in deep-inelastic scattering at the same values of the Bjorken scaling variable $x$. This finding implies that the description of $A_1$ in terms of quark degrees of freedom is valid also in the nucleon resonance region for values of $Q^2$ above 1.6 GeV$^2$.Comment: 5 pages, 1 eps figure, table added, new references added, in print in Phys. Rev. Let

The Q^2-Dependence of Nuclear Transparency for Exclusive ρ0\rho^0 Production

Exclusive coherent and incoherent electroproduction of the $\rho^0$ meson from $^1$H and $^{14}$N targets has been studied at the HERMES experiment as a function of coherence length ($l_c$), corresponding to the lifetime of hadronic fluctuations of the virtual photon, and squared four-momentum of the virtual photon ($-Q^2$). The ratio of $^{14}$N to $^1$H cross sections per nucleon, known as nuclear transparency, was found to increase (decrease) with increasing coherence length for coherent (incoherent) $\rho^0$ electroproduction. For fixed coherence length, a rise of nuclear transparency with $Q^2$ is observed for both coherent and incoherent $\rho^0$ production, which is in agreement with theoretical calculations of color transparency.Comment: 5 pages, 4 figure

Beam-Induced Nuclear Depolarisation in a Gaseous Polarised Hydrogen Target

Spin-polarised atomic hydrogen is used as a gaseous polarised proton target in high energy and nuclear physics experiments operating with internal beams in storage rings. When such beams are intense and bunched, this type of target can be depolarised by a resonant interaction with the transient magnetic field generated by the beam bunches. This effect has been studied with the HERA positron beam in the HERMES experiment at DESY. Resonances have been observed and a simple analytic model has been used to explain their shape and position. Operating conditions for the experiment have been found where there is no significant target depolarisation due to this effect.Comment: REVTEX, 6 pages, 5 figure

Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron

The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2] for the proton and neutron have been determined from measurements of polarised cross section asymmetries in deep inelastic scattering of 27.5 GeV longitudinally polarised positrons from polarised 1H and 3He internal gas targets. The data were collected in the region above the nucleon resonances in the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the proton the contribution to the generalised Gerasimov-Drell-Hearn integral was found to be substantial and must be included for an accurate determination of the full integral. Furthermore the data are consistent with a QCD next-to-leading order fit based on previous deep inelastic scattering data. Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte

Measurement of the Proton Spin Structure Function g1p with a Pure Hydrogen Target

A measurement of the proton spin structure function g1p(x,Q^2) in deep-inelastic scattering is presented. The data were taken with the 27.6 GeV longitudinally polarised positron beam at HERA incident on a longitudinally polarised pure hydrogen gas target internal to the storage ring. The kinematic range is 0.021<x<0.85 and 0.8 GeV^2<Q^2<20 GeV^2. The integral Int_{0.021}^{0.85} g1p(x)dx evaluated at Q0^2 of 2.5 GeV^2 is 0.122+/-0.003(stat.)+/-0.010(syst.).Comment: 7 pages, 3 figures, 1 table, RevTeX late