bluuebunny/crossref_metadata_2025 huggingface dataset:
New ways of working releasing general practitioner capacity with pharmacy prescribing support: a cost-consequence analysis
Authors: Johnson Chris F , Maskrey Margaret , MacBride-Stewart Sean , Lees Ann , Macdonald Hector , Thompson Audrey
Published: December 2021

Background

General practice in the United Kingdom is experiencing a workforce crisis. Greater multidisciplinary working, including more general practice pharmacists, is seen as part of the solution. However, it is unknown what impact and cost-consequences that pharmacists may have in freeing general practitioner (GP) capacity.

Objective

To evaluate the cost-consequences of additional pharmacists in releasing GP capacity.

Methods

This cost-consequences evaluation of a prospective observational cohort study in 15 urban practices involving 69 GPs in 1 locality serving a population of 82,000 people. GPs recorded the time they spent addressing key targeted prescribing activities during 5 distinct 2-week audit periods. Pharmacists performed these key prescribing activities to release GP capacity. An additional 225 h of pharmacists’ time per week was committed to the locality. Standardized staff costings were used to estimate the financial impact. Prescribing indicator performance was assessed against the other 7 localities within the health board.

Results

When compared with employing extra nonsalaried GPs this required an estimated additional investment of £16.73 (range £5.97–20.87) per h to free GP capacity. This achieved a sustainable 47% (73 h per week, F(4,56) = 16.05, P < 0.001) reduction in GP time spent on key prescribing activities; equating to 4.9 h (95% confidence interval 3.1–6.7) per practice per week. No significant step changes in locality safety and quality prescribing measures, and no negative effects on locality-level prescribing cost-efficiency work were observed.

Conclusion

Appropriately resourced general practice pharmacy teams delivered prescribing cost-efficiencies as well as sustainably freeing GP capacity by performing key prescribing activities.
Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer’s Dementia
Authors: Cosarderelioglu Caglar , Nidadavolu Lolita S , George Claudene J , Marx-Rattner Ruth , Powell Laura , Xue Qian-Li , Tian Jing , Salib Joy , Oh Esther S , Ferrucci Luigi , Dincer Pervin , Bennett David A , Walston Jeremy D , Abadir Peter M
Published: December 2021

Aging is a key risk factor in Alzheimer’s dementia (AD) development and progression. The primary dementia-protective benefits of angiotensin II subtype 1 receptor (AT1R) blockers are believed to arise from systemic effects on blood pressure. However, a brain-specific renin-angiotensin system (b-RAS) exists, which can be altered by AT1R blockers. Brain RAS acts mainly through 3 angiotensin receptors: AT1R, AT2R, and AT4R. Changes in these brain angiotensin receptors may accelerate the progression of AD. Using postmortem frontal cortex brain samples of age- and sex-matched cognitively normal individuals (n = 30) and AD patients (n = 30), we sought to dissect the b-RAS changes associated with AD and assess how these changes correlate with brain markers of oxidative stress, inflammation, and mitochondrial dysfunction as well as amyloid-β and paired helical filament tau pathologies. Our results show higher protein levels of the pro-inflammatory AT1R and phospho-ERK (pERK) in the brains of AD participants. Brain AT1R levels and pERK correlated with higher oxidative stress, lower cognitive performance, and higher tangle and amyloid-β scores. This study identifies molecular changes in b-RAS and offers insight into the role of b-RAS in AD-related brain pathology.
Evaluation of long-lasting insecticidal net distribution through schools in Southern Tanzania
Authors: Stuck Logan , Chacky Frank , Festo Charles , Lutambi Angelina , Abdul Ramadhani , Greer George , Mandike Renata , Nathan Rose , Elisaria Ester , Yukich Joshua
Published: December 2021

Universal coverage with effective vector control remains the mainstay of malaria vector control in sub-Saharan Africa. Tanzania has utilized a number of mechanisms for the maintenance of long-lasting insecticidal net (LLIN) coverage over time. Schools have been identified as one potential channel for continuous distribution of LLIN. This research aims to evaluate an annual school-based LLIN distribution programme in Tanzania that began in 2013, called the School Net Programme (SNP). Following each of the first four rounds of SNP distribution, a household survey was conducted in intervention and comparison districts in Southern and Lake zones of Tanzania (N = 5083 households). Measures of ownership, access and use were compared between intervention and comparison districts. Determinants of reach were assessed in intervention districts. Population access to an LLIN increased from 63.1% (95% CI: 58.8, 67.5) to 76.5% (95% CI: 72.9, 80.0) in the intervention districts between the first and last surveys. Access also rose in the comparison districts from 51.4% (95% CI: 46.9, 55.9) to 79.8% (95% CI: 77.3, 82.0) following mass distribution and implementation of school-based distribution during the study period. LLIN use increased in intervention districts from 44.9% (95% CI: 40.5, 49.3) to 65.6% (95% CI: 59.4, 71.8) and from 57.2% (95% CI: 49.7, 64.7) to 77.4% (95% CI: 69.3, 85.5) specifically amongst primary school-aged children. Households reached by the SNP were wealthier households with children enrolled in school. The SNP in Tanzania was able to maintain population level LLIN ownership, use and access in the absence of mass distribution. The SNP successfully reached households that housed school-aged children. Alternative delivery strategies may need to be considered to reach households without children enrolled in schools that experienced fewer benefits from the programme.
Post-medistinoscopy chylopericardium
Authors: Abbas Sherif , Purohit Manoj , Cassidy Christopher
Published: December 2021

Isolated Chylopericardium (without chylothorax) is a rare clinical disorder that may happen idiopathically or secondary to trauma, radiotherapy, lymphatic anomalies, infections or mediastinal neoplasm. We present a case of middle-aged male with no past medical history of note prior to developing heavy sweating, loss of weight and cough. A series of investigations were done including chest computed tomography which showed enlarged mediastinal lymph nodes leading to uncomplicated mediastinoscopy and lymph node biopsy. Six days after being discharged, he developed dyspnoea and chest pain. Echocardiography revealed massive pericardial effusion. Pericardiocentesis was done and surprisingly revealed milky white chylous fluid. The patient was then successfully managed without the need for further intervention.
Improving results management processes in an acute hospital using a multi-faceted approach
Authors: Koh Darrel , Wee Tracy , Fong Michelle , Tan Xiaohui , Tan Rudyanna , Menon Shalini , Goh Joey , Teo Stephanie , Chia Joanna , Kristanto William , Lim Ghee Hian
Published: December 2021

Background

Radiological examinations and laboratory tests are routinely ordered by hospital physicians as part of the care plan to diagnose and treat patients. However, the failure to actively review and follow-up on these results pose a significant problem to patient safety. A study team was formed to mitigate the clinical risks of poor results management, which was identified as a top clinical risk in our organization, in order to make improvements to the results management process and to ensure the timely review, acknowledgement and follow-up of test results.

Objective

This study was carried out to improve results management processes and ensure the timely review, acknowledgment, and follow-up of test results, in order to mitigate the clinical risks posed to patient safety.

Methods

The institutional expectations of results management were set and published as a hospital policy, which was communicated to all clinical departments for compliance. Improvements to the electronic medical records system were made to facilitate the results acknowledgement process, and physicians were engaged to educate them on the importance of results management.

Results

The study team observed a decrease in unacknowledged results from approximately 16 000 in March 2017 to 2673 in December 2020. The compliance rate for acknowledgement results increased from a monthly average of 83.7% (from March to December 2017) to a monthly average of 99.3% (in 2020). The risk score for results management decreased from 16 to 6.5 and was excluded from the organization’s top clinical risks.

Conclusion

This study showed the importance of both system improvements and culture changes that are required to improve the process of results management and provides a step forward for the hospital to safeguard patient safety and mitigate clinical risk.
Haemin deprivation renders Bacteroides fragilis hypersusceptible to metronidazole and cancels high-level metronidazole resistance
Authors: Paunkov Ana , Gutenbrunner Katrin , Sóki József , Leitsch David
Published: December 2021

Background

Infections with Bacteroides fragilis are routinely treated with metronidazole, a 5-nitroimidazole antibiotic that is active against most anaerobic microorganisms. Metronidazole has remained a reliable treatment option, but resistance does occur, including in B. fragilis.

Objectives

In this study we tested whether haemin, a growth supplement for B. fragilis in vivo and in vitro, had an influence on the susceptibility of resistant B. fragilis strains to metronidazole. We further tested whether haemin-deprived B. fragilis would be more susceptible to oxygen and oxidative stress. Metronidazole has been described to cause oxidative stress, which we argued would be exacerbated in haemin-deprived B. fragilis because the bacteria harness haemin, and the iron released from it, in antioxidant enzymes such as catalase and superoxide dismutase.

Methods

Haemin was omitted from growth media and the effect on metronidazole susceptibility was monitored in susceptible and resistant B. fragilis strains. Further, haemin-deprived B. fragilis were tested for resistance to aeration and hydrogen peroxide and the capacity for the removal of oxygen.

Results

Omission of haemin from the growth medium rendered metronidazole-resistant B. fragilis strains, including an MDR isolate from the UK, highly susceptible to metronidazole. Haemin deprivation further rendered B. fragilis highly susceptible to oxygen, which was further exacerbated in resistant strains. B. fragilis was incapable of scavenging oxygen when haemin was omitted.

Conclusions

We propose that haemin deprivation overrules resistance mechanisms by rendering B. fragilis hypersusceptible to metronidazole due to a compromised antioxidant defence. Monitoring of haemin concentrations is imperative when conducting metronidazole susceptibility testing in B. fragilis.
More Brutal than Alton West? Elevation Design and the Gordon Wilson Memorial Flats, Wellington, New Zealand
Authors: McCarthy Christine , Dudding Michael
Published: December 2021

This paper addresses a gap in research regarding the design of the main elevations of the Gordon Wilson Memorial Flats (GWF). The GWF is the only surviving post-war example of high-rise multi-unit state housing in New Zealand. Its identification as a heritage building has been controversial, but this status was recently confirmed in New Zealand’s Environment Court. This paper examines the GWF elevations in the context of the building’s precedent, the London County Council-designed Alton West housing blocks. It concludes that the GWF façade designs are compellingly New Brutalist because they directly express conditions of living, including the structure, construction, and maisonette planning of the building, while negotiating the aesthetic dilemmas of mid-twentieth century flat block design, positioning the building as an important development in modernist residential high-rise blocks.
Tracking causal relations in the news: data, tools, and models for the analysis of argumentative statements in online media
Authors: Willaert Tom , Banisch Sven , Van Eecke Paul , Beuls Katrien
Published: December 2021

Online debates and debate spheres challenge our assumptions about democracy, politics, journalism, trust, and truth in ways that make them a necessary object of study. In the present article, we argue that the study of online arguments can benefit from an interdisciplinary approach that combines computational methods for text analysis with conceptual models of opinion dynamics. The article thereby seeks to make a conceptual and methodological contribution to the field by highlighting the role of domain-crossing causal statements in debates of societal interest, and by providing a method for automatically mining such statements from textual corpora on the web. The article illustrates the relevance of this approach for the study of online debates by means of a case study in which we analyse cross-cutting statements on climate change and energy technologies from the comment section of the online newspaper The Guardian. In support of this case study, we use data and methods that are made openly available through the Penelope ecosystem of tools and techniques for computational social science.
Selection and identification of an RNA aptamer that specifically binds the HIV-1 capsid lattice and inhibits viral replication
Authors: Gruenke Paige R , Aneja Rachna , Welbourn Sarah , Ukah Obiaara B , Sarafianos Stefan G , Burke Donald H , Lange Margaret J
Published: December 2021

The HIV-1 capsid core participates in several replication processes. The mature capsid core is a lattice composed of capsid (CA) monomers thought to assemble first into CA dimers, then into ∼250 CA hexamers and 12 CA pentamers. CA assembly requires conformational flexibility of each unit, resulting in the presence of unique, solvent-accessible surfaces. Significant advances have improved our understanding of the roles of the capsid core in replication; however, the contributions of individual CA assembly forms remain unclear and there are limited tools available to evaluate these forms in vivo. Here, we have selected aptamers that bind CA lattice tubes. We describe aptamer CA15-2, which selectively binds CA lattice, but not CA monomer or CA hexamer, suggesting that it targets an interface present and accessible only on CA lattice. CA15-2 does not compete with PF74 for binding, indicating that it likely binds a non-overlapping site. Furthermore, CA15-2 inhibits HIV-1 replication when expressed in virus producer cells, but not target cells, suggesting that it binds a biologically-relevant site during virus production that is either not accessible during post-entry replication steps or is accessible but unaltered by aptamer binding. Importantly, CA15-2 represents the first aptamer that specifically recognizes the HIV-1 CA lattice.
What Do Police Interview Eyewitnesses for? A Review
Authors: Launay Céline , Brunel Maïté , Bull Ray
Published: December 2021

The objective of witness investigative interviews is to collect reliable and relevant information. This review aims to document what constitutes relevant information, as well as the techniques that researchers have built or still need to build to reliably collect this information. Researchers and practitioners agree on the ‘investigation-relevant information’ to be collected, which represents around 80% of the content of the investigative interviews (i.e. actions, persons, objects, contextual details, sounds/conversations, and gist information). Many techniques have been developed by researchers to reliably collect most of them. Another content of the interview has largely been neglected in research studies: information pertaining to the interviewee, which represents around 20% of the content of the interviews. We identified six sub-categories: witness characteristics, meta-cognition, viewing conditions, witness’ role, witness’ state, and general knowledge. Several existing techniques could be useful to reliably collect this information but more research is needed. Implications for improving interviewing guidance will be discussed.
Virtual reality for public health: a study on a VR intervention to enhance occupational injury prevention
Authors: Namkoong Kang , Chen Junhan , Leach John , Song Yongwook , Vincent Stacy , Byrd Alex P , Mazur Joan
Published: December 2021

Background

Agriculture is one of the most hazardous occupations in the USA. Especially, tractor rollover incidents are the leading cause of farming-related injuries or deaths. This study examines the effect of a VR intervention (Virtual Reality Intervention for Safety Education; VRISE) on behavioral intentions for occupational safety and identifies a psychological mechanism that shows how the immersive technology works.

Methods

VRISE was developed by a multidisciplinary team of agricultural educators, computer scientists and communication specialists. It was designed to provide a virtual environment where users practice tractor operation and try to avoid several rollover hazards. The participants (291 high school students) were recruited at the 2019 National Future Farmers Association Convention & Expo and randomly assigned to one of three conditions: two different types of control groups (Control1: No treatment group and Control2: 2D Screen group) and the treatment group.

Results

Findings show that, through the immersive VR experience, the VR intervention enhanced perceived threat of tractor-related accidents which in turn, led to improved behavioral intentions for tractor safety.

Conclusions

Findings shed light on the effectiveness of a VR intervention to improve public health outcomes, especially in occupational safety education, where unsafe practices often result in injury and fatality.
Marginal Effects of Merit Aid for Low-Income Students
Authors: Angrist Joshua , Autor David , Pallais Amanda
Published: December 2021

Financial aid from the Susan Thompson Buffett Foundation (STBF) provides comprehensive support to a student population similar to that served by a host of state aid programs. In conjunction with STBF, we randomly assigned aid awards to thousands of Nebraska high school graduates from low-income, minority, and first-generation college households. Randomly assigned STBF awards boost bachelor’s (BA) degree completion for students targeting four-year schools by about 8 points. Degree gains are concentrated among four-year college applicants who would otherwise have been unlikely to pursue a four-year program. Degree effects are mediated by award-induced increases in credits earned toward a BA in the first year of college. The extent of initial four-year college engagement explains differences in impact by target campus and across covariate subgroups. The projected lifetime earnings effect of awards exceeds marginal educational spending for all of the subgroups examined in the study. Projected earnings gains exceed funder costs for urban students and for students with relatively weak academic preparation.
Will ‘the feeling of abandonment’ remain? Persisting impacts of the COVID-19 pandemic on rheumatology patients and clinicians
Authors: Sloan Melanie , Harwood Rupert , Gordon Caroline , Bosley Michael , Lever Elliott , Modi Rakesh , Blane Moira , Brimicombe James , Barrere Colette , Holloway Lynn , Sutton Stephen , D’Cruz David
Published: December 2021

Objective

To better understand rheumatology patient and clinician pandemic-related experiences, medical relationships and behaviours in order to help identify the persisting impacts of the COVID-19 pandemic and inform efforts to ameliorate the negative impacts and build upon the positive ones.

Methods

Rheumatology patients and clinicians completed surveys (patients n = 1543, clinicians n = 111) and interviews (patients n = 41, clinicians n = 32) between April 2021 and August 2021. A cohort (n = 139) of systemic autoimmune rheumatic disease patients was also followed up from March 2020 to April 2021. Analyses used sequential mixed methods. Pre-specified outcome measures included the Warwick–Edinburgh Mental wellbeing score (WEMWBS), satisfaction with care and healthcare behaviours.

Results

We identified multiple ongoing pandemic-induced/increased barriers to receiving care. The percentage of patients agreeing they were medically supported reduced from 74.4% pre-pandemic to 39.7% during-pandemic. Ratings for medical support, medical security and trust were significantly (P <0.001) positively correlated with patient WEMWBS and healthcare behaviours, and decreased during the pandemic. Healthcare-seeking was reduced, potentially long-term, including from patients feeling ‘abandoned’ by clinicians, and a ‘burden’ from government messaging to protect the NHS. Blame and distrust were frequent, particularly between primary and secondary care, and towards the UK government, who <10% of clinicians felt had supported clinicians during the pandemic. Clinicians’ efforts were reported to be impeded by inefficient administration systems and chronic understaffing, suggestive of the pandemic having exposed and exacerbated existing healthcare system weaknesses.

Conclusion

Without concerted action—such as rebuilding trust, improved administrative systems and more support for clinicians—barriers to care and negative impacts of the pandemic on trust, medical relationships, medical security and patient help-seeking may persist in the longer term.

Trial registration

This study is part of a pre-registered longitudinal multi-stage trial, the LISTEN study (ISRCTN-14966097), with later COVID-related additions registered in March 2021, including a pre-registered statistical analysis plan.
Deficiency of the minor spliceosome component U4atac snRNA secondarily results in ciliary defects
Authors: Khatri Deepak , Putoux Audrey , Cologne Audric , Kaltenbach Sophie , Besson Alicia , Bertiaux Eloïse , Guguin Justine , Fendler Adèle , Dupont Marie A. , Benoit-Pilven Clara , Grotto Sarah , Ruaud Lyse , Michot Caroline , Castelle Martin , Guët Agnès , Guibaud Laurent , Hamel Virginie , Bordonné Rémy , Leutenegger Anne-Louise , Attié-Bitach Tania , Edery Patrick , Mazoyer Sylvie , Delous Marion
Published: December 2021

In the human genome, about 750 genes contain one intron excised by the minor spliceosome. This spliceosome comprises its own set of snRNAs, among which U4atac. Its non-coding gene,RNU4ATAC, has been found mutated in Taybi-Linder (MOPD1/TALS), Roifman (RFMN) and Lowry-Wood syndromes (LWS). These rare developmental disorders, whose physiopathological mechanisms remain unsolved, associate ante- and post-natal growth retardation, microcephaly, skeletal dysplasia, intellectual disability, retinal dystrophy and immunodeficiency. Here, we report a homozygousRNU4ATACmutation in the Stem II domain, n.16G>A, in two unrelated patients presenting with both typical traits of the Joubert syndrome (JBTS), a well-characterized ciliopathy, and of TALS/RFMN/LWS, thus widening the clinical spectrum ofRNU4ATAC-associated disorders and indicating ciliary dysfunction as a mechanism downstream of minor splicing defects. This finding is supported by alterations of primary cilium function in TALS and JBTS/RFMN fibroblasts, as well as byu4ataczebrafish model, which exhibit ciliopathy-related phenotypes and ciliary defects. Altogether, our data indicate that alteration of cilium biogenesis is part of the physiopathological mechanisms of TALS/RFMN/LWS, secondarily to defects of minor intron splicing.
Comparative efficacy of tocilizumab and baricitinib in COVID-19 treatment: a retrospective cohort study
Authors: Kojima Yuichi , Nakakubo Sho , Kamada Keisuke , Yamashita Yu , Takei Nozomu , Nakamura Junichi , Matsumoto Munehiro , Horii Hiroshi , Sato Kazuki , Shima Hideki , Suzuki Masaru , Konno Satoshi
Published: December 2021

Background

Although biological agents, tocilizumab and baricitinib, have been shown to improve the outcomes of patients with COVID-19, a comparative evaluation has not been performed.

Methods

A retrospective, single-center study was conducted using the data of patients with COVID-19 admitted to the Hokkaido University hospital between April 2020 and September 2021, who were treated with tocilizumab or baricitinib. The clinical characteristics of patients who received each drug were compared. Univariate and multivariate logistic regression models were performed against the outcomes of all-cause mortality and the improvement in respiratory status. The development of secondary infection events was analyzed using the Kaplan–Meier analysis and the log-rank test.

Results

The use of tocilizumab or baricitinib was not associated with all-cause mortality and the improvement in respiratory status within 28 days of drug administration. Age, chronic renal disease, and comorbid respiratory disease were independent prognostic factors for all-cause mortality, while anti-viral drug use and severity of COVID-19 at baseline were associated with the improvement in respiratory status. There was no significant difference in the infection-free survival between patients treated with tocilizumab and those with baricitinib.

Conclusion

There were no differences in efficacy and safety between tocilizumab and baricitinib for the treatment of COVID-19.
Non-rapid eye movement sleep and wake neurophysiology in schizophrenia
Authors: Kozhemiako Nataliia , Wang Jun , Jiang Chenguang , Wang Lei , Gai Guan-chen , Zou Kai , Wang Zhe , Yu Xiao-man , Zhou Lin , Li Shen , Guo Zhenglin , Law Robert G. , Coleman James , Mylonas Dimitrios , Shen Lu , Wang Guoqiang , Tan Shuping , Qin Shengying , Huang Hailiang , Murphy Michael , Stickgold Robert , Manoach Dara S. , Zhou Zhenhe , Zhu Wei , Hall Mei-Hua , Purcell Shaun M. , Pan Jen Q.
Published: December 2021

Motivated by the potential of objective neurophysiological markers to index thalamocortical function in patients with severe psychiatric illnesses, we comprehensively characterized key NREM sleep parameters across multiple domains, their interdependencies, and their relationship to waking event-related potentials and symptom severity. In 130 schizophrenia (SCZ) patients and controls, we confirmed a marked reduction in sleep spindle density in SCZ and extended these findings to show that only slow spindles predicted symptom severity, and that fast and slow spindle properties were largely uncorrelated. We also describe a novel measure of slow oscillation and spindle interaction that was attenuated in SCZ. The main sleep findings were replicated in a demographically distinct sample, and a joint model, based on multiple NREM components, predicted disease status in the replication cohort. Although also altered in patients, auditory event-related potentials elicited during wake were unrelated to NREM metrics. Consistent with a growing literature implicating thalamocortical dysfunction in SCZ, our characterization identifies independent NREM and wake EEG biomarkers that may index distinct aspects of SCZ pathophysiology and point to multiple neural mechanisms underlying disease heterogeneity. This study lays the groundwork for evaluating these neurophysiological markers, individually or in combination, to guide efforts at treatment and prevention as well as identifying individuals most likely to benefit from specific interventions.
Effect of Light Conditions onIn VitroAdventitious Organogenesis of Cucumber Cultivars
Authors: Miguel Jorge Fonseca
Published: December 2021

The response on callus and shoot formation under different light incubation conditions was evaluated in cucumber (Cucumis sativusL.). Four-day-old cotyledon explants from the inbred line ‘Wisconsin 2843’ and the commercial cultivars ‘Marketer’ and ‘Negrito’ were employed. A four-week culture was conducted on MS-derived shoot induction medium containing 0.5 mg L-1 IAA and 2.5 mg L-1 BAP, under an 8-h dark/ 16-h light regime, or by a one- or two-week dark pre-incubation followed by the same photoperiod. Significant differences were obtained for the regeneration of shoots in all cultivars. The response in both frequency and number of shoots under continuous photoperiod was at least 3-6 fold higher than with dark pre-incubation. The highest genotypes response was obtained by ‘Negrito’ and ‘Marketer’ with identical values. All explants formed callus, and in two of the three cultivars, the response on callus extension was not significantly affected by incubation conditions. The results clearly show that shoot induction under continuous photoperiod regime was beneficial for adventitious shoot regeneration in cucumber.
COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database
Authors: Keh Ryan Y.S. , Scanlon Sophie , Datta-Nemdharry Preeti , Donegan Katherine , Cavanagh Sally , Foster Mark , Skelland David , Palmer James , Machado Pedro M. , Keddie Stephen , Carr Aisling S. , Lunn Michael P. ,   BPNS/ABN COVID-19 Vaccine GBS Study Group
Published: December 2021

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS). An association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service data in England and a multicentre surveillance study from UK hospitals, to investigate the relationship between COVID-19 vaccination and GBS.

Firstly, case dates of GBS identified retrospectively in the National Immunoglobulin Database from 8 December 2021 to 8 July 2021 were linked to receipt dates of a COVID-19 vaccines using data from the National Immunisation Management System in England. For the linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK-wide (four nations) GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database. For this multicentre UK-wide surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS.

996 GBS cases were recorded in the National Immunoglobulin Database from January to October 2021. A spike of GBS cases above the 2016-2020 average occurred in March-April 2021. 198 GBS cases occurred within 6 weeks of the first-dose COVID-19 vaccination in England (0.618 cases per 100,000 vaccinations, 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer), 1 mRNA-1273 (Moderna)). The 6-week excess of GBS (compared to the baseline rate of GBS cases 6-12 weeks after vaccination) occurs with a peak at 24 days post-vaccination; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases from January-July 2021 was between 98-140 cases for first-dose ChAdOx1 nCoV-19 vaccination. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. Detailed clinical data from 121 GBS patients were reported in the separate multicentre surveillance dataset during this timeframe. No phenotypic or demographic differences identified between vaccine-associated and non-vaccinated GBS cases occurring in the same timeframe.

Analysis of the linked NID/NIMS dataset suggests that first-dose ChAdOx1 nCoV-19 vaccination is associated with an excess GBS risk of 0.576 (95%CI 0.481-0.691) cases per 100,000 doses. However, examination of a multicentre surveillance dataset suggests that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19 specific first dose link warrants further study.
Differential Risk of SARS-CoV-2 Infection by Occupation: Evidence from the Virus Watch prospective cohort study in England and Wales
Authors: Beale Sarah , Hoskins Susan , Byrne Thomas , Erica Fong Wing Lam , Fragaszy Ellen , Geismar Cyril , Kovar Jana , Navaratnam Annalan M D , Nguyen Vincent , Patel Parth , Yavlinsky Alexei , Johnson Anne M , Van Tongeren Martie , Aldridge Robert W , Hayward Andrew
Published: December 2021

Background

Workers differ in their risk of SARS-CoV-2 infection according to their occupation, but the direct contribution of occupation to this relationship is unclear. This study aimed to investigate how infection risk differed across occupational groups in England and Wales up to April 2022, after adjustment for potential confounding and stratification by pandemic phase.

Methods

Data from 15,190 employed/self-employed participants in the Virus Watch prospective cohort study were used to generate risk ratios for virologically- or serologically-confirmed SARS-CoV-2 infection using robust Poisson regression, adjusting for socio-demographic and health-related factors and non-work public activities. We calculated attributable fractions (AF) amongst the exposed for belonging to each occupational group based on adjusted risk ratios (aRR).

Findings

Increased risk was seen in nurses (aRR=1.44, 1.25-1.65; AF=30%, 20-39%), doctors (aRR=1.33, 1.08-1.65; AF=25%, 7-39%), carers (1.45, 1.19-1.76; AF=31%, 16-43%), primary school teachers (aRR=1.67, 1.42-1.96; AF=40%, 30-49%), secondary school teachers (aRR=1.48, 1.26-1.72; AF=32%, 21-42%), and teaching support occupations (aRR=1.42, 1.23-1.64; AF=29%, 18-39%) compared to office-based professional occupations. Differential risk was apparent in the earlier phases (Feb 2020 - May 2021) and attenuated later (June - October 2021) for most groups, although teachers and teaching support workers demonstrated persistently elevated risk across waves.

Interpretation

Occupational differentials in SARS-CoV-2 infection risk vary over time and are robust to adjustment for socio-demographic, health-related, and non-workplace activity-related potential confounders. Direct investigation into workplace factors underlying elevated risk and how these change over time is needed to inform occupational health interventions.
Real-world data on immune responses following heterologous prime-boost COVID-19 vaccination schedule with Pfizer and AstraZeneca vaccines in England
Authors: Westrop Samantha J , Whitaker Heather J , Powell Annabel A , Power Linda , Whillock Corinne , Campbell Helen , Simmons Ruth , Warrener Lenesha , Ramsay Mary E , Ladhani Shamez N , Brown Kevin E , Amirthalingham Gayatri
Published: December 2021

Background
There are limited data on immune responses to heterologous COVID–19 immunisation schedules, especially following an extended ≥12–week interval between doses.
Methods
SARS–CoV–2 infection–naïve and previously–infected adults receiving ChAd–BNT (ChAdOx1 nCoV–19, AstraZeneca followed by BNT162b2, Pfizer–BioNTech) or BNT–ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti–SARS–CoV–2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd–ChAd or BNT–BNT.
Results
During March–October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously–uninfected adults, S–antibody GMC at 30 days post–second dose were lowest for ChAd–ChAd (862 (95%CI, 694– 1069)) and significantly higher for ChAd–BNT (6233 (5522– 7035); GMR 6.29; (5.04– 7.85); p<0.001), BNT-ChAd (4776 (4066– 5610); GMR 4.55 (3.56– 5.81); p<0.001) and BNT–BNT (5377 (4596– 6289); GMR 5.66 (4.49– 7.15); p<0.001). By 12 weeks after dose two, S–antibody GMC had declined in all groups and remained significantly lower for ChAd–ChAd compared to ChAd–BNT (GMR 5.12 (3.79– 6.92); p<0.001), BNT–ChAd (GMR 4.1 (2.96– 5.69); p<0.001) and BNT–BNT (GMR 6.06 (4.32– 8.50); p<0.001). Previously infected adults had higher S–antibody GMC compared to infection–naïve adults at all time–points and with all vaccine schedules.
Conclusions
These real–world findings demonstrate heterologous schedules with adenoviral–vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained.
Urinary sodium excretion is not associated with the incidence of end-stage kidney disease and kidney-related death: results from the UK Biobank
Authors: Shan Ying , Bai Yong , Zhang Jingwen , Lu Yueqi , Yu Sike , Song Congying , Liu Juehan , Jian Min , Xu Junjie , Xiong Zuying , Huang Xiaoyan
Published: December 2021

Background

Sodium reduction lowers blood pressure and albuminuria, indicating a hypothesized but yet-to-be proven association between sodium intake and kidney-related endpoints.

Objectives

We aimed to investigate the associations of 24-h urinary sodium excretion, reflecting daily sodium intake, with kidney-related outcomes.

Methods

Prospective cohort of 444,086 middle- to early late-aged participants from the UK Biobank. The primary outcome was a composite of incident end-stage kidney disease (ESKD) and death due to a kidney-related cause, each of which was separately examined as a secondary outcome. Death due to a non-kidney related cause prior to ESKD was considered a competing event.

Results

The mean 24-h urinary sodium excretion estimated from spot urinary biomarkers was 3.3 g. During a median follow-up of 11.8 years, 1,256 composite events occurred. Multivariable-adjusted cause-specific hazards models showed that, with every 1-g increment in 24-h urinary sodium excretion, hazard ratios (95% confidence intervals) were 1.03 (0.91-1.16), 1.08 (0.88-1.32), and 1.01 (0.88-1.16) for the composite outcome, incident ESKD, and kidney-related death, respectively. Similar null results were observed when the exposure was treated as binary (<2 g/d vs. ≥2 g/d) or multicategorical (quartiles). Nonlinear associations were not detected with restricted cubic splines. The findings also held constant in prespecified sensitivity and subgroup analyses.

Conclusions

Estimated 24-h urinary sodium excretion was not linearly or nonlinearly associated with the incidence of ESKD or death due to kidney-related causes. Our findings did not support the hypothesized notion that sodium intake should be reduced to prevent kidney-related endpoints at the population level.
Transmission of SARS-CoV-2 by children and young people in households and schools: a meta-analysis of population-based and contact-tracing studies
Authors: Viner Russell , Waddington Claire , Mytton Oliver , Booy Robert , Cruz Joana , Ward Joseph , Ladhani Shamez , Panovska-Griffiths Jasmina , Bonell Chris , Melendez-Torres G.J.
Published: December 2021

Background

The role of children and young people (CYP) in transmission of SARS-CoV-2 in household and educational settings remains unclear. We undertook a systematic review and meta-analysis of contact-tracing and population-based studies at low risk of bias.

Methods

We searched 4 electronic databases on 28 July 2021 for contact-tracing studies and population-based studies informative about transmission of SARS-CoV-2 from 0-19 year olds in household or educational settings. We excluded studies at high risk of bias, including from under-ascertainment of asymptomatic infections. We undertook multilevel random effects meta-analyses of secondary attack rates (SAR: contact-tracing studies) and school infection prevalence, and used meta-regression to examine the impact of community SARS-CoV-2 incidence on school infection prevalence.

Findings

4529 abstracts were reviewed, resulting in 37 included studies (16 contact-tracing; 19 population studies; 2 mixed studies). The pooled relative transmissibility of CYP compared with adults was 0.92 (0.68, 1.26) in adjusted household studies. The pooled SAR from CYP was lower (p=0.002) in school studies 0.7% (0.2, 2.7) than household studies (7.6% (3.6, 15.9). There was no difference in SAR from CYP to child or adult contacts. School population studies showed some evidence of clustering in classes within schools. School infection prevalence was associated with contemporary community 14-day incidence (OR 1.003 (1.001, 1.004), p<0.001).

Interpretation

We found no difference in transmission of SARS-CoV-2 from CYP compared with adults within household settings. SAR were markedly lower in school compared with household settings, suggesting that household transmission is more important than school transmission in this pandemic. School infection prevalence was associated with community infection incidence, supporting hypotheses that school infections broadly reflect community infections. These findings are important for guiding policy decisions on shielding, vaccination school and operations during the pandemic.

Funding

No funding obtained.
HIV Phylogenetics Reveals Overlapping Transmission Networks among Cities and Key Populations in Pakistan
Authors: de Bernardi Schneider Adriano , Cholette François , Pelcat Yann , Lim Aaron G. , Vickerman Peter T. , Hassan Adiba , Thompson Laura H. , Blanchard James F. , Emmanuel Faran , Reza Tahira , Dar Nosheen , Ikram Nadeem , Pilon Richard , Archibald Chris , Joy Jeffrey B. , Sandstrom Paul , Wertheim Joel O.
Published: December 2021

The first case of HIV in Pakistan was documented in 1987, with multiple subtypes and circulating recombinant forms being introduced and currently circulating in the country. Since then, there has been a shift in the country from a low prevalence/high risk to a high-risk concentrated epidemic. Pakistan’s epidemic is concentrated among key populations at greater risk of HIV infection including people who inject drugs (PWID), Hijra sex workers (HSW), female sex workers (FSW), male sex workers (MSW), and men who have sex with men (MSM). This study focused on the geographical aspect as well as on the interactions between key populations at higher risk of contracting HIV. We aimed at understanding the behavior of these key populations at a molecular level with high granularity as well as investigating the possibility of multiple HIV-1 introductions in Pakistan. In this cross-sectional biological and behavioral survey, we collected dried blood spots (DBS) for the purposes of seroprevalence estimates and molecular epidemiology from individuals in 17 cities in Pakistan representing four key populations: PWID, HSW, MSW, and FSW. A total of 1153 envelope sequences (reference positions in HXB2: 7860-8274) of HIV were sequenced using a Sanger-based sequencing approach. To identify clusters based on the introduction of the virus in Pakistan from foreign countries we added 3623 publicly available HIV envelope sequences to our dataset. Phylogeographic inference suggests at least 15 independent introductions of the virus into Pakistan, with a total of 12 clusters ranging from 3 to 675 sequences in size containing sequences from Pakistan and neighboring countries exclusively. Our phylogenetic analysis shows a significant degree of connectivity and directionality suggesting broad and overlapping networks of HIV-1 transmission among cities and key populations in Pakistan.
A Cloth Facemask Causes No Major Respiratory or Cardiovascular Perturbations during Moderate to Heavy Exercise
Authors: Guardieiro Natália Mendes , Barreto Gabriel , Marticorena Felipe Miguel , Oliveira Tamires Nunes , de Oliveira Luana Farias , de Sá Pinto Ana Lucia , do Prado Danilo Marcelo Leite , Saunders Bryan , Gualano Bruno
Published: December 2021

Objectives

To investigate whether wearing a cloth facemask could affect physiological and perceptual responses to exercise at distinct exercise intensities in non-trained men and women.

Methods

In a crossover design, participants (17 men and 18 women) underwent a progressive square-wave test at four intensities (i. at 80% of the ventilatory anerobic threshold [80%VAT]; ii. at VAT; iii. at the respiratory compensation point [RCP]; iv. at exercise peak [Peak] to exhaustion), with or without a triple-layered cloth mask (Mask or No-Mask). Several physiological, metabolic and perceptual measures were analyzed.

Results

Mask reduced inspiratory capacity at all exercise intensities vs. No-Mask (p<0.0001), irrespective of sex. Mask reduced respiratory frequency vs. No-Mask (p=0.001) at Peak (−8.3 breaths·min-1; CI: -5.8, -10.8), RCP (−6.9 breaths·min-1; CI: -4.6, -9.2) and VAT (−6.5 breaths·min-1; CI: -4.1, -8.8), but not at Baseline or at 80%VAT. Mask also reduced tidal volume (p<0.0001) at both RCP (−0.5L; CI: -0.3, -0.6) and Peak (−0.8L; CI: -0.6, -0.9), but not at Baseline, 80%VAT or VAT. Shallow breathing index was increased with Mask at Peak compared to No-Mask (11.3; CI: 7.5, 15.1), but not at any other intensities. Mask did not change heart rate, lactate, ratings of perceived exertion, blood pressure or oxygen saturation.

Conclusions

Wearing a cloth facemask during exercise at moderate to heavy intensities is unlikely to incur significant respiratory or cardiovascular changes, irrespective of sex. These data can inform new exercise recommendations for health during the COVID-19 pandemic and debunk unfounded allegations of harmful effects of masks during exercise. ClinicalTrials.gov: NCT04887714

What are the new findings?

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Using a progressive square-wave test, we showed that wearing a cloth facemask during exercise increased breathing difficulty, but this was dependent upon the exercise intensity.

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Respiratory variables (e.g., inspiratory capacity, respiratory frequency, shallow breathing index) were affected at higher rather than lower intensities.

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Mask wearing did not change heart rate, lactate, ratings of perceived exertion, blood pressure or oxygen saturation at any exercise intensity.

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There were no substantial sex differences on the effects of mask wearing during exercise.

How might it impact on clinical practice in the future?

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These data can debunk unfounded allegations on harmful effects of masks during exercise, and help inform new exercise recommendations for health during the COVID-19 pandemic, particularly where facemasks remain necessary.
Analytical Solution of a New SEIR Model Based on Latent Period-Infectious Period Chronological Order
Authors: Liu Xiaoping
Published: December 2021

The Susceptible-Infectious-Recovered (SIR) and SIR derived epidemic models have been commonly used to analyze the spread of infectious diseases. The underlying assumption in these models, such as Susceptible-Exposed-Infectious-Recovered (SEIR) model, is that the change in variables E, I or R at time t is dependent on a fraction of E and I at time t. This means that after exposed on a day, this individual may become contagious or even recover on the same day. However, the real situation is different: an exposed individual will become infectious after a latent period (l) and then recover after an infectious period (i). In this study, we proposed a new SEIR model based on the latent period-infectious period chronological order (Liu X., Results Phys. 2021; 20:103712). An analytical solution to equations of this new SEIR model was derived. From this new SEIR model, we obtained a propagated curve of infectious cases under conditions l>i. Similar propagated epidemic curves were reported in literature. However, the conventional SEIR model failed to simulate the propagated epidemic curves under the same conditions. For l<i, the new SEIR models generated bell-shaped curves for infectious cases, and the curve is near symmetrical to the vertical line passing the curve peak. This characteristic can be found in many epidemic curves of daily COVID-19 cases reported from different countries. However, the curve generated from the conventional SEIR model is a right-skewed bell-shaped curve. An example for applying the analytical solution of the new SEIR model equations to simulate the reported daily COVID-19 cases was also given in this paper.