bluuebunny/crossref_metadata_2025 huggingface dataset:
GMP‐grade CD34+ selection from HLA‐homozygous licensed cord blood units and short‐term expansion under European ATMP regulations
Authors: Liedtke Stefanie , Korschgen Lutz , Korn Janine , Duppers Almuth , Kogler Gesine
Published: July 2020

Background

Based on a synergistic consortium, the cord blood (CB) bank Düsseldorf was responsible for the selection of HLA‐homozygous (HLA‐h) donors, contacting/re‐consenting the mothers, Good Manufacturing Practice (GMP)‐grade CD34+ enrichment, followed by short‐term expansion of CD34+ cells and qualification of the resulting CD34+ population as advanced therapy medicinal product (ATMP)‐starting material. Among 20 639 licensed Düsseldorf cord blood units (CBUs), 139 potential HLA‐h donors were identified with the most frequent 10 German haplotypes. 100% of the donors were contacted, and for 47·5%, consent was obtained. HLA‐A, ‐B, ‐C, ‐DR, ‐DQ and ‐DP were determined by sequencing.

Methods

Thawing/washing of the CBUs was performed in the presence of Volulyte/HSA with Sepax®, CD34+ selection by automated CliniMACS®‐system (Miltenyi), expansion with qualified GMP‐grade cytokines and media in the GMP facility.

Results

Here, we specify minimal criteria (≥5 x 105 viable CD34+‐count, ≥80% CD34+‐purity and ≥70% viability) and confirm that n = 10 CB units (max storage time 16 years) could be qualified for an ATMP starting material. The mean fold change expansion of isolated CD34+ cells at Day 3/4 (d3/4) was 3·38 ± 3·02 with a mean purity of 86·90 ± 10·38% and a high viability of 96·07 ± 4·72%.

Conclusion

As of March 2019, approval was obtained by the Bezirksregierung Düsseldorf for the GMP‐compliant production. The production of HLA‐homozygous expanded CD34+ cells from cryopreserved CB under European ATMP regulations presented here describes the successful clinical translation and implementation of a qualified manufacturing process. This approach considers the main obstacle of rejection of transplanted cells (due to the immunological HLA barrier) by preselection of HLA‐homozygous transplants.
Research-based College English Blended Teaching of Fashion Major: A Case Study of Beijing Institute of Fashion Technology
Authors: Zi Weili , Zhou Yiling
Published: July 2020

With the further development of “the reform and open”, and the strategically stable advancement of “going out”, there is increasingly demand for foreign language talents and foreign language education. Research-based College English Blended Teaching just adapts to the national demand for international fashion talents with the international vision and the ability to participate in the international competition, which also provides us with opportunity to integrate the information technology with subject teaching. With the A-level class of grade 2018 from Beijing Institute of Fashion Technology (BIFT) as the case, the blended teaching theory as the guidance, this research presents the way of practice in research-based college English blended teaching by making use of the instrumental features of college English with the aim of cultivating students' professional research ability and academic communication ability. The study shows that remarkable results have been achieved in research-based blended teaching after three-semester practice-students could independently deliver academic presentation and conduct research in English individually or collaboratively in the professional field. The practice and exploration of the efficiency in research-based College English blended teaching could enhance the ability of academic presentation and academic writing of fashion majors, and promote their academic achievements for high-quality international fashion talents. Therefore, research-based College English blended teaching, integrating English skills with professional knowledge, is proved to be definitely instructive, implicational and exemplary to reform college English teaching in fashion field.
An
Alphavirus
-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates
Authors: Erasmus Jesse H. , Khandhar Amit P. , O’Connor Megan A. , Walls Alexandra C. , Hemann Emily A. , Murapa Patience , Archer Jacob , Leventhal Shanna , Fuller James T. , Lewis Thomas B. , Draves Kevin E. , Randall Samantha , Guerriero Kathryn A. , Duthie Malcolm S. , Carter Darrick , Reed Steven G. , Hawman David W. , Feldmann Heinz , Gale Michael , Veesler David , Berglund Peter , Fuller Deborah Heydenburg
Published: July 2020

Replicating RNA vaccine delivered by lipid inorganic nanoparticles induces neutralizing antibody and T cells against SARS-CoV-2 in mice and macaques.
Performance Evaluation of the Novodiag Bacterial GE+ Multiplex PCR Assay
Authors: Roy Charly , Robert David , Bénéjat Lucie , Buissonnière Alice , Ducournau Astrid , Mégraud Francis , Bessède Emilie , Boraud Delphine , Lehours Philippe
Published: July 2020

The bacteriological diagnosis of intestinal bacterial infections has historically been based on culture on agar plates. However, culture may lack sensitivity, and some enteropathogens, such as pathovars of
Escherichia coli
, may escape routine diagnosis. Our goal was to evaluate the analytical performance of the Novodiag Bacterial GE+ kit for the detection of enteropathogenic bacteria in acute community diarrhea. We included 251 stools in this study (198 retrospective and 53 prospective).
N-Linked Glycan Sites on the Influenza A Virus Neuraminidase Head Domain Are Required for Efficient Viral Incorporation and Replication
Authors: Östbye Henrik , Gao Jin , Martinez Mira Rakic , Wang Hao , de Gier Jan-Willem , Daniels Robert
Published: July 2020

N-linked glycans are transferred to secretory proteins upon entry into the endoplasmic reticulum lumen. In addition to promoting secretory protein maturation, enveloped viruses also utilize these large oligosaccharide structures to prevent access to surface antigen epitopes. Sequence analyses of the influenza A virus (IAV) surface antigen neuraminidase (NA or N) showed that the conservation of N-linked glycosylation sites on the NA enzymatic head domain differs by IAV subtype (H1N1 versus H3N2) and species of origin, with human-derived IAVs possessing the most variability. Experimental analyses verified that the N-linked glycosylation sites on the NA head domain contribute to virion incorporation and replication. It also revealed that the head domain glycans affect N1 stability more than N2, suggesting N2 is more accommodating to glycan additions. These results demonstrate that in addition to antigenicity, changes in N-linked glycosylation sites can alter other properties of viral surface antigens and virions.
T4 Pili Promote Colonization and Immune Evasion Phenotypes of Nonencapsulated M4 Streptococcus pyogenes
Authors: Chen Yi-Hsuan , Li Shao-Hui , Yang Yao-Cheng , Hsu Shu-Hao , Nizet Victor , Chang Yung-Chi
Published: July 2020

Group AStreptococcus(GAS) is a strict human pathogen causing more than 700 million infections globally each year. The majority of the disease-causing GAS are encapsulated, which greatly guarantees survival and dissemination in the host. Emergence of the capsule-negative GAS, such as M4 GAS, in recent epidemiologic surveillance alarms the necessity to elucidate the virulence determinants of these pathogens. Here, we found that M4 pili play an important role in promoting M4 GAS adherence and cytotoxicity to human pharyngeal epithelial cells and keratinocytes. The same molecule also significantly enhanced M4 GAS survival and replication in human whole blood and experimental murine infection. T4 antigen, which composes the backbone of M4 pili, was able to sequester the very abundant serum protein haptoglobin to further confer M4 GAS resistance to antibacterial substances released by neutrophils and platelets.
Discovery and Genomic Characterization of a 382-Nucleotide Deletion in ORF7b and ORF8 during the Early Evolution of SARS-CoV-2
Authors: Su Yvonne C. F. , Anderson Danielle E. , Young Barnaby E. , Linster Martin , Zhu Feng , Jayakumar Jayanthi , Zhuang Yan , Kalimuddin Shirin , Low Jenny G. H. , Tan Chee Wah , Chia Wan Ni , Mak Tze Minn , Octavia Sophie , Chavatte Jean-Marc , Lee Raphael T. C. , Pada Surinder , Tan Seow Yen , Sun Louisa , Yan Gabriel Z. , Maurer-Stroh Sebastian , Mendenhall Ian H. , Leo Yee-Sin , Lye David Chien , Wang Lin-Fa , Smith Gavin J. D.
Published: July 2020

During the SARS epidemic in 2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and eventually deletion variants became predominant, leading to the hypothesis that ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However, due to the successful control of the SARS epidemic, the importance of these deletions for the epidemiological fitness of SARS-CoV in humans could not be established. The emergence of multiple SARS-CoV-2 strains with ORF8 deletions, combined with evidence of a robust immune response to ORF8, suggests that the lack of ORF8 may assist with host immune evasion. In addition to providing a key insight into the evolutionary behavior of SARS-CoV-2 as the virus adapts to its new human hosts, the emergence of ORF8 deletion variants may also impact vaccination strategies.
Human Infection Challenge Studies: a Test for the Social Value Criterion of Research Ethics
Authors: Evans Nicholas G.
Published: July 2020

Human infection challenge studies involving the intentional infection of research participants with a disease-causing agent have recently been suggested as a means to speed up the search for a vaccine for the ongoing coronavirus disease 2019 (COVID-19) outbreak. Calls for challenge studies, however, rely on the expected social value of these studies. This value represents more than the simple possibility that a successful study will lead to the rapid development and dissemination of vaccines but also some expectation that this will actually occur.
Cardiac-associated biliary atresia (CABA): a prognostic subgroup
Authors: Aldeiri Bashar , Giamouris Vangelis , Pushparajah Kuberan , Miller Owen , Baker Alastair , Davenport Mark
Published: July 2020

Objectives

To describe the range of concurrent cardiac malformations in biliary atresia (BA) while providing a functional framework of risk.

Methods

Demographic and variables were collected from a prospectively maintained single-centre database. Infants were grouped according to a cardiac functional framework (A=acyanotic, B=cyanotic and C=insignificant shunt). Primary outcome was set as clearance of jaundice (bilirubin ≤20 μmol/L) following Kasai portoenterostomy (KPE). Native liver survival and overall actuarial survival were compared with a date-matched control infant with BA (n=77). P value <0.05 was regarded as significant.

Results

524 infants with histologically confirmed BA were treated between January 1999 and December 2018, 37 (7%) had a concurrent cardiac anomaly (A: n=23 (62%), B: n=10 (27%), C: n=4 (11%)). Infants with biliary atresia splenic malformation (BASM) or cat-eye syndrome (CES) contributed over half of the cases (21/37; 57%).

Overall, 20 (54%) infants cleared jaundice (vs 50/77 (65%) controls; p=0.2), but with higher mortality compared with the non-cardiac controls (15/37 (40%) vs 3/77 (4%); HR 15.5 (95% CI 5.5 to 43.4); p<0.00001). Infants requiring cardiac intervention in the first year of life (n=15) were more likely to clear jaundice (6/7 vs 2/8; p=0.04) and had a trend towards higher survival (6/7 vs 3/8; p=0.1) when KPE followed cardiac surgery. Yet, the type of cardiac pathology did not impact clearance of jaundice or mortality.

Conclusion

We propose the term cardiac-associated biliary atresia (CABA) as a high-risk group. We believe that restorative cardiac surgery should precede KPE wherever possible to improve outcome.
Novel patient-specific 3D-virtual reality visualisation software (SpectoVR) for the planning of spine surgery: a case series of eight patients
Authors: Croci Davide Marco , Guzman Raphael , Netzer Cordula , Mariani Luigi , Schaeren Stefan , Cattin Philippe C , Jost Gregory F
Published: July 2020

Background

Complex spine surgery requires a sound three-dimensional (3D) understanding of anatomy.

Objective

Here, we report the preoperative use a of novel software (SpectoVR) that presents DICOM data as virtual 3D holograms.

Methods

The software SpectoVR uses patient-specific DICOM data to render the anatomy as a hologram that is then viewed with a virtual reality (VR) headset. The surgeons used SpectoVR to prepare for complex surgeries.

Results

Eight patients with the following diagnosis were presurgically studied with SpectoVR: (1) ankylosing spondylitis with fixed kyphotic cervical deformity treated with osteotomy reduction and cervicothoracic reconstruction; (2) persistent cervical foraminal stenosis after total disc replacement; (3) atlantoaxial osteoarthritis treated with C1–2 Magerl fixation; (4) adjacent segment degeneration with foraminal stenosis L5–S1; (5) C2–C4 chordoma; (6) spinal cord injury with rotational thoracolumbar fracture; (7) complex lumbopelvic deformity after prior hemipelvectomy for sarcoma and (8) atlantoaxial osteoarthritis and basilar impression in a patient with congenital craniosynostosis. Whereas VR did not omit the need for viewing the spine in the multiplane reconstruction mode, the authors feel that SpectoVR contributed to a better holistic understanding of the anatomy. Furthermore, positioning the spine like in the OR empowered the mental preparation for the surgery.

Conclusion

Integrating SpectoVR in daily presurgical planning is feasible and appears to enhance the surgeon’s awareness of the case.
Development of a core outcome set for studies on prevention and management of pregnancy-associated venous thromboembolism (COSPVenTE): a study protocol
Authors: King Alexandria , D’Souza Rohan , Teshler Lizabeth , Shehata Nadine , Malinowski Ann K
Published: July 2020

Introduction

Pregnancy and post partum are times of heightened risk for the development of venous thromboembolism (VTE), which in turn is one of the leading causes of maternal mortality and long-term morbidity. The current research aimed at improving health guidelines for women with pregnancy-associated VTE is limited by inconsistency in outcome reporting preventing comparison across studies, and lack of input from patients with respect to outcomes they propose are most important to measure. A suggested solution is the development of a core outcome set (COS) that defines the minimum criteria for outcome reporting in clinical trials and prospective studies. COSs function to facilitate data harmonisation and increase homogeneity in outcome reporting while incorporating the voice of women in this population in the planning of research to inform their ongoing care.

Methods and analysis

The development of a COS for studies on pregnancy-associated VTE will comprise five steps. First, a systematic review of the published literature will identify currently reported outcomes, their definitions and measurements if applicable. This will be followed by in-person interviews with patients, clinicians, researchers, hospital administrators and policy-makers to identify outcomes they consider important. Third, the long list of outcomes obtained from steps I and II will be condensed through online Delphi surveys involving an international group of relevant stakeholders including patients. This will be followed by a face-to-face consensus meeting with representatives of all stakeholder groups to arrive at a consensus on the final COS. Lastly, to determine how the identified core outcomes should be measured, another literature review and Delphi process will be carried out as necessary.

Ethics and dissemination

This study has been approved by the Mount Sinai Hospital Research Ethics Board (REB 18-0314-E). Study results will be published in open-access journals and presented at obstetrics, maternal–fetal medicine and haematology conferences. All progress will be documented on the international prospective register of systematic reviews (PROSPERO) and Core Outcome Measures in Effectiveness Trials databases.

PROSPERO registration number

CRD42019111479.
Core outcome set for studies on pregnant women with vasa previa (COVasP): a study protocol
Authors: D’Souza Rohan , Villani Linda , Hall Chelsea , Seyoum Meron , Kingdom John , Krznaric Michael , Donnolley Natasha , Javid Nasrin
Published: July 2020

Introduction

Vasa previa is a condition where fetal blood vessels run unprotected in the membranes, outside the umbilical cord, and cross the internal opening of the cervix. During rupture of membranes, these vessels can rupture and put the baby at serious risk of severe blood loss and death. Numerous studies are being conducted to improve diagnostic modalities and establish clear management plans to improve pregnancy outcomes. However, the lack of a standardised set of outcomes for studies on vasa previa makes it difficult to compare study findings and draw meaningful conclusions. Through this project, we will be developing a core outcome set for studies on pregnant women with vasa previa (COVasP).

Methods and analysis

The development of COVasP will involve five steps. The first will be a systematic review, in which we will generate a long list of outcomes based on published studies in pregnancies complicated with vasa previa. The second will involve in-depth interviews with current and former patients, their family members and healthcare providers who care for these patients. This will be followed by a two-round Delphi survey, which will aim to narrow down the long list of outcomes into those considered important by four groups of ‘stakeholders’: (1) patients, family members and patient advocates/representatives, (2) healthcare providers, (3) researchers, epidemiologists and methodologists and (4) other stakeholders directly or indirectly involved in the management of these pregnancies such as administrators, guideline developers and policymakers. The fourth step will involve a face-to-face consensus meeting using a nominal group approach to establish a finalised core outcome set. The final step will involve measuring and defining the identified outcomes using a combination of systematic reviews and Delphi surveys.

Ethics and dissemination

This study as well as consent forms for stakeholder participation have received approval from the Mount Sinai Hospital Research Ethics Board (REB number 18-0173-E) on 05 September 2018 and the Human Research Ethics Committee at The University of Technology Sydney, Australia on 30 July 2019 (UTS HREC reference number ETH19-3718). All progress will be documented on the international prospective register of systematic reviews and Core Outcome Measures in Effectiveness Trials databases.

Registration details

http://www.comet-initiative.org/studies/details/1117.
Effect of an innovative behavioural change strategy and small-quantity lipid-based nutrient supplements on stunting and obesity in children in Baja Verapaz, Guatemala: protocol for a randomised control trial
Authors: González Acero Carolina , Martinez Sebastian , Pérez-Expósito Ana , Winters Solis
Published: July 2020

Introduction

In Latin America, a rapid increase in obesity alongside persistent malnutrition has resulted in a double burden of disease that affects the most vulnerable segments of the population. Infant and young child feeding practices are important factors that affect both sides of the growth curve. Interventions such as behavioural change strategies and home fortification using products like small-quantity lipid-based nutrient supplements (SQ-LNS) have the potential to reduce the presence of both these conditions, especially if they are implemented during the first 1000 days of life. This paper details the protocol for SPOON: Sustained Programme for Improving Nutrition, an innovative strategy to prevent stunting and reduce risk for obesity in children under 24 months old in high-poverty areas in Baja Verapaz, Guatemala.

Methods and analysis

SPOON: Sustained Programme for Improving Nutrition Guatemala is a three-arm randomised control trial: treatment group 1 will receive the programme behavioural change strategy and SQ-LNS, treatment group 2 will receive the programme behavioural change strategy and micronutrient powders; the control group will receive the standard of care provided by the Ministry of Health, which includes micronutrient powders. A modified formula of SQ-LNS has been especially developed for this trial. A total of 76 communities are included in the study and 1628 households with a pregnant woman in the third trimester or a child under 4.5 months were recruited at baseline. Baseline data were collected between September and November 2018. Follow-up data will be collected 2 years after the start of the intervention. The primary outcomes of interest are related to mothers’ infant feeding knowledge and practice, and indicators of children’s nutritional status and growth including height, weight, weight gain rate and prevalence of stunting, overweight, obesity and anaemia. After follow-up data have been collected, differences of simple means and regression models including covariates such as child’s age and sex, characteristics of the primary caregiver and household socioeconomic indicators will be estimated. Heterogeneous effects will also be estimated within subgroups of age at exposure, sex, caregiver characteristics and household socioeconomic status.

Ethics and dissemination

This study was approved by the National Health Ethics Committee of the Ministry of Health of Guatemala (resolution 10–2018). Informed consent was obtained from all mothers and caregivers prior to enrolment in the programme. Results will be submitted to a peer-reviewed medical or public health journal, and disseminated internally at the Inter-American Development Bank, with the Government and Stakeholders in Guatemala and through international conferences and seminars.

Trial registration number

NCT03399617
Estimation of total cardiovascular risk using the 2019 WHO CVD prediction charts and comparison of population-level costs based on alternative drug therapy guidelines: a population-based study of adults in Bangladesh
Authors: Islam Jessica Yasmine , Zaman M Mostafa , Moniruzzaman Mohammad , Ara Shakoor Shawkat , Hossain A H M Enayet
Published: July 2020

Objective

The objective of this study was to estimate the population distribution of 10-year cardiovascular disease (CVD) risk among Bangladeshi adults aged 40 years and above, using the 2019 WHO CVD risk prediction charts. Additionally, we compared the cost of CVD pharmacological treatment based on the total CVD risk (thresholds ≥30%/≥20%) and the single risk factor (hypertension) cut-off levels in the Bangladeshi context.

Study design

Cross-sectional, population-based study.

Setting and participants

From 2013 to 2014, we collected data from a nationally representative cross-sectional survey of adults aged ≥40 years from urban and rural areas of Bangladesh (n=6189). We estimated CVD risk using the 2019 WHO CVD risk prediction charts and categorised as very low (<5%), low (5% to <10%), moderate (10% to <20%), high (20% to <30%) and very high risk (≥30%). We estimated drug therapy costs using the lowest price of each drug class available (aspirin, thiazide diuretics, statins and ACE inhibitors). We compared the total cost of drug therapy using the total CVD risk versus single risk factor approach.

Primary outcome measures

Our primary outcome was 10-year CVD risk categorised as very low (<5%), low (5% to <10%), moderate (10% to <20%), high (20% to <30%) and very high risk (≥30%).

Results

The majority of adults (85.2%, 95% CI 84.3 to 86.1) have a 10-year CVD risk of less than 10%. The proportion of adults with a 10-year CVD risk of ≥20% was 0.51%. Only one adult was categorised with a 10-year CVD risk of ≥30%. Among adults with CVD risk groups of very low, low and moderate, 17.4%, 27.9% and 41.4% had hypertension (blood pressure (BP) ≥140/90) and 0.1%, 1.7% and 2.9% had severe hypertension (BP ≥160/100), respectively. Using the total CVD risk approach would reduce drug costs per million populations to US$144 540 (risk of ≥20%).

Conclusion

To reduce healthcare expenditure for the prevention and treatment of CVD, a total risk approach using the 2019 WHO CVD risk prediction charts may lead to cost savings.
HIV and other STIs self-testing to reduce risk compensation among men who have sex with men who use oral pre-exposure prophylaxis in China: protocol for a randomised waitlist-controlled trial
Authors: Zhang Jing , Huang Xiaojie , Chen Yaokai , Wang Hui , Zhang Yonghui , Wang Hongyi , Mei Zhu , Jia Yueru , Chu ZhenXing , Hu Qing-Hai , He Xiaoqing , Zhang Lukun , Hu Zhili , Bao Rantong , Li Shangcao , Ding Haibo , Jiang Yongjun , Geng Wenqing , Tang Weiming , Xu Junjie
Published: July 2020

Introduction

Pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection among men who have sex with men by up to 99%. However, in real-world settings, PrEP users may exhibit risk compensation after uptake of PrEP, including more condomless anal intercourse (CAI) and increased sexually transmitted infection (STI) acquisition. HIV self-testing (HIVST) decreases CAI among men who have sex with men (MSM) by providing awareness of the HIV status of oneself and one’s sexual partners. Here, we describe the rationale and design of a randomised waitlist-controlled trial to examine the impact of HIVST on risk compensation among PrEP users.

Methods and analysis

The study is a two-arm randomised waitlist-controlled trial with 1000 HIV-negative MSM in four major cities in China who will be taking oral PrEP (involving tenofovir disoproxil fumarate/emtricitabine) either daily (n=500) or in an event-driven regimen (n=500). The participants will be randomised (1:1) to either the immediate HIVST intervention arm (HIVST plus standard facility-based counselling and testing from 0 to 12 months) or the waitlist arm (standard facility-based counselling and testing from 0 to 6 months, then crossover to receive the HIVST intervention in months 7–12). Participants will provide blood samples to assess the incidence of syphilis and herpes simplex virus type 2 (HSV-2) during a follow-up. The primary outcomes will be the occurrence of CAI, number of sexual partners and incidence of syphilis and HSV-2 during a follow-up. The secondary outcomes will be the HIV and STI testing frequency and STI treatment adherence during a follow-up. The planned start and end dates for the study is 26 December 2018 and 31 December 2020.

Ethics and dissemination

The Medical Science Research Ethics Committee of The First Affiliated Hospital of China Medical University has approved the study (IRB(2018)273).

Trial registration number

ChiCTR1800020374
How well are sepsis and a sense of urgency documented throughout the acute care chain in the Netherlands? A prospective, observational study
Authors: Latten Gideon , Hensgens Kirsten , de Bont Eefje G P M , Muris Jean W M , Cals Jochen W L , Stassen Patricia
Published: July 2020

Objective

To investigate the documentation of sepsis and a sense of urgency throughout the acute care chain.

Design

Prospective cohort study.

Setting

Emergency department (ED) in a large district hospital in Heerlen, The Netherlands.

Participants

Participants included patients ≥18 years with suspected sepsis who visited the ED during out-of-hours between September 2017 and January 2018 (n=339) and had been referred by a general practitioner and/or transported by ambulance. We defined suspected sepsis as suspected or proven infection and the presence of ≥2 quick Sepsis-related Organ Failure Assessment and/or ≥2 Systemic Inflammatory Response Syndrome criteria.

Outcome measures

We analysed how often sepsis and a sense of urgency were documented in the prehospital and ED medical records. A sense of urgency was considered documented when a medical record suggested the need of immediate assessment by a physician in the ED. We described documentation patterns throughout the acute care chain and investigated whether documentation of sepsis or a sense of urgency is associated with adverse outcomes (intensive care admission/30-day all-cause mortality).

Results

Sepsis was documented in 16.8% of medical records and a sense of urgency in 22.4%. In 4.1% and 7.7%, respectively, sepsis and a sense of urgency were documented by all involved professionals. In patients with an adverse outcome, sepsis was documented more often in the ED than in patients without an adverse outcome (47.9% vs 13.7%, p<0.001).

Conclusions

Our study shows that in prehospital and ED medical records, sepsis and a sense of urgency are documented in one out of five patients. In only 1 out of 20 patients sepsis or a sense of urgency is documented by all involved professionals. It is possible that poor documentation causes harm, due to delayed diagnosis or treatment. Hence, it could be important to raise awareness among professionals regarding the importance of their documentation.
Person-centred care by a combined digital platform and structured telephone support for people with chronic obstructive pulmonary disease and/or chronic heart failure: study protocol for the PROTECT randomised controlled trial
Authors: Ali Lilas , Wallström Sara , Barenfeld Emmelie , Fors Andreas , Fredholm Eva , Gyllensten Hanna , Swedberg Karl , Ekman Inger
Published: July 2020

Background

A core feature of chronic obstructive pulmonary disorder (COPD) and chronic heart failure (CHF) is that symptoms may change rapidly because of illness progression. Thus, these chronic conditions are associated with high rehospitalisation rates. Person-centred care (PCC) has been shown to have several benefits for patients with COPD or CHF (or both disorders) but it has not yet been investigated through e-health services.

Aim

The project aims to evaluate the effects of PCC by a combined digital platform and structured telephone support for people with COPD and/or CHF.

Methods and analysis

A randomised controlled trial with open, parallel groups which employs a participatory design process will be used. This project will also include process and health economic evaluation of the intervention.

Ethics and dissemination

Ethical approval has been secured from the Regional Ethical Review Board in Gothenburg, Sweden (Dnr 063-17 and T063-18). Results will be presented at conferences and to healthcare professionals, participants and patient organisations. Findings will also be submitted for publication in peer-reviewed journals.

Trial registration number

NCT03183817
Study protocol for a 9-month randomised controlled trial assessing the effects of almonds versus carbohydrate-rich snack foods on weight loss and weight maintenance
Authors: Carter Sharayah , Hill Alison M , Yandell Catherine , Buckley Jonathan D , Tan Sze-Yen , Rogers Geraint B , Childs Jessie , Matheson Mark , Lamb Kate , Ward Susan , Stanton Tasha R , Fraysse Francois , Hills Andrew P , Coates Alison M
Published: July 2020

Introduction

Epidemiological studies indicate an inverse association between nut consumption and body mass index (BMI). However, clinical trials evaluating the effects of nut consumption compared with a nut-free diet on adiposity have reported mixed findings with some studies reporting greater weight loss and others reporting no weight change. This paper describes the rationale and detailed protocol for a randomised controlled trial assessing whether the inclusion of almonds or carbohydrate-rich snacks in an otherwise nut-free energy-restricted diet will promote weight loss during 3 months of energy restriction and limit weight regain during 6 months of weight maintenance.

Methods and analysis

One hundred and thirty-four adults aged 25–65 years with a BMI of 27.5–34.9 kg/m2will be recruited and randomly allocated to either the almond-enriched diet (AED) (15% energy from almonds) or a nut-free control diet (NFD) (15% energy from carbohydrate-rich snack foods). Study snack foods will be provided. Weight loss will be achieved through a 30% energy restriction over 3 months, and weight maintenance will be encouraged for 6 months by increasing overall energy intake by ~120–180 kcal/day (~500-750kJ/day) as required. Food will be self-selected, based on recommendations from the study dietitian. Body composition, resting energy expenditure, total daily energy expenditure (via doubly labelled water), physical activity, appetite regulation, cardiometabolic health, gut microbiome, liver health, inflammatory factors, eating behaviours, mood and personality, functional mobility and pain, quality of life and sleep patterns will be measured throughout the 9-month trial. The effects of intervention on the outcome measures over time will be analysed using random effects mixed models, with treatment (AED or NFD) and time (baseline, 3 months and 9 months) being the between and within factors, respectively in the analysis.

Ethics and dissemination

Ethics approval was obtained from the University of South Australia Human Research Ethics Committee (201436). Results from this trial will be disseminated through publication in peer-reviewed journals, national and international presentations.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12618001861246).
Associations of grip strength with retinal and choroidal thickness in patients with type 2 diabetes mellitus without retinopathy: a cross-sectional study
Authors: Qiu Zihan , Wang Wei , Tan Yan , He Miao , Wang Langhua , Li Yuting , Gong Xia , Huang Wenyong
Published: July 2020

Objective

To evaluate the associations of grip strength with retinal or choroidal thickness in patients with type 2 diabetes mellitus without retinopathy.

Design

Observational study-cross-sectional design.

Setting and participants

This study included the Chinese patients with type 2 diabetes without retinopathy registered in the community health system in Guangzhou, China.

Measures

The grip strength in both hands were measured by using a dynamometer. The retinal and choroidal thickness in macular region stratified by Early Treatment Diabetic Retinopathy Study (ETDRS) sectors were measured by a swept-source optical coherence tomography.

Results

A total of 1029 patients were included. Both retinal thickness and choroidal thickness decreased with the lower quartile of grip strength. Regression analyses indicated that the average retinal and choroidal thickness increased by 0.14 µm (95% CI: 0.03 to 0.25 µm, p=0.011) and 0.57 µm (95% CI: 0.03 to 1.11 µm, p=0.037), respectively, for each additional kilogram of grip strength following adjustment for age and sex. Further adjustments were made for axial length, haemoglobin A1c, length of time the patient had diabetes, insulin usage, height, weight and systolic and diastolic blood pressure, which resulted in an average retinal and choroidal thickness increase of 0.13 µm (95% CI: 0.02 to 0.24 µm, p=0.024) and 0.65 µm (95% CI: 0.13 to 1.16 µm, p=0.013), respectively, for each additional kilogram of grip strength. Consistent results were obtained in the analyses in ETDRS 9 sectors.

Conclusion

Lower hand grip strength was found to be significantly associated with thinner retinal and choroidal layers in patients with diabetes. Grip strength may provide a useful and easily administered indicator of retinal status in patients with diabetes.
Neutrophil–lymphocyte ratio across psychiatric diagnoses: a cross-sectional study using electronic health records
Authors: Brinn Aimee , Stone James
Published: July 2020

Objectives

The main objective of this study was to compare neutrophil–lymphocyte ratio (NLR), a marker of systemic inflammation, between patients diagnosed with International Classification of Diseases 10th Revision (ICD-10) psychiatric disorders and control participants.

Design

A cross-sectional methodology was employed to retrospectively analyse electronic health records and records derived from a national health survey.

Setting

A secondary mental healthcare service consisting of four boroughs in South London.

Participants

A diverse sample of 13 888 psychiatric patients extracted from South London and Maudsley electronic health records database and 3920 control participants extracted from National Health and Nutrition Survey (2015–2016) were included in the study.

Primary and secondary outcome measures

Primary: NLR levels in patients with mental health diagnoses, NLR between patients with different mental health diagnoses. Secondary: relationship of NLR to length of hospitalisation and to mortality.

Results

NLR was elevated compared with controls in patients with diagnoses including dementia, alcohol dependence, schizophrenia, bipolar affective disorder, depression, non-phobic anxiety disorders and mild mental retardation (p<0.05). NLR also correlated with age, antipsychotic use and hypnotic use. NLR was found to be higher in individuals of ‘white’ ethnicity and lower in individuals of ‘black’ ethnicity. Elevated NLR was associated with increased mortality (β=0.103, p=2.9e−08) but not with hospital admissions or face-to-face contacts.

Conclusions

Elevated NLR may reflect a transdiagnostic pathological process occurring in a subpopulation of psychiatric patients. NLR may be useful to identify and stratify patients who could benefit from adjunctive anti-inflammatory treatment.
Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit
Authors: Azimaraghi Omid , Hammer Maximilian , Santer Peter , Platzbecker Katharina , Althoff Friederike C , Patrocinio Maria , Grabitz Stephanie D , Wongtangman Karuna , Rumyantsev Sandra , Xu Xinling , Schaefer Maximilian S , Fuller Patrick M , Subramaniam Balachundhar , Eikermann Matthias
Published: July 2020

Introduction

Insomnia frequently occurs in patients admitted to an intensive care unit (ICU). Sleep-promoting agents may reduce rapid eye movement sleep and have deliriogenic effects. Suvorexant (Belsomra) is an orexin receptor antagonist with Food and Drug Administration (FDA) approval for the treatment of adult insomnia, which improves sleep onset and maintenance as well as subjective measures of quality of sleep. This trial will evaluate the efficacy of postoperative oral suvorexant treatment on night-time wakefulness after persistent sleep onset as well as the incidence and duration of delirium among adult cardiac surgical patients.

Methods and analysis

In this single-centre, randomised, double-blind, placebo-controlled trial, we will enrol 120 patients, aged 60 years or older, undergoing elective cardiac surgery with planned postoperative admission to the ICU. Participants will be randomised to receive oral suvorexant (20 mg) or placebo one time a day starting the night after extubation. The primary outcome will be wakefulness after persistent sleep onset. The secondary outcome will be total sleep time. Exploratory outcomes will include time to sleep onset, incidence of postoperative in-hospital delirium, number of delirium-free days and subjective sleep quality.

Ethics and dissemination

Ethics approval was obtained through the ‘Committee on Clinical Investigations’ at Beth Israel Deaconess Medical Center (protocol number 2019P000759). The findings will be published in peer-reviewed journals.

Trial registration number

This trial has been registered at clinicaltrials.gov on 17 September 2019 (NCT04092894).
Cohort profile: BIOVASC-late, a prospective multicentred study of imaging and blood biomarkers of carotid plaque inflammation and risk of late vascular recurrence after non-severe stroke in Ireland
Authors: McCabe John Joseph , Giannotti Nicola , McNulty Jonathan , Collins Sean , Coveney Sarah , Murphy Sean , Barry Mary , Harbison Joseph , Cronin Simon , Williams David , Horgan Gillian , Dolan Eamon , Cassidy Tim , McDonnell Ciaran , Kavanagh Eoin , Foley Shane , O'Connell Martin , Marnane Michael , Kelly Peter
Published: July 2020

Purpose

Inflammation is important in stroke. Anti-inflammatory therapy reduces vascular events in coronary patients. 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) identifies plaque inflammation-related metabolism. However, long-term prospective cohort studies investigating the association between carotid plaque inflammation, identified on 18F-FDG PET and the risk of recurrent vascular events, have not yet been undertaken in patients with stroke.

Participants

The Biomarkers Imaging Vulnerable Atherosclerosis in Symptomatic Carotid disease (BIOVASC) study and Dublin Carotid Atherosclerosis Study (DUCASS) are two prospective multicentred observational cohort studies, employing near-identical methodologies, which recruited 285 patients between 2008 and 2016 with non-severe stroke/transient ischaemic attack and ipsilateral carotid stenosis (50%–99%). Patients underwent coregistered carotid 18F-FDG PET/CT angiography and phlebotomy for measurement of inflammatory cytokines. Plaque 18F-FDG-uptake is expressed as maximum standardised uptake value (SUVmax) and tissue-to-background ratio. The BIOVASC-Late study is a follow-up study (median 7 years) of patients recruited to the DUCASS/BIOVASC cohorts.

Findings to date

We have reported that 18F-FDG-uptake in atherosclerotic plaques of patients with symptomatic carotid stenosis predicts early recurrent stroke, independent of luminal narrowing. The incorporation of 18F-FDG plaque uptake into a clinical prediction model also improves discrimination of early recurrent stroke, when compared with risk stratification by luminal stenosis alone. However, the relationship between 18F-FDG-uptake and late vascular events has not been investigated to date.

Future plans

The primary aim of BIOVASC-Late is to investigate the association between SUVmax in symptomatic ‘culprit’ carotid plaque (as a marker of systemic inflammatory atherosclerosis) and the composite outcome of any late major vascular event (recurrent ischaemic stroke, coronary event or vascular death). Secondary aims are to investigate associations between: (1) SUVmax in symptomatic plaque, and individual vascular endpoints (2) SUVmax in asymptomatic contralateral carotid plaque and SUVmax in ipsilateral symptomatic plaque (3) SUVmax in asymptomatic carotid plaque and major vascular events (4) inflammatory cytokines and vascular events.
‘Did I pass the licensing exam?’ aspects influencing migrant physicians’ results: a mixed methods study
Authors: Sturesson Linda , Heiding Andreas , Olsson Daniel , Stenfors Terese
Published: July 2020

Objectives

Migrant physicians (MPs) who wish to practise their profession in a new country often must undergo a recertification process, including a licensing exam. In many cases, this is the same licensing exam used for peers educated within the country; however, the pass rate of MPs is usually lower. This study aimed to explore MPs exam results, focusing on MPs that had participated in a complementary programme (CPP) for physicians with a medical degree from outside the European Union/European Economic Area (EU/EEA), and aspects that may influence these.

Methods

Mixed methods were applied. The data consisted of 2013 to 2019 licensing exam results of 564 physicians in Sweden that were educated outside of the EU. The data was analysed using linear and logistic regression analysis. Further, 14 interviews with MPs were conducted and thematically analysed.

Results

An interaction between age and CPP participation was found for both the total score in per cent (p=0.01) and for the proportion failing their first attempt (p=0.04). Age was found to be a very strong predictor for failing on the first attempt, with those 45 and older failing on the first attempt in 72 and 82 per cent for CPP and non-CPP participants, respectively. Interview data was categorised into two themes: preparations and biographical aspects, and the exam and exam situation.

Conclusions

Age seems to be an important predictor for failing the first attempt. MPs have had less time to familiarise themselves with the exam type and the language used on the exam. To improve exam results, MPs used different strategies and tools, that is, studying with nationally trained physicians, and using old exams and a web-based study tool consisting of common exam subjects. At the same time, these strategies and tools have also become mediators in the socialisation of MPs into the exam context.
Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19
Authors: Zuo Tao , Liu Qin , Zhang Fen , Lui Grace Chung-Yan , Tso Eugene YK , Yeoh Yun Kit , Chen Zigui , Boon Siaw Shi , Chan Francis KL , Chan Paul KS , Ng Siew C
Published: July 2020

Objective

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19.

Design

We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity.

Results

Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3’ vs 5’ end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3’ vs 5’ end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species Collinsella aerofaciens, Collinsella tanakaei, Streptococcus infantis, Morganella morganii, and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, Parabacteroides merdae, Bacteroides stercoris, Alistipes onderdonkii and Lachnospiraceae bacterium 1_1_57FAA.

Conclusion

This pilot study provides evidence for active and prolonged ‘quiescent’ GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.