bluuebunny/crossref_metadata_2025 huggingface dataset:
Global record of “ghost” nannofossils reveals plankton resilience to high CO
2
and warming
Authors: Slater Sam M. , Bown Paul , Twitchett Richard J. , Danise Silvia , Vajda Vivi
Published: May 2022

Predictions of how marine calcifying organisms will respond to climate change rely heavily on the fossil record of nannoplankton. Declines in calcium carbonate (CaCO
3
) and nannofossil abundance through several past global warming events have been interpreted as biocalcification crises caused by ocean acidification and related factors. We present a global record of imprint—or “ghost”—nannofossils that contradicts this view, revealing exquisitely preserved nannoplankton throughout an inferred Jurassic biocalcification crisis. Imprints from two further Cretaceous warming events confirm that the fossil records of these intervals have been strongly distorted by CaCO
3
dissolution. Although the rapidity of present-day climate change exceeds the temporal resolution of most fossil records, complicating direct comparison with past warming events, our findings demonstrate that nannoplankton were more resilient to past events than traditional fossil evidence suggests.
Recognition of pathogen-derived sphingolipids in
Arabidopsis
Authors: Kato H. , Nemoto K. , Shimizu M. , Abe A. , Asai S. , Ishihama N. , Matsuoka S. , Daimon T. , Ojika M. , Kawakita K. , Onai K. , Shirasu K. , Yoshida M. , Ishiura M. , Takemoto D. , Takano Y. , Terauchi R.
Published: May 2022

In plants, many invading microbial pathogens are recognized by cell-surface pattern recognition receptors, which induce defense responses. Here, we show that the ceramide
Phytophthora infestans
–ceramide D (Pi-Cer D) from the plant pathogenic oomycete
P. infestans
triggers defense responses in
Arabidopsis
. Pi-Cer D is cleaved by an
Arabidopsis
apoplastic ceramidase, NEUTRAL CERAMIDASE 2 (NCER2), and the resulting 9-methyl–branched sphingoid base is recognized by a plasma membrane lectin receptor–like kinase, RESISTANT TO DFPM-INHIBITION OF ABSCISIC ACID SIGNALING 2 (RDA2). 9-Methyl–branched sphingoid base is specific to microbes and induces plant immune responses by physically interacting with RDA2. Loss of
RDA2
or
NCER2
function compromised
Arabidopsis
resistance against an oomycete pathogen. Thus, we elucidated the recognition mechanisms of pathogen-derived lipid molecules in plants.
Can internet use become addictive?
Authors: Brand Matthias
Published: May 2022

Problematic internet use parallels drug addiction, but the mechanisms are not yet clear
The forest forecast
Authors: Pearce Fred
Published: May 2022

Climate change could lead to a net expansion of global forests. But will a more forested world actually be cooler?
ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection
Authors: Karki Rajendra , Lee SangJoon , Mall Raghvendra , Pandian Nagakannan , Wang Yaqiu , Sharma Bhesh Raj , Malireddi RK Subbarao , Yang Dong , Trifkovic Sanja , Steele Jacob A. , Connelly Jon P. , Vishwanath Gella , Sasikala Mitnala , Reddy Duvvur Nageshwar , Vogel Peter , Pruett-Miller Shondra M. , Webby Richard , Jonsson Colleen Beth , Kanneganti Thirumala-Devi
Published: May 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), continues to cause substantial morbidity and mortality in the ongoing global pandemic. Understanding the fundamental mechanisms that govern innate immune and inflammatory responses during SARS-CoV-2 infection is critical for developing effective therapeutic strategies. Whereas interferon (IFN)–based therapies are generally expected to be beneficial during viral infection, clinical trials in COVID-19 have shown limited efficacy and potential detrimental effects of IFN treatment during SARS-CoV-2 infection. However, the underlying mechanisms responsible for this failure remain unknown. In this study, we found that IFN induced Z-DNA-binding protein 1 (ZBP1)–mediated inflammatory cell death, PANoptosis, in human and murine macrophages and in the lungs of mice infected with β-coronaviruses, including SARS-CoV-2 and mouse hepatitis virus (MHV). In patients with COVID-19, expression of the innate immune sensorZBP1was increased in immune cells from those who succumbed to the disease compared with those who recovered, further suggesting a link between ZBP1 and pathology. In mice, IFN-β treatment after β-coronavirus infection increased lethality, and genetic deletion ofZbp1or its Zα domain suppressed cell death and protected the mice from IFN-mediated lethality during β-coronavirus infection. Overall, our results identify that ZBP1 induced during coronavirus infection limits the efficacy of IFN therapy by driving inflammatory cell death and lethality. Therefore, inhibiting ZBP1 activity may improve the efficacy of IFN therapy, paving the way for the development of new and critically needed therapeutics for COVID-19 as well as other infections and inflammatory conditions where IFN-mediated cell death and pathology occur.
Visualization of mRNA Expression in Pseudomonas aeruginosa Aggregates Reveals Spatial Patterns of Fermentative and Denitrifying Metabolism
Authors: Livingston Jadzia , Spero Melanie A. , Lonergan Zachery R. , Newman Dianne K.
Published: May 2022

To understand bacteria in diverse contexts, we must understand the variations in behaviors and metabolisms they express spatiotemporally. Populations of bacteria are known to be heterogeneous, but the ways this variation manifests can be challenging to characterize due to technical limitations.
Gene-Based Diagnosis of Tuberculosis from Oral Swabs with a New Generation Pathogen Enrichment Technique
Authors: Kang Young Ae , Koo Bonhan , Kim Ock-Hwa , Park Joung Ha , Kim Ho Cheol , Lee Hyo Joo , Kim Myoung Gyu , Jang Youngwon , Kim Na Hyun , Koo Yong Seo , Shin Yong , Lee Sei Won , Kim Sung-Han
Published: May 2022

The development of a rapid, accessible, and highly sensitive diagnostic tool is a major challenge in the control and management of tuberculosis. Gene-based diagnostics is recommended for the rapid diagnosis of pulmonary tuberculosis (PTB), but its sensitivity, such as Xpert MTB/RIF assay (Xpert), drops in cases with a low bacterial load.
The
fruB
Gene of Streptococcus mutans Encodes an Endo-Levanase That Enhances Growth on Levan and Influences Global Gene Expression
Authors: Chakraborty Brinta , Zeng Lin , Burne Robert A.
Published: May 2022

Carbohydrate metabolism and acid production are essential for the development of dental caries. As a by-product of sucrose metabolism, formation, and degradation of fructans enhances the severity of caries by
S. mutans
in animal models.
Multiple Novel Ceftazidime-Avibactam-Resistant Variants of
bla
KPC-2
-Positive Klebsiella pneumoniae in Two Patients
Authors: Shi Qingyu , Han Renru , Guo Yan , Yang Yang , Wu Shi , Ding Li , Zhang Rong , Yin Dandan , Hu Fupin
Published: May 2022

Carbapenem-resistant
K. pneumoniae
which was classified as the most urgent threat by World Health Organization, is the most critical public health concern due to its high mortality rate. Recently, the rapid mutation of
bla
KPC
has occurred during anti-infective therapy, which posed an unexpected challenge for both the diagnostic laboratory and clinical practice.
Acute interstitial nephritis after COVID-19 vaccination
Authors: Tan Felicia SC , Kabir Mohammad E , Bhandari Sunil
Published: May 2022

A woman in her 70s presented to the hospital being generally unwell 8 days following the first dose of the AstraZeneca COVID-19 vaccination. She was in stage III acute kidney injury (AKI) with hyperkalaemia and metabolic acidosis. Urinalysis showed haematoproteinuria. Renal immunology screen was negative. She subsequently underwent two renal biopsies. The second biopsy showed features consistent with acute tubulointerstitial nephritis. She was commenced on oral steroids, which led to marked improvement of her renal function.

There are reasons why AKI can occur post vaccination such as prerenal AKI from reduced oral intake postvaccination due to feeling unwell or developing vomiting or diarrhoea. Intravenous fluids were given to this patient but with no meaningful improvement in renal function. She developed a possible reaction to the AstraZeneca COVID-19 vaccine, which led to AKI as supported by the interstitial inflammation and presence of eosinophils on renal biopsy.
Thrombosis within the left anterior descending coronary artery and left ventricle after high-dose nitrous oxide use
Authors: Kuipers Remko S , Paes Aron J , Amoroso Giovanni , Riezebos Robert K
Published: May 2022

We present a man in his 30s with acute anterior myocardial infarction due to thrombotic occlusion of the left anterior descending artery and subsequent left ventricular thrombus formation after high-dose recreational use of nitrous oxide (N2O). Initial questioning for use of illicit substances was negative, but low vitamin B12levels and severely elevated homocysteine levels prompted us to interrogate for the use of laughing gas. On questioning, the patient admitted to have used this substance, which he presumed to be innocent. Neither percutaneous coronary intervention with balloon dilatation nor intravenous glycoprotein IIb/IIIa receptor antagonist, nor continuous use of anticoagulation and double antiplatelet therapy resulted in thrombus resolution. Due to a severely reduced left ventricular function, despite 3 months on heart failure therapy, the patient is being counselled for intracardiac defibrillator implantation. We conclude that N2O, notably when consumed in conjunction with other proatherogenic substances, is associated with thrombosis: a relation possibly mediated by severe hyperhomocysteinaemia.
Cocaine-induced rhabdomyolysis and compartment syndrome
Authors: Iftikhar Mian Harris , Dar Aneeqa Yousaf , Haw Alexandra
Published: May 2022

A man in his 30s with a history of cocaine and intranasal heroin use presented to the emergency department with severe leg pain and weakness. Physical examination findings were significant for tachycardia, absence of dorsalis pedis pulses, tense and painful calf muscles along with absence of plantar reflexes in bilateral lower extremities. Laboratory investigations were significant for positive urinary drug screen for cocaine, severe rhabdomyolysis and acute kidney injury. Given the absence of dorsalis pedis pulses in bilateral lower extremities and radiological evidence of oedematous changes in calf muscles with perimuscular oedema, a diagnosis of compartment syndrome was made. He was treated with bilateral lower extremity four-compartment fasciotomies and haemodialysis for acute kidney injury. Rhabdomyolysis has been attributed to cocaine use; however, compartment syndrome is a very rare complication, especially in the absence of trauma or prolonged immobilisation.
Validity of data extraction in evidence synthesis practice of adverse events: reproducibility study
Authors: Xu Chang , Yu Tianqi , Furuya-Kanamori Luis , Lin Lifeng , Zorzela Liliane , Zhou Xiaoqin , Dai Hanming , Loke Yoon , Vohra Sunita
Published: May 2022

Objectives

To investigate the validity of data extraction in systematic reviews of adverse events, the effect of data extraction errors on the results, and to develop a classification framework for data extraction errors to support further methodological research.

Design

Reproducibility study.

Data sources

PubMed was searched for eligible systematic reviews published between 1 January 2015 and 1 January 2020. Metadata from the randomised controlled trials were extracted from the systematic reviews by four authors. The original data sources (eg, full text and ClinicalTrials.gov) were then referred to by the same authors to reproduce the data used in these meta-analyses.

Eligibility criteria for selecting studies

Systematic reviews were included when based on randomised controlled trials for healthcare interventions that reported safety as the exclusive outcome, with at least one pair meta-analysis that included five or more randomised controlled trials and with a 2×2 table of data for event counts and sample sizes in intervention and control arms available for each trial in the meta-analysis.

Main outcome measures

The primary outcome was data extraction errors summarised at three levels: study level, meta-analysis level, and systematic review level. The potential effect of such errors on the results was further investigated.

Results

201 systematic reviews and 829 pairwise meta-analyses involving 10 386 randomised controlled trials were included. Data extraction could not be reproduced in 1762 (17.0%) of 10 386 trials. In 554 (66.8%) of 829 meta-analyses, at least one randomised controlled trial had data extraction errors; 171 (85.1%) of 201 systematic reviews had at least one meta-analysis with data extraction errors. The most common types of data extraction errors were numerical errors (49.2%, 867/1762) and ambiguous errors (29.9%, 526/1762), mainly caused by ambiguous definitions of the outcomes. These categories were followed by three others: zero assumption errors, misidentification, and mismatching errors. The impact of these errors were analysed on 288 meta-analyses. Data extraction errors led to 10 (3.5%) of 288 meta-analyses changing the direction of the effect and 19 (6.6%) of 288 meta-analyses changing the significance of the P value. Meta-analyses that had two or more different types of errors were more susceptible to these changes than those with only one type of error (for moderate changes, 11 (28.2%) of 39v26 (10.4%) 249, P=0.002; for large changes, 5 (12.8%) of 39v8 (3.2%) of 249, P=0.01).

Conclusion

Systematic reviews of adverse events potentially have serious issues in terms of the reproducibility of the data extraction, and these errors can mislead the conclusions. Implementation guidelines are urgently required to help authors of future systematic reviews improve the validity of data extraction.
Public health impact of covid-19 vaccines in the US: observational study
Authors: Suthar Amitabh Bipin , Wang Jing , Seffren Victoria , Wiegand Ryan E , Griffing Sean , Zell Elizabeth
Published: May 2022

Objective

To evaluate the impact of vaccine scale-up on population level covid-19 mortality and incidence in the United States.

Design

Observational study.

Setting

US county level case surveillance and vaccine administration data reported from 14 December 2020 to 18 December 2021.

Participants

Residents of 2558 counties from 48 US states.

Main outcome measures

The primary outcome was county covid-19 mortality rates (deaths/100 000 population/county week). The secondary outcome was incidence of covid-19 (cases/100 000 population/county week). Incidence rate ratios were used to compare rates across vaccination coverage levels. The impact of a 10% improvement in county vaccination coverage (defined as at least one dose of a covid-19 vaccine among adults ≥18 years of age) was estimated During the eras of alpha and delta variant predominance, the impact of very low (0-9%), low (10-39%), medium (40-69%), and high (≥70%) vaccination coverage levels was compared.

Results

In total, 30 643 878 cases of covid-19 and 439 682 deaths associated with covid-19 occurred over 132 791 county weeks. A 10% improvement in vaccination coverage was associated with an 8% (95% confidence interval 8% to 9%) reduction in mortality rates and a 7% (6% to 8%) reduction in incidence. Higher vaccination coverage levels were associated with reduced mortality and incidence rates during the eras of alpha and delta variant predominance.

Conclusions

Higher vaccination coverage was associated with lower rates of population level covid-19 mortality and incidence in the US.
Long term impact of prophylactic antibiotic use before incision versus after cord clamping on children born by caesarean section: longitudinal study of UK electronic health records
Authors: Šumilo Dana , Nirantharakumar Krishnarajah , Willis Brian H , Rudge Gavin M , Martin James , Gokhale Krishna , Thayakaran Rasiah , Adderley Nicola J , Chandan Joht Singh , Okoth Kelvin , Harris Isobel M , Hewston Ruth , Skrybant Magdalena , Deeks Jonathan J , Brocklehurst Peter
Published: May 2022

Objective

To investigate the impact on child health up to age 5 years of a policy to use antibiotic prophylaxis for caesarean section before incision compared with after cord clamping.

Design

Observational controlled interrupted time series study.

Setting

UK primary and secondary care.

Participants

515 945 children born in 2006-18 with linked maternal records and registered with general practices contributing to two UK primary care databases (The Health Improvement Network and Clinical Practice Research Datalink), and 7 147 884 children with linked maternal records in the Hospital Episode Statistics database covering England, of which 3 945 351 were linked to hospitals that reported the year of policy change to administer prophylactic antibiotics for caesarean section before incision rather than after cord clamping.

Intervention

Fetal exposure to antibiotics shortly before birth (using pre-incision antibiotic policy as proxy) compared with no exposure.

Main outcome measures

The primary outcomes were incidence rate ratios of asthma and eczema in children born by caesarean section when pre-incision prophylactic antibiotics were recommended compared with those born when antibiotics were administered post-cord clamping, adjusted for temporal changes in the incidence rates in children born vaginally.

Results

Prophylactic antibiotics administered before incision for caesarean section compared with after cord clamping were not associated with a significantly higher risk of asthma (incidence rate ratio 0.91, 95% confidence interval 0.78 to 1.05) or eczema (0.98, 0.94 to 1.03), including asthma and eczema resulting in hospital admission (1.05, 0.99 to 1.11 and 0.96, 0.71 to 1.29, respectively), up to age 5 years.

Conclusions

This study found no evidence of an association between pre-incision prophylactic antibiotic use and risk of asthma and eczema in early childhood in children born by caesarean section.
Diagnosis and management of covid-19 in pregnancy
Authors: Nana Melanie , Hodson Kenneth , Lucas Nuala , Camporota Luigi , Knight Marian , Nelson-Piercy Cathy
Published: May 2022

Pregnant women with covid-19 are at greater risk of severe disease than their non-pregnant peers, and yet they are frequently denied investigations or treatments because of unfounded concerns about risk to the fetus. The basic principles of diagnosing and managing covid-19 are the same as for non-pregnant patients, and a multidisciplinary, expert team approach is essential to ensure optimal care. During pregnancy, treatment with corticosteroids should be modified to use non-fluorinated glucocorticoids. Il-6 inhibitors and monoclonal antibodies, together with specific antiviral therapies, may also be considered. Prophylaxis against venous thromboembolism is important. Women may require respiratory support with oxygen, non-invasive ventilation, ventilation in a prone position (either awake or during invasive ventilation), intubation and ventilation, and extracorporeal membrane oxygenation (ECMO). Pregnancy is not a contraindication for any of these supportive therapies, and the criteria for providing them are the same as in the general population. Decisions regarding timing, place, and mode of delivery should be taken with a multidisciplinary team including obstetricians, physicians, anesthetists, and intensivists experienced in the care of covid-19 in pregnancy. Ideally these decisions should take place in consultation with centers that have experience and expertise in all these specialties.
Impact of seasonal malaria chemoprevention on prevalence of malaria infection in malaria indicator surveys in Burkina Faso and Nigeria
Authors: de Cola Monica Anna , Sawadogo Benoît , Richardson Sol , Ibinaiye Taiwo , Traoré Adama , Compaoré Cheick Saïd , Oguoma Chibuzo , Oresanya Olusola , Tougri Gauthier , Rassi Christian , Roca-Feltrer Arantxa , Walker Patrick , Okell Lucy C
Published: May 2022

Background

In 2012, the WHO issued a policy recommendation for the use of seasonal malaria chemoprevention (SMC) to children 3–59 months in areas of highly seasonal malaria transmission. Clinical trials have found SMC to prevent around 75% of clinical malaria. Impact under routine programmatic conditions has been assessed during research studies but there is a need to identify sustainable methods to monitor impact using routinely collected data.

Methods

Data from Demographic Health Surveys were merged with rainfall, geographical and programme data in Burkina Faso (2010, 2014, 2017) and Nigeria (2010, 2015, 2018) to assess impact of SMC. We conducted mixed-effects logistic regression to predict presence of malaria infection in children aged 6–59 months (rapid diagnostic test (RDT) and microscopy, separately).

Results

We found strong evidence that SMC administration decreases odds of malaria measured by RDT during SMC programmes, after controlling for seasonal factors, age, sex, net use and other variables (Burkina Faso OR 0.28, 95% CI 0.21 to 0.37, p<0.001; Nigeria OR 0.40, 95% CI 0.30 to 0.55, p<0.001). The odds of malaria were lower up to 2 months post-SMC in Burkina Faso (1-month post-SMC: OR 0.29, 95% CI 0.12 to 0.72, p=0.01; 2 months post-SMC: OR: 0.33, 95% CI 0.17 to 0.64, p<0.001). The odds of malaria were lower up to 1 month post-SMC in Nigeria but was not statistically significant (1-month post-SMC 0.49, 95% CI 0.23 to 1.05, p=0.07). A similar but weaker effect was seen for microscopy (Burkina Faso OR 0.38, 95% CI 0.29 to 0.52, p<0.001; Nigeria OR 0.53, 95% CI 0.38 to 0.76, p<0.001).

Conclusions

Impact of SMC can be detected in reduced prevalence of malaria from data collected through household surveys if conducted during SMC administration or within 2 months afterwards. Such evidence could contribute to broader evaluation of impact of SMC programmes.
Taking stock of global commitments on antimicrobial resistance
Authors: Tejpar Serena , Rogers Van Katwyk Susan , Wilson Lindsay , Hoffman Steven J
Published: May 2022

Over the last six years, antimicrobial resistance (AMR) has generated an unprecedented amount of global attention. This global attention has coincided with an increase in discussion around AMR at various multilateral organisations and international fora. This study catalogues and analyses AMR-related commitments made by the global community following the implementation of the AMR Tripartite’s Global Action Plan (GAP) in 2015. In examining these commitments, we elucidated emergent themes and gaps in AMR discourse through a qualitative content analysis of global political resolutions, declarations and statements made by members of the United Nations, the World Health Assembly, Food and Agriculture Organization Conferences, World Organisation for Animal Health General Sessions, and the G7 and G20 summits and ministerial meetings between the years 2015 and 2021. Emergent themes included AMR research, surveillance and stewardship. Across sectors, fewer commitments were made for specific action on AMR in the environment. The themes and types of commitments were found to be consistent across time and fora but did not evolve into more concrete or nuanced pledges to action between 2015 and 2021. GAP objectives relating to infection prevention and efforts to address the root drivers of AMR appeared the least frequently in our analysis, indicating a lack of global commitment to take a proactive prevention-focused approach to AMR.
Implementing a DHIS2 Ebola virus disease module during the 2021 Guinea Ebola outbreak
Authors: Eggers Carrie , Martel Lise , Dismer Amber , Kallay Ruth , Sayre Dean , Choi Mary , Corvil Salomon , Kaba Almamy , Keita Bakary , Diallo Lamarana , Balde Mamadou Moussa , Bah Mariama , Camara Sekou Mohamed , Koivogui Enogo , Montgomery Joel , Keita Sakoba
Published: May 2022

In 2017, the national agency for health security (L’Agence Nationale de Sécurité Sanitaire—ANSS) in Guinea implemented the District Health Information Software (DHIS2) as the Ministry of Health national surveillance system to capture and report aggregate disease data. During 2019, the ANSS started using DHIS2 Tracker to collect case-based (individual-level) data for epidemic-prone diseases. In 2020, the capability was expanded, and it was used during the COVID-19 pandemic to capture data relevant to the COVID-19 response. When an Ebola virus disease (EVD) outbreak was announced in February 2021, the Tracker module was updated, and enhanced functionalities were developed to meet the needs for the emerging epidemic. This novel EVD module has components to capture information on cases, contacts, alerts, laboratory and vaccinations and provides a centralised site for all EVD outbreak data. It has since been expanded for use with future viral haemorrhagic fever outbreaks.
Effectiveness of adjunctive treatment combined with exercise therapy for patellofemoral pain: a protocol for a systematic review with network meta-analysis of randomised controlled trials
Authors: Souto Larissa Rodrigues , Borges Malu Siqueira , Marcolino Alexandre Marcio , Serrão Fábio Viadanna , Padovez Roberta de Fátima Carreira Moreira
Published: May 2022

Introduction

Patellofemoral pain (PFP) is a chronic condition that affects up to 25% of the general population and has a negative impact on functionality and quality of life due to the high levels of pain experienced by these patients. In order to improve pain and function, rehabilitation programmes that combine adjunctive treatments with exercise therapy are often used in research and clinical settings. However, despite the variety of adjunctive treatments available, their effectiveness when compared with exercise therapy has yet to be elucidated. Thus, the aim of this study is to evaluate the effectiveness of adjunctive treatments plus exercise therapy versus exercise therapy, and determine the relative efficacy of different types of adjunctive treatments plus exercise therapy for individuals with PFP.

Methods and analysis

A systematic review and network meta-analysis will be conducted based on the Cochrane Collaboration recommendations and reported in line with Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We will search Embase, PubMed (MEDLINE), CENTRAL, CINAHL, PEDro, SPORTDiscus, Web of Science and OpenGrey. It will be included randomised controlled trials that compared adjunctive treatment plus exercise therapy to placebo adjunctive treatment plus exercise therapy or exercise therapy. The outcomes of interest will be pain and function, with no restrictions on language, setting or year of publication. Study selection will be performed by two independent reviewers, based on the eligibility criteria. Risk of bias will be assessed using the Physiotherapy Evidence Database scale and the evidence summarised via the Grading of Recommendation, Assessment, Development and Evaluation approach. A Bayesian network meta-analysis will be performed to compare the efficacy of different adjunctive treatments plus exercise therapy. Consistency between direct and indirect comparisons will be assessed.

Ethics and dissemination

No ethical statement will be required for this systematic review and meta-analysis. The findings will be published in a relevant international peer-reviewed journal and presented at conferences.

PROSPERO registration number

CRD42020197081.
Perceptions, views and practices regarding antibiotic prescribing and stewardship among hospital physicians in Jakarta, Indonesia: a questionnaire-based survey
Authors: Limato Ralalicia , Nelwan Erni Juwita , Mudia Manzilina , Alamanda Monik , Manurung Elfrida Rinawaty , Mauleti Ifael Yerosias , Mayasari Maria , Firmansyah Iman , Djaafar Roswin , Vu Huong Thi Lan , van Doorn H Rogier , Broom Alex , Hamers Raph L
Published: May 2022

Objectives

Antibiotic overuse is one of the main drivers of antimicrobial resistance (AMR), especially in low-income and middle-income countries. This study aimed to understand the perceptions and views towards AMR, antibiotic prescribing practice and antimicrobial stewardship (AMS) among hospital physicians in Jakarta, Indonesia.

Design

Cross-sectional, self-administered questionnaire-based survey, with descriptive statistics, exploratory factor analysis (EFA) to identify distinct underlying constructs in the dataset, and multivariable linear regression of factor scores to analyse physician subgroups.

Setting

Six public and private acute-care hospitals in Jakarta in 2019.

Participants

1007 of 1896 (53.1% response rate) antibiotic prescribing physicians.

Results

Physicians acknowledged the significance of AMR and contributing factors, rational antibiotic prescribing, and purpose and usefulness of AMS. However, this conflicted with reported suboptimal local hospital practices, such as room cleaning, hand hygiene and staff education, and views regarding antibiotic decision making. These included insufficiently applying AMS principles and utilising microbiology, lack of confidence in prescribing decisions and defensive prescribing due to pervasive diagnostic uncertainty, fear of patient deterioration or because patients insisted. EFA identified six latent factors (overall Crohnbach’s α=0.85): awareness of AMS activities; awareness of AMS purpose; views regarding rational antibiotic prescribing; confidence in antibiotic prescribing decisions; perception of AMR as a significant problem; and immediate actions to contain AMR. Factor scores differed across hospitals, departments, work experience and medical hierarchy.

Conclusions

AMS implementation in Indonesian hospitals is challenged by institutional, contextual and diagnostic vulnerabilities, resulting in externalising AMR instead of recognising it as a local problem. Appropriate recognition of the contextual determinants of antibiotic prescribing decision making will be critical to change physicians’ attitudes and develop context-specific AMS interventions.
Co-designing an intervention to increase uptake of advance care planning in later life following emergency hospitalisation: a research protocol using accelerated experience-based co-design (AEBCD) and the behaviour change wheel (BCW)
Authors: Bielinska Anna-Maria , Archer Stephanie , Darzi Ara , Urch Catherine
Published: May 2022

Introduction

Despite the potential benefits of advance care planning, uptake in older adults is low. In general, there is a lack of guidance as to how to initiate advance care planning conversations and encourage individuals to take action in planning their future care, including after emergency hospitalisation. Participatory action research methods are harnessed in health services research to design interventions that are relevant to end-users and stakeholders. This study aims to involve older persons, carers and healthcare professionals in co-designing an intervention to increase uptake of advance care planning in later life, which can be used by social contacts and healthcare professionals, particularly in the context of a recent emergency hospitalisation.

Methods and analysis

The theory-driven participatory design research method integrates and adapts accelerated experience-based co-design with the behaviour change wheel, in the form of a collaborative multi-stakeholder co-design workshop. In total, 12 participants, comprising 4 lay persons aged 70+, 4 carers and 4 healthcare professionals with experience in elder care, will be recruited to participate in two online half-day sessions, together comprising one online workshop. There will be a maximum of two workshops. First, in the discovery phase, participants will reflect on findings from earlier qualitative research on views and experiences of advance care planning from three workstreams: patients, carers and healthcare professionals. Second, in the co-design phase, participants will explore practical mechanisms in which older persons aged 70+ can be encouraged to adopt advance care planning behaviours based on the behaviour change wheel, in order to co-design a behavioural intervention to increase uptake of advance care planning in older adults after an emergency hospitalisation.

Ethics and dissemination

Ethical approval has been obtained from the Science Engineering Technology Research Ethics Committee at Imperial College London (Reference: 19IC5538). The findings from this study will be disseminated through publications, conferences and meetings.
Development of dynamic health care delivery heatmaps for end-of-life cancer care: a cohort study
Authors: Khayal Inas S , Brooks Gabriel A , Barnato Amber E
Published: May 2022

Objective

Measures of variation in end-of-life (EOL) care intensity across hospitals are typically summarised using unidimensional measures. These measures do not capture the full dimensionality of complex clinical care trajectories over time that are needed to inform quality improvement efforts. The objective is to develop a novel visual map of EOL care trajectories that illustrates multidimensional utilisation over time.

Setting

United States’ National Cancer Institute or National Comprehensive Cancer Network (NCI/NCCN)-designated hospitals.

Participants

We identified Medicare claims for fee-for-service beneficiaries with poor prognosis cancers who died between April and December 2016 and received the preponderance of treatment in the last 6 months of life at an NCI/NCCN-designated hospital.

Design

For each beneficiary, we transformed each Medicare claim into two elements to generate a two-dimensional individual-level heatmap. On the y-axis, each claim was classified into a categorical description of the service delivered by a healthcare resource. On the x-axis, the date for each claim was converted into the day number prior to death it occurred on. We then summed up individual-level heatmaps of patients attributed to each hospital to generate two-dimensional hospital-level heatmaps. We used four case studies to illustrate the feasibility of interpreting these heatmaps and to shed light on how they might be used to guide value-based, quality improvement initiatives.

Results

We identified nine distinct EOL care delivery patterns from hospital-level heatmaps based on signal intensity and patterns for inpatient, outpatient and home-based hospice services. We illustrate that in most cases, heatmaps illustrating patterns of multidimensional healthcare utilisation over time provide more information about care trajectories and highlight more heterogeneity than current unidimensional measures.

Conclusions

This study illustrates the feasibility of representing multidimensional EOL utilisation over time as a heatmap. These heatmaps may provide potentially actionable insights into hospital-level care delivery patterns, and the approach may generalise to other serious illness populations.
Association of different kinds of obesity with diabetic retinopathy in patients with type 2 diabetes
Authors: Li Wangting , Gong Xia , Wang Wei , Xiong Kun , Meng Jie , Li Yuting , Wang Lanhua , Liang Xiaoling , Jin Ling , Huang Wenyong
Published: May 2022

Introduction

Although obesity is one of the established risk factors of diabetes mellitus, the relationship between obesity and diabetic retinopathy (DR) remains unclear in different studies. This study aimed to investigate the association of DR with four obesity-related indexes, including body mass index (BMI), waist to hip ratio (WHR), waist to height ratio (WHtR) and body adiposity index (BAI) in patients with diabetes.

Research design and methods

We prospectively enrolled 2305 patients with diabetes (2305 eyes) in the Guangzhou Diabetic Eye Study between November 2017 and December 2019 to investigate the prevalence and the association of different types of obesity with DR using BMI, WHR, WHtR and BAI. DR, diabetic macular oedema (DME) and vision-threatening DR (VTDR) were selected as primary outcomes. BMI was categorised as normal (18.5–22.9 kg/m2), overweight (23.0–25.0 kg/m2) and obese (>25.0 kg/m2); WHR, WHtR and BAI were categorised into quarters.

Results

A total of 336 (14.58%), 93 (4.03%) and 98 (4.25%) developed DR, DME and VTDR, respectively. The prevalence of DR, DME and VTDR was higher in patients with higher BMI/WHR or lower WHtR/BAI. In the univariate regression model, WHR correlated positively with DR, while WHtR and BAI correlated negatively with DR, DME and VTDR. The association remained independent of age, sex and lipid metabolism parameters. In the multivariate model, obese presented as a protective factor for DME and VTDR, while the second quarter of WHtR(Q2-WHtR) presented as a risk factor.

Conclusions

As high as 67.8% of patients with diabetes were overweight or obese. Obese presented as a significant protective factor of VTDR, while Q2-WHtR presented as a significant risk factor. Therefore, more attention should be paid to centripetal obesity as well as general obesity. Further research is also needed to focus on the improvement of sex-specific weight management in patients with diabetes.
Qualitative study exploring the experiences and perceptions of dolutegravir/lamivudine dual antiretroviral therapy (the PEDAL study) in people living with HIV: protocol
Authors: Villa Giovanni , Garcia Rodriguez Diego , Fray David , Clarke Amanda , Ackley Caroline
Published: May 2022

Introduction

Antiretroviral treatment turned HIV infection into a chronic disease and improved quality of life for people living with HIV. Dual-drug combinations have been shown to be effective in suppressing viral replication and can potentially reduce long-term drug-associated toxicities. We aim to investigate patients’ perceptions and experiences on the safety, effectiveness, tolerability and unmet needs of the dual-drug combination dolutegravir/lamivudine in Brighton and Hove, UK. In addition, we will conduct a comparative analysis between patients on dolutegravir/lamivudine and patients on other dual-drug and three-drug combinations. Finally, the study aims to provide recommendations to improve doctor–patient communication, knowledge and understanding of the treatment plan, and additional care that ought to be considered in patient-centred, holistic care plans.

Methods and analysis

Our qualitative methodological framework is based on three main methods: cultural domain analysis, focus group discussions and in-depth interviews. Cultural domain analysis employs a range of techniques (free listing, pile sorts and rankings) to elicit terms from informants regarding specific cultural domains (ie, groups of items that are perceived to be of the same kind). This framework has been codesigned with a patient representative to ensure relevance, suitability and coproduction of knowledge. All methods have been tested to take place online, as an option, via Zoom, Skype or Microsoft Teams. Padlet, an application to create online boards, will be used during the cultural domain analysis session. Data collected will be analysed following the completion of each method embracing an iterative approach through applied thematic analysis.

Ethics and dissemination

Ethical approval was obtained from the Health Research Authority (Reference 21/NW/0070). Findings will be used to produce recommendations to improve doctor and patient communication by identifying patients’ fears, worries, misconceptions and general concerns of their drug regimen. Conclusions will be disseminated via journal articles, conference papers and discussions through public engagement events.

Project registration number

IRAS number: 286277.NCT04901728.
Linkage of National Congenital Heart Disease Audit data to hospital, critical care and mortality national data sets to enable research focused on quality improvement
Authors: Espuny Pujol Ferran , Pagel Christina , Brown Katherine L , Doidge James C , Feltbower Richard G , Franklin Rodney C , Gonzalez-Izquierdo Arturo , Gould Doug W , Norman Lee J , Stickley John , Taylor Julie A , Crowe Sonya
Published: May 2022

Objectives

To link five national data sets (three registries, two administrative) and create longitudinal healthcare trajectories for patients with congenital heart disease (CHD), describing the quality and the summary statistics of the linked data set.

Design

Bespoke linkage of record-level patient identifiers across five national data sets. Generation of spells of care defined as periods of time-overlapping events across the data sets.

Setting

National Congenital Heart Disease Audit (NCHDA) procedures in public (National Health Service; NHS) hospitals in England and Wales, paediatric and adult intensive care data sets (Paediatric Intensive Care Audit Network; PICANet and the Case Mix Programme from the Intensive Care National Audit & Research Centre; ICNARC-CMP), administrative hospital episodes (hospital episode statistics; HES inpatient, outpatient, accident and emergency; A&E) and mortality registry data.

Participants

Patients with any CHD procedure recorded in NCHDA between April 2000 and March 2017 from public hospitals.

Primary and secondary outcome measures

Primary: number of linked records, number of unique patients and number of generated spells of care. Secondary: quality and completeness of linkage.

Results

There were 143 862 records in NCHDA relating to 96 041 unique patients. We identified 65 797 linked PICANet patient admissions, 4664 linked ICNARC-CMP admissions and over 6 million linked HES episodes of care (1.1M inpatient, 4.7M outpatient). The linked data set had 4 908 153 spells of care after quality checks, with a median (IQR) of 3.4 (1.8–6.3) spells per patient-year. Where linkage was feasible (in terms of year and centre), 95.6% surgical procedure records were linked to a corresponding HES record, 93.9% paediatric (cardiac) surgery procedure records to a corresponding PICANet admission and 76.8% adult surgery procedure records to a corresponding ICNARC-CMP record.

Conclusions

We successfully linked four national data sets to the core data set of all CHD procedures performed between 2000 and 2017. This will enable a much richer analysis of longitudinal patient journeys and outcomes. We hope that our detailed description of the linkage process will be useful to others looking to link national data sets to address important research priorities.
Improving patient and clinician safety during COVID-19 through rapidly adaptive simulation and a randomised controlled trial: a study protocol
Authors: Evans Leigh V , Ray Jessica M , Bonz James W , Joseph Melissa , Gerwin Jeffrey N , Dziura James D , Venkatesh Arjun K , Wong Ambrose H
Published: May 2022

Introduction

COVID-19 required healthcare systems to iteratively adapt for safe and up-to-date care as knowledge of the disease rapidly evolved. Rates of COVID-19 infections continue to fluctuate and patients without COVID-19 increasingly return to the emergency department (ED) for care. This leads to new challenges and threats to patient and clinician safety as suspected patients with COVID-19 need to be quickly detected and isolated among other patients with non-COVID-19-related illnesses. At the front lines, emergency physicians also face continued personal safety concerns and increased work burden, which heighten stress and anxiety, especially given the prolonged course of the pandemic. Burnout, already a serious concern for emergency physicians due to the cumulative stresses of their daily practice, may present as a longer-term outcome of these acute stressors.

Methods and analysis

We will implement a rapidly adaptive simulation-based approach to understand and improve physician preparedness while decreasing physician stress and anxiety. First, we will conduct semi-structured qualitative interviews and human factor observations to determine the challenges and facilitators of COVID-19 preparedness and mitigation of physician stress. Next, we will conduct a randomised controlled trial to test the effectiveness of a simulation preparedness intervention on physician physiological stress as measured by decreased heart rate variability on shift and anxiety as measured by the State-Trait Anxiety Inventory.

Ethics and dissemination

The protocol was reviewed and approved by the Agency for Healthcare Research and Quality for funding, and ethics approval was obtained from the Yale University Human Investigation Committee in 2020 (HIC# 2000029370 and 2000029372). To support ongoing efforts to address clinician stress and preparedness, we will strategically disseminate the simulation intervention to areas most impacted by COVID-19. Using a virtual telesimulation and webinar format, the dissemination efforts will provide hands-on learning for ED and hospital administrators as well as simulation educators.

Trial registration number

NCT04614844.
Cystic fibrosis learning network telehealth innovation lab during the COVID-19 pandemic: a success QI story for interdisciplinary care and agenda setting
Authors: Albon Dana , Thomas Lacrecia , Hoberg Lindsay , Stamper Sophia , Somerville Lindsay , Varghese Prigi , Balasa Ella , Roman Matthew , Britto Maria T , Miner Melanie , Gehring Emily , Gammon Clifford , Amin Raouf S , Seid Michael , Powers Mike
Published: May 2022

Introduction

The Cystic Fibrosis Foundation chronic care guidelines recommend monitoring clinical status of a patient with cystic fibrosis (CF) through quarterly interdisciplinary visits. At the beginning of the COVID-19 pandemic, the Cystic Fibrosis Learning Network (CFLN) designed and initiated a telehealth (TH) innovation lab (TH ILab) to support transition from the classic CF care model of quarterly in-person office visits to a care model that included TH.

Aim

The specific aims of the TH ILab were to increase the percentage of virtual visits with interdisciplinary care (IDC) from 60% to 85% and increase the percentage of virtual visits in which patients and families participated in shared agenda setting (AS) from 52% to 85% by 31 December 2020.

Methods

The model for improvement methodology was used to determine the ILab aims, theory, interventions and measures. In the testing phase of the ILab, data related to process and outcome measures as well as learnings from plan–do–study–act cycles were collected, analysed and shared weekly with the TH ILab teams. Participating centres created processes for IDC and AS for TH visits and developed and shared quality improvement tools specific to their local context with other centres during the ILab weekly meetings and via a secure CFLN-maintained platform.

Results

Both specific aims were achieved ahead of the expected target date. By August 2020, 85% of the TH ILab visits provided IDC and 92% of patients were seen for CF care by teams from the TH ILab that participated in AS.

Conclusion

Shared learning through a collaborative, data-driven process in the CFLN TH ILab rapidly led to standardised TH IDC and AS, which achieved reliable and sustainable processes which could be reproduced by other networks.