bluuebunny/crossref_metadata_2025 huggingface dataset:
Objective Measures of Physical Activity in Rural Communities: Factors Associated With a Valid Wear and Lessons Learned
Authors: Gilbert Amanda , Beck Alan , Serrano Natalicio , Brownson Ross C.
Published: March 2022

Background: Compared with urban/suburban counterparts, rural communities experience lower rates of physical activity (PA) and higher rates of chronic disease. Promoting PA is important for disease prevention but requires reliable and valid measurement of PA. However, little is known about effectively collecting objective PA data in rural communities. Using data from a cluster randomized trial (Heartland Moves), which aims to increase PA in rural Missouri, this study explored factors associated with successful objective PA data collection and presents lessons learned. Methods: Baseline survey and accelerometry data were collected through Heartland Moves (n = 368) from August 2019 to February 2021, in southeast Missouri. Chi-square and logistic regression analyses were used to explore factors (demographics, subjective PA, and SMS reminders) associated with valid wear of PA devices. Results: Overall, 77% had valid wears. Participants who were not married (odds ratio [OR] 0.48, 95% confidence interval [CI], 0.30–0.79) and those living alone (OR 0.49, 95% CI, 0.30–0.81) were less likely to have valid wears. Participants who met PA guidelines (OR 1.69, 95% CI, 1.03–2.75) or received SMS reminders (OR 3.25; 95% CI, 1.97–5.38) were more likely to have valid wears. Conclusions: Results are supported by lessons learned, including importance of communication (SMS reminders), accessing hard-to-reach groups (living alone), and need to adapt during data collection.
Visualization of on-surface ethylene polymerization through ethylene insertion
Authors: Guo Weijun , Yin Junqing , Xu Zhen , Li Wentao , Peng Zhantao , Weststrate C. J. , Yu Xin , He Yurong , Cao Zhi , Wen Xiaodong , Yang Yong , Wu Kai , Li Yongwang , Niemantsverdriet J. W. , Zhou Xiong
Published: March 2022

Polyethylene production through catalytic ethylene polymerization is one of the most common processes in the chemical industry. The popular Cossee-Arlman mechanism hypothesizes that the ethylene be directly inserted into the metal–carbon bond during chain growth, which has been awaiting microscopic and spatiotemporal experimental confirmation. Here, we report an in situ visualization of ethylene polymerization by scanning tunneling microscopy on a carburized iron single-crystal surface. We observed that ethylene polymerization proceeds on a specific triangular iron site at the boundary between two carbide domains. Without an activator, an intermediate, attributed to surface-anchored ethylidene (CHCH
3
), serves as the chain initiator (self-initiation), which subsequently grows by ethylene insertion. Our finding provides direct experimental evidence of the ethylene polymerization pathway at the molecular level.
Angiotensin-converting enzyme gates brain circuit–specific plasticity via an endogenous opioid
Authors: Trieu Brian H. , Remmers Bailey C. , Toddes Carlee , Brandner Dieter D. , Lefevre Emilia M. , Kocharian Adrina , Retzlaff Cassandra L. , Dick Rachel M. , Mashal Mohammed A. , Gauthier Elysia A. , Xie Wei , Zhang Ying , More Swati S. , Rothwell Patrick E.
Published: March 2022

Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is especially abundant in striatal tissue, but the function of ACE in striatal circuits remains poorly understood. We found that ACE degrades an unconventional enkephalin heptapeptide, Met-enkephalin-Arg-Phe, in the nucleus accumbens of mice. ACE inhibition enhanced µ-opioid receptor activation by Met-enkephalin-Arg-Phe, causing a cell type–specific long-term depression of glutamate release onto medium spiny projection neurons expressing the Drd1 dopamine receptor. Systemic ACE inhibition was not intrinsically rewarding, but it led to a decrease in conditioned place preference caused by fentanyl administration and an enhancement of reciprocal social interaction. Our results raise the enticing prospect that central ACE inhibition can boost endogenous opioid signaling for clinical benefit while mitigating the risk of addiction.
Frequency multiplication by collective nanoscale spin-wave dynamics
Authors: Koerner Chris , Dreyer Rouven , Wagener Martin , Liebing Niklas , Bauer Hans G. , Woltersdorf Georg
Published: March 2022

Frequency multiplication is a process in modern electronics in which harmonics of the input frequency are generated in nonlinear electronic circuits. Devices based on the propagation and interaction of spin waves are a promising alternative to conventional electronics. The characteristic frequency of these excitations is in the gigahertz (GHz) range and devices are not readily interfaced with conventional electronics. Here, we locally probe the magnetic excitations in a soft magnetic material by optical methods and show that megahertz-range excitation frequencies cause switching effects on the micrometer scale, leading to phase-locked spin-wave emission in the GHz range. Indeed, the frequency multiplication process inside the magnetic medium covers six octaves and opens exciting perspectives for spintronic applications, such as all-magnetic mixers or on-chip GHz sources.
The immunology and immunopathology of COVID-19
Authors: Merad Miriam , Blish Catherine A. , Sallusto Federica , Iwasaki Akiko
Published: March 2022

Considerable research effort has been made worldwide to decipher the immune response triggered upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, identify the drivers of severe and fatal COVID-19, and understand what leads to the prolongation of symptoms after disease resolution. We review the results of almost 2 years of COVID-19 immunology research and discuss definitive findings and remaining questions regarding our understanding of COVID-19 pathophysiology. We discuss emerging understanding of differences in immune responses seen in those with and without Long Covid syndrome, also known as post-acute sequelae of SARS-CoV-2. We hope that the knowledge gained from this COVID-19 research will be applied in studies of inflammatory processes involved in critical and chronic illnesses, which remain a major unmet need.
Structural basis of human telomerase recruitment by TPP1-POT1
Authors: Sekne Zala , Ghanim George E. , van Roon Anne-Marie M. , Nguyen Thi Hoang Duong
Published: March 2022

Telomerase maintains genome stability by extending the 3′ telomeric repeats at eukaryotic chromosome ends, thereby counterbalancing progressive loss caused by incomplete genome replication. In mammals, telomerase recruitment to telomeres is mediated by TPP1, which assembles as a heterodimer with POT1. We report structures of DNA-bound telomerase in complex with TPP1 and with TPP1-POT1 at 3.2- and 3.9-angstrom resolution, respectively. Our structures define interactions between telomerase and TPP1-POT1 that are crucial for telomerase recruitment to telomeres. The presence of TPP1-POT1 stabilizes the DNA, revealing an unexpected path by which DNA exits the telomerase active site and a DNA anchor site on telomerase that is important for telomerase processivity. Our findings rationalize extensive prior genetic and biochemical findings and provide a framework for future mechanistic work on telomerase regulation.
Sanctifying work in Silicon Valley
Work Pray Code: When Work Becomes Religion in Silicon Valley
Carolyn Chen
Princeton University Press, 2022. 272 pp.
Authors: English-Lueck J. A.
Published: March 2022

What is lost when spiritual practices are secularized for the workplace?
Structure of a Janus kinase cytokine receptor complex reveals the basis for dimeric activation
Authors: Glassman Caleb R. , Tsutsumi Naotaka , Saxton Robert A. , Lupardus Patrick J. , Jude Kevin M. , Garcia K. Christopher
Published: March 2022

Cytokines signal through cell surface receptor dimers to initiate activation of intracellular Janus kinases (JAKs). We report the 3.6-angstrom–resolution cryo–electron microscopy structure of full-length JAK1 complexed with a cytokine receptor intracellular domain Box1 and Box2 regions captured as an activated homodimer bearing the valine→phenylalanine (VF) mutation prevalent in myeloproliferative neoplasms. The seven domains of JAK1 form an extended structural unit, the dimerization of which is mediated by close-packing of the pseudokinase (PK) domains from the monomeric subunits. The oncogenic VF mutation lies within the core of the JAK1 PK interdimer interface, enhancing packing complementarity to facilitate ligand-independent activation. The carboxy-terminal tyrosine kinase domains are poised for transactivation and to phosphorylate the receptor STAT (signal transducer and activator of transcription)–recruiting motifs projecting from the overhanging FERM (four-point-one, ezrin, radixin, moesin)–SH2 (Src homology 2)-domains. Mapping of constitutively active JAK mutants supports a two-step allosteric activation mechanism and reveals opportunities for selective therapeutic targeting of oncogenic JAK signaling.
Growing polymers, caught in the act
Authors: Wintterlin Joost
Published: March 2022

Researchers show the polymerization of ethylene at the active centers of a catalyst
In Other Journals
Authors: Vignieri Sacha , Hurtley Stella M. , Ash Caroline , Stern Peter , Grocholski Brent , Osborne Ian S. , Smith H. Jesse
Published: March 2022

Editors’ selections from the current scientific literature
When is a pandemic officially ‘over’?
Authors: Wadman Meredith
Published: March 2022

World Health Organization will confront thorny decision with big implications
Targeted Amplicon Deep Sequencing for Monitoring Antimalarial Resistance Markers in Western Kenya
Authors: Osoti Victor , Akinyi Mercy , Wamae Kevin , Kimenyi Kelvin M. , de Laurent Zaydah , Ndwiga Leonard , Gichuki Paul , Okoyo Collins , Kepha Stella , Mwandawiro Charles , Kandie Regina , Bejon Philip , Snow Robert W. , Ochola-Oyier Lynette Isabella
Published: March 2022

Molecular surveillance of
Plasmodium falciparum
parasites is important to track emerging and new mutations and trends in established mutations and should serve as an early warning system for antimalarial resistance. Dried blood spots were obtained from a
Plasmodium falciparum
malaria survey in school children conducted across eight counties in western Kenya in 2019.
RACK1 Associates with RNA-Binding Proteins Vigilin and SERBP1 to Facilitate Dengue Virus Replication
Authors: Brugier Alexis , Hafirrassou Mohamed Lamine , Pourcelot Marie , Baldaccini Morgane , Kril Vasiliya , Couture Laurine , Kümmerer Beate M. , Gallois-Montbrun Sarah , Bonnet-Madin Lucie , Vidalain Pierre-Olivier , Delaugerre Constance , Pfeffer Sébastien , Meertens Laurent , Amara Ali
Published: March 2022

We recently identified the scaffolding RACK1 protein as an important host-dependency factor for dengue virus (DENV), a positive-stranded RNA virus responsible for the most prevalent mosquito-borne viral disease worldwide. Here, we have performed the first RACK1 interactome in human cells and identified Vigilin and SERBP1 as DENV host-dependency factors.
Structural and Biochemical Basis for Development of Diketo Acid Inhibitors Targeting the Cap-Snatching Endonuclease of the Ebinur Lake Virus (Order:
Bunyavirales
)
Authors: Kuang Wenhua , Zhang Huanyu , Cai Yan , Zhang Guilin , Deng Fei , Li Hailong , Zhou Yiwu , Wang Manli , Gong Peng , Guo Yu , Hu Zhihong
Published: March 2022

The
Bunyavirales
contain many important human pathogens such as Crimean-Congo hemorrhagic fever virus and Lassa virus that pose serious threats to public health; however, currently there are no specific antiviral drugs against these viruses. The diketo acid inhibitor L-742,001 is a potential drug as it inactivates the cap-snatching endonuclease (EN) encoded by bunyaviruses.
Supplemental Material: Stratigraphy of the Eocene–Oligocene Titus Canyon Formation, Death Valley, California, and Eocene extensional tectonism in the Basin and Range
Authors: Midttun N. , al. et
Published: March 2022

Files removed. Please see Notice of Withdrawal at https://doi.org/10.1130/GES02363.1.
Effect of resistance training on HbA1c in adults with type 2 diabetes mellitus and the moderating effect of changes in muscular strength: a systematic review and meta-analysis
Authors: Jansson Anna K , Chan Li X , Lubans David R , Duncan Mitch J , Plotnikoff Ronald C
Published: March 2022

Type 2 diabetes mellitus (T2DM) accounts for approximately 90% of diabetes cases globally. Regular physical activity is regarded as one of the key components in T2DM management. Aerobic exercise was traditionally recommended; however, there is a growing body of research examining the independent effect of resistance training (RT) on glycemic control. This systematic review and meta-analysis aimed to conduct an update on the effects of RT on glycosylated hemoglobin (HbA1c) in adults with T2DM and examine the moderating effects of training effect (ie, muscular strength improvements), risk of bias and intervention duration. Peer-reviewed articles published in English were searched across MEDLINE, Embase, CINAHL, Scopus and SPORTDiscus from database inception until January 19, 2021. Each online database was systematically searched for randomized controlled trials reporting on the effects of RT on HbA1c in individuals with T2DM. Twenty studies (n=1172) were included in the meta-analysis. RT significantly reduced HbA1c compared with controls (weighted mean difference=−0.39, 95% CI −0.60 to −0.18, p<0.001, I2=69.20). Training effect significantly (p<0.05) moderated the results, with larger improvements in muscular strength leading to greater reductions in HbA1c (β=−0.99, CI −1.97 to −0.01). Intervention duration and risk of bias did not significantly moderate the effects. As a secondary analysis, this study found no significant differences in HbA1c when comparing RT and aerobic training (p=0.42). This study demonstrates that RT is an effective strategy to decrease HbA1c in individuals with T2DM. Importantly, RT interventions that had a larger training effect appeared more effective in reducing HbA1c, compared with interventions producing medium and small effects.

PROSPERO registration numberCRD42020134046.
Factors determining development of researchers within a research network on cancer diagnosis in primary care (CanTest): an interview study
Authors: de Groot Esther , Vermond Debbie , Sills Valerie A , Mol Saskia S L , Walter Fiona M , Rubin Greg , de Wit Niek J
Published: March 2022

Objectives

Developing connections with other researchers in a network, learning informally through these connections and using them to reach goals, is expected to increase research capacity and strengthen performance. So far, this has not been empirically demonstrated. We assessed what and how network collaboration adds to development of researchers.

Design

Exploratory qualitative study using semistructured online interviews, analysed by inductive and deductive methods. For the deductive analysis, an existing value creation framework to study informal learning in networks was used and adjusted to our context.

Setting

The CanTest Collaborative—an international team of primary care cancer researchers working on early detection and diagnosis of cancer.

Participants

Sixteen primary care cancer researchers.

Results

Connections with other researchers in an international network created diverse value cycles, where most outcomes were in the potential value cycle, acquiring knowledge, skills, social capital, resources and ideas. Not all potential value will be applied but many interviewees described realised as well as transformational value. In our context, the transformational value from the framework appeared to be related to other perspectives on the research process. Advancement of the network depends on opportunities, timing, role models and connections between different perspectives.

Conclusions

Focus on the factors that are relevant for network advancement will support researchers in early detection and diagnosis of cancer research patients who participate in an international network and bring sustainable change in this domain. When, subsequently, researchers in the CanTest network bring about more realised and transformational learning outcomes, this will contribute to capacity development.
Individual-level and community-level factors associated with eight or more antenatal care contacts in sub-Saharan Africa: evidence from 36 sub-Saharan African countries
Authors: Tessema Zemenu Tadesse , Tesema Getayeneh Antehunegn , Yazachew Lake
Published: March 2022

Objective

To reduce maternal mortality, the WHO has been introducing several antenatal care (ANC) measures. Pregnancy-related preventable morbidity and mortality, on the other hand, remain alarmingly high. This study was conducted to estimate the magnitude and the factors associated with eight or more ANC visits in sub-Saharan Africa.

Design

A population-based, cross-sectional investigation was conducted.

Setting

Sub-Saharan African countries.

Participants

A total of 300 575 women from recent Demographic and Health Surveys (DHS) conducted in 36 sub-Saharan African countries from 2006 to 2018 were included in this study.

Methods

The data were sourced from sub-Saharan African countries’ recent DHS data set from 2006 to 2018. A multilevel logistic regression model was fitted to identify factors associated with ANC use. Adjusted OR, with 95% CI and a p value of less than 0.05, was employed to determine parameters linked to ANC use.

Results

The pooled magnitude of eight or more ANC visits in sub-Saharan African countries was 6.8% (95% CI 6.7% to 6.9%). Residence, maternal education, husband’s education, maternal occupation, wealth index, media exposure, contraceptive use and desired pregnancy were all positively associated with eight or more ANC visits in the multilevel logistic regression analysis, whereas birth order was negatively associated with eight or more ANC visits.

Conclusions

Compliance with the WHO guidelines on the minimum number of ANC contacts in sub-Saharan Africa is poor. We recommend that mother and child health programmes review existing policies and develop new policies to adopt, execute and address the obstacles to maintaining the WHO-recommended minimum of eight ANC interactions. Women’s education, economic position, media exposure and family planning uptake should be prioritised and improved. Urgent intervention is required to meet the minimum of eight ANC contacts in sub-Saharan Africa.
Risk of pneumonia in asthmatic children using inhaled corticosteroids: a nested case-control study in a birth cohort
Authors: Shrestha Pragya , Wi Chung-Il , Liu Hongfang , King Katherine S , Ryu Euijung , Kwon Jung Hyun , Sohn Sunghwan , Park Miguel , Juhn Young
Published: March 2022

Background

Inhaled corticosteroids (ICSs) are important in asthma management, but there are concerns regarding associated risk of pneumonia. While studies in asthmatic adults have shown inconsistent results, this risk in asthmatic children is unclear.

Objective

Our aim was to determine the association of ICS use with pneumonia risk in asthmatic children.

Methods

A nested case-control study was performed in the Mayo Clinic Birth Cohort. Asthmatic children (<18 years) with a physician diagnosis of asthma were identified from electronic medical records of children born at Mayo Clinic from 1997 to 2016 and followed until 31 December 2017. Pneumonia cases defined by Infectious Disease Society of America were 1:1 matched with controls without pneumonia by age, sex and asthma index date. Exposure was defined as ICS prescription at least 90 days prior to pneumonia. Associations of ICS use, type and dose (low, medium and high) with pneumonia risk were analysed using conditional logistic regression.

Results

Of the 2108 asthmatic children eligible for the study (70% mild intermittent and 30% persistent asthma), 312 children developed pneumonia during the study period. ICS use overall was not associated with risk of pneumonia (adjusted OR: 0.94, 95% CI: 0.62 to 1.41). Poorly controlled asthma was significantly associated with the risk of pneumonia (OR: 2.03, 95% CI: 1.35 to 3.05; p<0.001). No ICS type or dose was associated with risk of pneumonia.

Conclusion

ICS use in asthmatic children was not associated with risk of pneumonia but poorly controlled asthma was. Future asthma studies may need to include pneumonia as a potential outcome of asthma management.
Enhancing higher education student well-being through social prescribing: a realist evaluation protocol
Authors: Wallace Sarah , Wallace Carolyn , Elliott Megan , Davies Mark , Pontin David
Published: March 2022

Introduction

UK higher education (HE) student numbers are increasing and students report higher levels of mental health and well-being issues. Social prescribing links individuals to community-based, non-medical support. It is widely implemented throughout the UK, and is supported by the Welsh Government. This protocol presents an evaluation of a new social prescribing service to enhance student well-being, a first for UK HE students.

Methods and analysis

A realist evaluation to articulate why, how and to what extent and circumstances social prescribing works for students, using a mixed-methods sequential design of four cycles. Cycle 1 informs the model and programme theory development of how the model works; activities include a Realist Review, Group Concept Mapping and producing bilingual short films about the evaluation and model. Cycle 2 involves secondary analysis of routine service data, and outcome measurements from students receiving a social prescription. Cycle 3 uses reflective diaries and qualitative realist interviews with stakeholders to understand the process and outcome of the model. Cycle 4 concludes with a world café workshop with stakeholders to agree and finalise the framework specification of ‘how, why, when and to what extent’ the model works. A meta-matrix construction will determine convergence, complementarity or discrepancy across the cycles. An advisory group of key stakeholders informs each cycle.

Ethics and dissemination

University of South Wales Life Sciences and Education Ethics Committee and Wrexham Glyndwr University (WGU) Research Ethics Sub-Committee approved secondary data analysis of participant demographics (200 805LRL:USW, id441:WGU), outcome measurement tools (200 902LR:USW, id441:WGU) and qualitative data collection (200 804LR:USW, id449:WGU). The authors will publish findings in peer-reviewed journals, produce an evaluation report to the funder and a short film for dissemination via stakeholders, university networks, United Nations Regional Centre of Expertise in Wales, PRIME Centre Wales, Wales School for Social Prescribing Research, conferences and social media.
Defining decision thresholds for judgments on health benefits and harms using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Evidence to Decision (EtD) frameworks: a protocol for a randomised methodological study (GRADE-THRESHOLD)
Authors: Morgano Gian Paolo , Mbuagbaw Lawrence , Santesso Nancy , Xie Feng , Brozek Jan L , Siebert Uwe , Bognanni Antonio , Wiercioch Wojtek , Piggott Thomas , Darzi Andrea J , Akl Elie A , Verstijnen Ilse M , Parmelli Elena , Saz-Parkinson Zuleika , Alonso-Coello Pablo , Schünemann Holger J
Published: March 2022

Introduction

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) and similar Evidence to Decision (EtD) frameworks require its users to judge how substantial the effects of interventions are on desirable and undesirable people-important health outcomes. However, decision thresholds (DTs) that could help understand the magnitude of intervention effects and serve as reference for interpretation of findings are not yet available.

The objective of this study is an approach to derive and use DTs for EtD judgments about the magnitude of health benefits and harms. We hypothesise that approximate DTs could have the ability to discriminate between the existing four categories of EtD judgments (Trivial, Small, Moderate, Large), support panels of decision-makers in their work, and promote consistency and transparency in judgments.

Methods and analysis

We will conduct a methodological randomised controlled trial to collect the data that allow deriving the DTs. We will invite clinicians, epidemiologists, decision scientists, health research methodologists, experts in Health Technology Assessment (HTA), members of guideline development groups and the public to participate in the trial. Then, we will investigate the validity of our DTs by measuring the agreement between judgments that were made in the past by guideline panels and the judgments that our DTs approach would suggest if applied on the same guideline data.

Ethics and dissemination

The Hamilton Integrated Research Ethics Board reviewed this study as a quality improvement study and determined that it requires no further consent. Survey participants will be required to read a consent statement in order to participate in this study at the beginning of the trial. This statement reads: You are being invited to participate in a research project which aims to identify indicative DTs that could assist users of the GRADE EtD frameworks in making judgments. Your input will be used in determining these indicative thresholds. By completing this survey, you provide consent that the anonymised data collected will be used for the research study and to be summarised in aggregate in publication and electronic tools.

PROTOCOL registration number

NCT05237635.
Burden of whooping cough in China (PertussisChina): study protocol of a prospective, population-based case–control study
Authors: Yu Jianxing , He Hanqing , Zhang Yanyang , Gao Yuan , Chen Chuanwei , Xu Juan , Xu Li , Zhang Xiaoxiao , Zhou Qianqian , Zhu Yao , Tang Xuewen , Guo Yonghao , Chen Zhiping , Shao Zhujun
Published: March 2022

Introduction

Pertussis is one of the top 10 diseases of children under 10 years of age, and the few vaccine-preventable diseases who is on a rise in China in recent years; however, the true burden of pertussis, including age-stratified incidence and risk factors of severe sequelae, are under-recognised. We aim to estimate the health burden of laboratory-confirmed pertussis by age groups, considering the setting of illness onset (ie, in community, outpatient and inpatient), in a Chinese population (~2.23 million in total) at two sites.

Methods and analysis

This paper describes the study design of a 1-year, prospective, age-stratified and population-based case–control study, including site selection, study population, case registry, ascertainment and enrolment, control recruitment, follow-up of case, microbiological methods, data collection, quality control activities and statistical methods used to generate incidence estimates. During June 2021 through May 2022, registry of suspected pertussis cases (namely chronic/persistent cough) will be conducted in several participating hospitals (SHs) at the two sites, which are selected based on Healthcare Utilisation and Attitudes Surveys (HUAS) carried out before study initiation. A case–control study will be conducted in the SHs and we aim to enrol a total of 1000 suspected pertussis cases (ie, all hospital admissions and the first 1–3 outpatient visits each week each hospital) and 2000 frequency matched healthy controls in community. Our primary study outcome, the laboratory-confirmed Bordetella pertussis infection, will be determined by a comprehensive laboratory methods and procedures (ie, culture, PCR and serological tests) in both cases and controls at enrolment and during 60-day’s follow-up visits. Finally, data from HUAS (ie, population size), case registry (ie, the total number of suspected pertussis cases) and case–control study (ie, the prevalence or population attributable fraction of Bordetella pertussis) will be combined to calculate incidence and its 95% CI through bootstrap method. Epidemiological analyses will be conducted to determine the risk factors associated with severe sequelae of pertussis.

Ethics and dissemination

This study has been approved by Chinese Centre for Disease Control and Prevention’s Institutional Review Board (no. ICDC-202110). Results will be disseminated via academic presentations and publication in peer-reviewed journals, and will provide valuable scientific data and some new insights into the incidence, aetiology and risk factors for severe sequelae of pertussis to academic societies and the public health authorities who is currently struggling and fighting against this burdensome disease worldwide.
Safety and pharmacokinetics-pharmacodynamics of a shorter tuberculosis treatment with high-dose pyrazinamide and rifampicin: a study protocol of a phase II clinical trial (HighShort-RP)
Authors: Ekqvist David , Bornefall Anna , Augustinsson Daniel , Sönnerbrandt Martina , Nordvall Michaela Jonsson , Fredrikson Mats , Carlsson Björn , Sandstedt Mårten , Simonsson Ulrika S H , Alffenaar Jan-Willem C , Paues Jakob , Niward Katarina
Published: March 2022

Introduction

Increased dosing of rifampicin and pyrazinamide seems a viable strategy to shorten treatment and prevent relapse of drug-susceptible tuberculosis (TB), but safety and efficacy remains to be confirmed. This clinical trial aims to explore safety and pharmacokinetics-pharmacodynamics of a high-dose pyrazinamide-rifampicin regimen.

Methods and analysis

Adult patients with pulmonary TB admitted to six hospitals in Sweden and subjected to receive first-line treatment are included. Patients are randomised (1:3) to either 6-month standardised TB treatment or a 4-month regimen based on high-dose pyrazinamide (40 mg/kg) and rifampicin (35 mg/kg) along with standard doses of isoniazid and ethambutol. Plasma samples for measurement of drug exposure determined by liquid chromatography tandem-mass spectrometry are obtained at 0, 1, 2, 4, 6, 8, 12 and 24 hours, at day 1 and 14. Maximal drug concentration (Cmax) and area under the concentration-time curve (AUC0-24h) are estimated by non-compartmental analysis. Conditions for early model-informed precision dosing of high-dose pyrazinamide-rifampicin are pharmacometrically explored. Adverse drug effects are monitored throughout the study and graded according to Common Terminology Criteria for Adverse Events V.5.0. Early bactericidal activity is assessed by time to positivity in BACTEC MGIT 960 of induced sputum collected at day 0, 5, 8, 15 and week 8. Minimum inhibitory concentrations of first-line drugs are determined using broth microdilution. Disease severity is assessed with X-ray grading and a validated clinical scoring tool (TBscore II). Clinical outcome is registered according to WHO definitions (2020) in addition to occurrence of relapse after end of treatment. Primary endpoint is pyrazinamide AUC0-24h and main secondary endpoint is safety.

Ethics and dissemination

The study is approved by the Swedish Ethical Review Authority and the Swedish Medical Products Agency. Informed written consent is collected before study enrolment. The study results will be submitted to a peer-reviewed journal.

Trial registration number

NCT04694586.
Peripheral intravenous cannulation decision-making in emergency settings: a qualitative descriptive study
Authors: Evison Hugo , Carrington Mercedes , Keijzers Gerben , Marsh Nicole M , Sweeny Amy Lynn , Byrnes Joshua , Rickard Claire M , Carr Peter J , Ranse Jamie
Published: March 2022

Objectives

Rates of unused (‘idle’) peripheral intravenous catheters (PIVCs) are high but can vary per setting. Understanding factors that influence the decision-making of doctors, nurses and paramedics in the emergency setting regarding PIVC insertion, and what factors may modify their decision is essential to identify opportunities to reduce unnecessary cannulations and improve patient-centred outcomes. This study aimed to understand factors associated with clinicians’ decision-making on whether to insert or use a PIVC in the emergency care setting.

Design

A qualitative descriptive study using in-depth semistructured interviews and thematic analysis.

Setting

Gold Coast, Queensland, Australia, in a large tertiary level emergency department (ED) and local government ambulance service.

Participants

Participants recruited were ED clinicians (doctors, nurses) and paramedics who regularly insert PIVCs.

Results

From the 15 clinicians interviewed 4 key themes:knowledge and experience, complicated and multifactorial,convenience, anticipated patient clinical course,and several subthemes emerged relating to clinician decision-making across all disciplines. The first two themes focused on decision-making to gather data and evidence, such asknowledge and experience, and decisions beingcomplicated and multifactorial. The remaining two themes related to the actions clinicians took such asconvenienceandanticipated patient clinical course.

Conclusion

The decision to insert a PIVC is more complicated than clinicians, administrators and policy-makers may realise. When explored, clinician decisions were multifaceted with many factors influencing the decision to insert a PIVC. In actual practice, clinicians routinely insert PIVCs in most patients as a learnt reflex with little cognitive input. When considering PIVC insertion, more time needs to be devoted to the awareness of: (1) decision-making in the context of the clinician’s own experience, (2) cognitive biases and (3) patient-centred factors. Such awareness will support an appropriate risk assessment which will benefit the patient, clinician and healthcare system.
Uptake of the multi-arm multi-stage (MAMS) adaptive platform approach: a trial-registry review of late-phase randomised clinical trials
Authors: Noor Nurulamin M , Love Sharon B , Isaacs Talia , Kaplan Richard , Parmar Mahesh K B , Sydes Matthew R
Published: March 2022

Background

For medical conditions with numerous interventions worthy of investigation, there are many advantages of a multi-arm multi-stage (MAMS) platform trial approach. However, there is currently limited knowledge on uptake of the MAMS design, especially in the late-phase setting. We sought to examine uptake and characteristics of late-phase MAMS platform trials, to enable better planning for teams considering future use of this approach.

Design

We examined uptake of registered, late-phase MAMS platforms in the EU clinical trials register, Australian New Zealand Clinical Trials Registry, International Standard Randomised Controlled Trial Number registry, Pan African Clinical Trials Registry, WHO International Clinical Trial Registry Platform and databases: PubMed, Medline, Cochrane Library, Global Health Library and EMBASE. Searching was performed and review data frozen on 1 April 2021. MAMS platforms were defined as requiring two or more comparison arms, with two or more trial stages, with an interim analysis allowing for stopping of recruitment to arms and typically the ability to add new intervention arms.

Results

62 late-phase clinical trials using an MAMS approach were included. Overall, the number of late-phase trials using the MAMS design has been increasing since 2001 and been accelerated by COVID-19. The majority of current MAMS platforms were either targeting infectious diseases (52%) or cancers (29%) and all identified trials were for treatment interventions. 89% (55/62) of MAMS platforms were evaluating medications, with 45% (28/62) of the MAMS platforms having at least one or more repurposed medication as a comparison arm.

Conclusions

Historically, late-phase trials have adhered to long-established standard (two-arm) designs. However, the number of late-phase MAMS platform trials is increasing, across a range of different disease areas. This study highlights the potential scope of MAMS platform trials and may assist research teams considering use of this approach in the late-phase randomised clinical trial setting.

PROSPERO registration number

CRD42019153910.
Analysis of the relationship between sex and prescriptions for guideline-recommended therapy in peripheral arterial disease, in relation to 1-year all-cause mortality: a primary care cohort study
Authors: Benson Ruth A , Okoth Kelvin , Keerthy Deepiksana , Gokhale Krishna , Adderley Nicola J , Nirantharakumar Krishnarajah , Lasserson Daniel S
Published: March 2022

Objectives

To explore population patterns of sex-based incidence and prevalence of peripheral arterial disease (PAD), guideline-directed best medical therapy prescriptions and its relationship with all-cause mortality at 1 year.

Design

A retrospective cohort study.

Setting

Anonymised electronic primary care from 787 practices in the UK, or approximately 6.2% of the UK population.

Participants

All registered patients over 40 with a documented diagnosis of peripheral arterial disease.

Outcome measure

Population incidence and prevalence of PAD by sex. Patterns of guideline-directed therapy, and correlation with all-cause mortality at 1 year (defined as death due to any outcome) in patients with and without an existing diagnosis of cardiovascular disease. Covariates included Charlson comorbidity, sex, age, body mass index, Townsend score of deprivation, smoking status, diabetes, hypertension, statin and antiplatelet prescription.

Results

Sequential cross-sectional studies from 2010 to 2017 found annual PAD prevalence (12.7–14.3 vs 25.6 per 1000 in men) and incidence were lower in women (11.6–12.4 vs 22.7–26.8 per 10 000 person years in men). Cox proportional hazards models created for PAD patients with and without cardiovascular disease over one full year analysed 25 121 men and 13 480 women, finding that following adjustment for age, women were still less likely to be on a statin (OR 0.69; 95% CI 0.66 to 0.72; p<0.001) or antiplatelet (OR: 0.87; 95% CI 0.83 to 0.90; p<0.001). Once fully adjusted for guideline recommended medical therapy, all-cause mortality was similar between women and men (adjusted HR (aHR) 0.95, 95% CI 0.87 to 1.03, p=0.198 for all patients, aHR 1.01, 95% CI 0.88 to 1.16, p=0.860 for those with cardiovascular disease).

Conclusions

Women with a new diagnosis of PAD were not prescribed guideline-directed therapy at the same rate as men. However once adjusted for factors including age, all-cause mortality in men and women was similar.
Short-term effectiveness of nutrition therapy to treat type 2 diabetes in low-income and middle-income countries: systematic review and meta-analysis of randomised controlled trials
Authors: Guilbert Elizabeth , Perry Rachel , Whitmarsh Alex , Sauchelli Sarah
Published: March 2022

Objectives

This review examined the evidence arising from randomised controlled trials regarding the impact of nutrition therapy on glycaemic control in people living with type 2 diabetes mellitus (T2DM) in low/middle-income countries (LMICs).

Design

Systematic review and meta-analysis using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Approach.

Data sources

MEDLINE, EMBASE, Web of Science, OpenGrey and the International Clinical Trials Registry were searched (up to July 3 2020).

Eligibility criteria

Trials were included if they evaluated nutrition therapy in adults diagnosed with T2DM, were conducted in LMICs, measured glycaemic control and the trial included a 3-month post-intervention assessment. Nutrition therapy was defined according to American Diabetes Association recommendations.

Data extraction and synthesis

Two independent reviewers screened the database. Study characteristics and outcome data were extracted using a data collection form. Meta-analyses were conducted for glycated haemoglobin (HbA1c) and fasting blood glucose. Trials were assessed for risk of bias (Cochrane Risk-of-Bias, Version 2.0) and overall certainty of evidence (GRADE).

Results

Four trials met inclusion criteria (total n=463), conducted in Malaysia, Iran and South Africa. All trials focused on nutrition education with no direct prescription or manipulation of diet. Mean differences between intervention and standard care were −0.63% (95% CI −1.47% to 0.21%) for HbA1c and −13.63 mg/dL (95% CI −37.61 to 10.34) for fasting blood glucose in favour of the intervention. Given the small number of eligible trials, moderate to high risk of publication bias and serious concerns regarding consistency and precision of the evidence, certainty of evidence was deemed to be very low.

Conclusions

There is a lack of well-conducted randomised controlled trials that examine the long-term impact of nutrition therapy in LMICs, preventing firm conclusions to be made on their effectiveness. Further research is essential to discover realistic, evidence-based solutions.

PROSPERO registration number

CRD42020188435.
Relationships between overwork, burnout and suicidal ideation among resident physicians in hospitals in Japan with medical residency programmes: a nationwide questionnaire-based survey
Authors: Ishikawa Masatoshi
Published: March 2022

Objectives

This study examined the relationships between overwork, burnout and suicidal ideation among resident physicians working in hospitals throughout Japan.

Design

A nationwide, questionnaire-based survey.

Setting

Participating hospitals (n=416) were accredited by the Japanese Medical Specialty Board to offer medical residency programmes in 19 core specialties. Surveys were conducted in October 2020.

Participants

Valid responses were obtained from 4306 physicians (response rate: 49%).

Outcome measures

Items pertaining to the Japanese Burnout Scale, depressive tendencies and suicidal ideation were included in questionnaires. Multiple regression analyses were performed: suicidal ideation was the response variable; sex, age, core specialty, marital status, income, weekly working hours and workplace (ownership, number of beds, number of full-time physicians and regional classification) were explanatory variables.

Results

Regarding the Japanese Burnout Scale, the highest score was recorded for ‘sense of personal accomplishment’, followed by ‘emotional exhaustion’ and ‘depersonalization’. Increased emotional exhaustion and depersonalisation were associated with longer working hours, but there was no such trend for sense of personal accomplishment. Depressive tendencies and suicidal ideation were noted in 24.1% and 5.6% of respondents, respectively. These percentages tended to increase when respondents worked longer hours. Several factors were significantly associated with suicidal ideation: female sex (reference: male, OR: 2.08, 95% CI: 1.56 to 2.77), ≥12 million yen income (reference: <2 million yen, OR: 0.21, 95% CI: 0.05 to 0.79), ≥100 working hours/week (reference:<40 hours/week, OR: 3.64, 95% CI: 1.88 to 7.04) and 600–799 hospital beds (reference: <200 beds, OR: 0.23, 95% CI: 0.07 to 0.82).

Conclusions

Many Japanese residents demonstrated a tendency to experience burnout and suicidal ideation. Female sex, low income, long working hours and insufficient hospital beds were associated with suicidal ideation. To ensure physicians’ health and patients’ safety, it is necessary to advance workstyle reform for physicians.
Aetiology of lobar pneumonia determined by multiplex molecular analyses of lung and pleural aspirate specimens in the Gambia: findings from population-based pneumonia surveillance
Authors: Mackenzie Grant Austin , McLellan Jessica , Machuka Eunice , Ndiaye Malick , Pathirana Jayani , Fombah Augustin , Abatan Baderinwa , Hossain Ilias , Manjang Ahmed , Greenwood Brian , Hill Philip
Published: March 2022

Objectives

To determine the causes of lobar pneumonia in rural Gambia.

Design and setting

Population-based pneumonia surveillance at seven peripheral health facilities and two regional hospitals in rural Gambia. 7-valent pneumococcal conjugate vaccine (PCV7) was introduced routinely in August 2009 and replaced by PCV13 from May 2011.

Methods

Prospective pneumonia surveillance was undertaken among all ages with referral of suspected pneumonia cases to the regional hospitals. Blood culture and chest radiographs were performed routinely while lung or pleural aspirates were collected from selected, clinically stable patients with pleural effusion on radiograph and/or large, dense, peripheral consolidation. We used conventional microbiology, and from 8 April 2011 to 17 July 2012, used a multiplex PCR assay on lung and pleural aspirates. We calculated proportions with pathogens, associations between coinfecting pathogens and PCV effectiveness.

Participants

2550 patients were admitted with clinical pneumonia; 741 with lobar pneumonia or pleural effusion. We performed 181 lung or pleural aspirates and multiplex PCR on 156 lung and 4 pleural aspirates.

Results

Pathogens were detected in 116/160 specimens, the most common being Streptococcus pneumoniae(n=68), Staphylococcus aureus (n=26) and Haemophilus influenzae type b (n=11). Bacteria (n=97) were more common than viruses (n=49). Common viruses were bocavirus (n=11) and influenza (n=11). Coinfections were frequent (n=55). Moraxella catarrhalis was detected in eight patients and in every case there was coinfection with S. pneumoniae. The odds ratio of vaccine-type pneumococcal pneumonia in patients with two or three compared with zero doses of PCV was 0.17 (95% CI 0.06 to 0.51).

Conclusions

Lobar pneumonia in rural Gambia was caused primarily by bacteria, particularly S. pneumoniae and S. aureus. Coinfection was common and M. catarrhalis always coinfected with S. pneumoniae. PCV was highly efficacious against vaccine-type pneumococcal pneumonia.
Excess all-cause deaths stratified by sex and age in Peru: a time series analysis during the COVID-19 pandemic
Authors: Ramírez-Soto Max Carlos , Ortega-Cáceres Gutia , Arroyo-Hernández Hugo
Published: March 2022

Background

In this study, we estimated excess all-cause deaths and excess death rates during the COVID-19 pandemic in 25 Peruvian regions, stratified by sex and age group.

Design

Cross-sectional study.

Setting

Twenty-five Peruvian regions with complete mortality data.

Participants

Annual all-cause official mortality data set from SINADEF (Sistema Informático Nacional de Defunciones) at the Ministry of Health of Peru for 2017–2020, disaggregated by age and sex.

Main outcome measures

Excess deaths and excess death rates (observed deaths vs expected deaths) in 2020 by sex and age (0–29, 30–39, 40–49, 50–59, 60–69, 70–79 and ≥80 years) were estimated using P-score. The ORs for excess mortality were summarised with a random-effects meta-analysis.

Results

In the period between January and December 2020, we estimated an excess of 68 608 (117%) deaths in men and 34 742 (69%) deaths in women, corresponding to an excess death rate of 424 per 100 000 men and 211 per 100 000 women compared with the expected mortality rate. The number of excess deaths increased with age and was higher in men aged 60–69 years (217%) compared with women (121%). Men between the ages of 40 and 79 years experienced twice the rate of excess deaths compared with the expected rate. In eight regions, excess deaths were higher than 100% in men, and in seven regions excess deaths were higher than 70% in women. Men in eight regions and women in one region had two times increased odds of excess death than the expected mortality. There were differences in excess mortality according to temporal distribution by epidemiological week.

Conclusion

Approximately 100 000 excess all-cause deaths occurred in 2020 in Peru. Age-stratified excess death rates were higher in men than in women. There was strong excess in geographical and temporal mortality patterns according to region.