bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Ensemble of Multi-Kernel Gaussian Process Regressions Based on Heuristic Model Screening for Nonparametric Modeling of Ship Maneuvering Motion
Authors: Jiang Lichao , Shang Xiaobing , Qi Xinyu , Ouyang Zilu , Zhang Zhi
Published: February 2024

Gaussian process regression (GPR) is a commonly used approach for establishing the nonparametric models of ship maneuvering motion, and its performance depends on the selection of the kernel function. However, no single kernel function can be universally applied to all nonparametric models of ship maneuvering motion, which may compromise the robustness of GPR. To address this issue, an adaptive ensemble of multi-kernel GPRs based on heuristic model screening (AEGPR-HMS) is proposed in this paper. In the proposed method, four kernel functions are involved in constructing the ensemble model. The HMS method is introduced to determine the weights of individual-based GPR models, which can be adaptively assigned according to the baseline GPR model. To determine the hyper-parameters of these kernel functions, the genetic algorithm is also employed to compute the optimal values. The KVLCC2 tanker provided by the SIMMAN 2008 workshop is used to validate the performance of the proposed method. The results demonstrate that the AEGPR-HMS is an efficient and robust method for nonparametric modeling of ship maneuvering motion.
Sport and Exercise Psychology and Women’s Sport/Physical Activity Across Generations: Perspectives From Pre-Title IX Boomer Through Millennial to Post-Title IX Gen Z
Authors: Borum Kira , Reifsteck Erin J. , Gill Diane L.
Published: February 2024

Our author team represents three distinct generations, including an early Baby Boomer senior scholar, a Millennial mid-career scholar-professional, and a recent Gen Z graduate student. All three of us have been involved in sport and exercise psychology (SEP) from a feminist and social justice perspective during our academic careers and have traversed the intersections of these disciplines in our SEP practice and scholarship. In our conversations, we discuss the evolution of women’s place in sport/physical activity and SEP over time and situate our experiences across varied generations and positionalities, including highlighting our connections to, and the unique role of, our home institution. In those conversations, we acknowledge the progress that has been made while recognizing the ways in which sport/physical activity and SEP remain contested spaces. We conclude with our reflections and thoughts on moving forward to address diversity, equity, inclusion, and social justice for participants, practitioners, and scholars.
Amoebicidal effect of synthetic indoles against
Acanthamoeba
spp.: a study of cell death
Authors: Sifaoui Ines , Rodríguez-Expósito Rubén L. , Reyes-Batlle María , Dumpiérrez Ramos Alejandra , Diana-Rivero Raquel , García-Tellado Fernando , Tejedor David , Piñero José E. , Lorenzo-Morales Jacob
Published: February 2024

Organic and synthetic chemistry plays a crucial role in drug discovery fields. Moreover, chemical modifications of available molecules to enhance their efficacy, selectivity and safety have been considered as an attractive approach for the development of new bioactive agents. Indoles, a versatile group of natural heterocyclic compounds, have been widely used in pharmaceutical industry due to their broad spectrum of activities including antimicrobial, antitumoral and anti-inflammatory among others. Herein, we report the amoebicidal activity of different indole analogs on
Acanthamoeba castellanii
Neff. Among the 40 tested derivatives, eight molecules were able to inhibit this protistan parasite. The structure-activity relationship (SAR) analysis of their anti-
Acanthamoeba
activity would suggest that a carboxylation of C-3 position and the incorporation of halogen as chlorine/fluorine would enhance their biological profile, presumably by increasing their lipophilicity and therefore their ability to cross the cell membrane. Fluorescence image base system was used to investigate the effect of indole 6o c-6 on the cytoskeleton network and various programmed cell death features. We were able to highlight that the methyl 6-chloro-1H-indole-3-carboxylate could induce program cell death by the mitochondrial dysfunction.
Identification of bacterial dissimilatory antimonate reductase AnrA: genes and proteins involved in antimonate respiration and resistance in
Geobacter
sp. strain SVR
Authors: Kambara Ryoya , Yamamura Shigeki , Amachi Seigo
Published: February 2024

Geobacter
sp. strain SVR uses antimonate [Sb(V)] as a terminal electron acceptor for anaerobic respiration. Here, we visualized a possible key enzyme, periplasmic Sb(V) reductase (Anr), via active staining and non-denaturing gel electrophoresis. Liquid chromatography-tandem mass spectrometry analysis revealed that a novel dimethyl sulfoxide (DMSO) reductase family protein, WP_173201954.1, is involved in Anr. This protein was closely related with AnrA, a protein suggested to be the catalytic subunit of a respiratory Sb(V) reductase in
Desulfuribacillus stibiiarsenatis
. The
anr
genes of strain SVR (
anrXSRBAD
) formed an operon-like structure, and their transcription was upregulated under Sb(V)-respiring conditions. The expression of
anrA
gene was induced by more than 1 µM of antimonite [Sb(III)]; however, arsenite [As(III)] did not induce the expression of
anrA
gene. Tandem mass tag-based proteomic analysis revealed that, in addition to Anr proteins, proteins in the following categories were upregulated under Sb(V)-respiring conditions: (i) Sb(III) efflux systems such as Ant and Ars; (ii) antioxidizing proteins such as ferritin, rubredoxin, and thioredoxin; (iii) protein quality control systems such as HspA, HslO, and DnaK; and (iv) DNA repair proteins such as UspA and UvrB. These results suggest that strain SVR copes with antimony stress by modulating pleiotropic processes to resist and actively metabolize antimony. To the best of our knowledge, this is the first report to demonstrate the involvement of AnrA in Sb(V) respiration at the protein level. Furthermore, this is the first example to show high expression of the Ant system proteins in the Sb(V)-respiring bacterium.

IMPORTANCE

Antimony (Sb) exists mainly as antimonite [Sb(III)] or antimonate [Sb(V)] in the environment, and Sb(III) is more toxic than Sb(V). Recently, microbial involvement in Sb redox reactions has received attention. Although more than 90 Sb(III)-oxidizing bacteria have been reported, information on Sb(V)-reducing bacteria is limited. Especially, the enzyme involved in dissimilatory Sb(V) reduction, or Sb(V) respiration, is unclear, despite this pathway being very important for the circulation of Sb in nature. In this study, we demonstrated that the Sb(V) reductase (Anr) of an Sb(V)-respiring bacterium (
Geobacter
sp. SVR) is a novel member of the dimethyl sulfoxide (DMSO) reductase family. In addition, we found that strain SVR copes with Sb stress by modulating pleiotropic processes, including the Ant and Ars systems, and upregulating the antioxidant and quality control protein levels. Considering the abundance and diversity of putative
anr
genes in the environment, Anr may play a significant role in global Sb cycling in both marine and terrestrial environments.
Recapitulation of the Powassan virus life cycle in cell culture
Authors: Song Jingwei , Hong Jiayao , Yang Chen , Zhang Yu , Li Zhuoyang , He Peifeng , Ding Qiang
Published: February 2024

Powassan virus (POWV) is a tick-borne flavivirus known for causing fatal neuroinvasive diseases in humans. Recently, there has been a noticeable increase in POWV infections, emphasizing the urgency of understanding viral replication, pathogenesis, and developing interventions. Notably, there are no approved vaccines or therapeutics for POWV, and its classification as a biosafety level-3 (BSL-3) agent hampers research. To overcome these obstacles, we developed a replicon system, a self-replicating RNA lacking structural proteins, making it safe to operate in a BSL-2 environment. We constructed a POWV replicon carrying the Gaussia luciferase (Gluc) reporter gene and blasticidin (BSD) selectable marker. Continuous BSD selection led to obtain a stable POWV replicon-carrying Huh7 cell lines. We identified cell culture adaptive mutations G4079A, G4944T and G6256A, resulting in NS2A
R195K
, NS3
G122G
, and NS3
V560M
, enhancing RNA replication. We demonstrated the utility of the POWV replicon system for high-throughput screening (HTS) assay to identify promising antivirals against POWV replication. We further explored the applications of the POWV replicon system, generating single-round infectious particles (SRIPs) by transfecting Huh7-POWV replicon cells with plasmids encoding viral capsid (C), premembrane (prM), and envelope (E) proteins, and revealed the distinct antigenic profiles of POWV with ZIKV. In summary, the POWV replicon and SRIP systems represent crucial platforms for genetic and functional analysis of the POWV life cycle and facilitating the discovery of antiviral drugs.

IMPORTANCE

In light of the recent surge in human infections caused by POWV, a biosafety level-3 (BSL-3) classified virus, there is a pressing need to understand the viral life cycle and the development of effective countermeasures. To address this, we have pioneered the establishment of a POWV RNA replicon system and a replicon-based POWV SRIP system. Importantly, these systems are operable in BSL-2 laboratories, enabling comprehensive investigations into the viral life cycle and facilitating antiviral screening. In summary, these useful tools are poised to advance our understanding of the POWV life cycle and expedite the development of antiviral interventions.
RpoS and the bacterial general stress response
Authors: Bouillet Sophie , Bauer Taran S. , Gottesman Susan
Published: February 2024

The general stress response (GSR) is a widespread strategy developed by bacteria to adapt and respond to their changing environments. The GSR is induced by one or multiple simultaneous stresses, as well as during entry into stationary phase and leads to a global response that protects cells against multiple stresses. The alternative sigma factor RpoS is the central GSR regulator in
E. coli
and conserved in most γ-proteobacteria. In
E. coli
, RpoS is induced under conditions of nutrient deprivation and other stresses, primarily via the activation of RpoS translation and inhibition of RpoS proteolysis. This review includes recent advances in our understanding of how stresses lead to RpoS induction and a summary of the recent studies attempting to define RpoS-dependent genes and pathways.
Draft genome sequence of antibiotic-resistant
Shigella
flexneri
MTR_GR_V146 strain isolated from a tomato (
Solanum lycopersicum
) sample collected from a peri-urban area of Bangladesh
Authors: Islam Md. Saiful , Pramanik Pritom Kumar , Rana Md. Liton , Ullah Md. Ashek , Neloy Fahim Haque , Ramasamy Srinivasan , Schreinemachers Pepijn , Oliva Ricardo , Rahman Md. Tanvir
Published: February 2024

This study announces the genome sequence of the
Shigella flexneri
MTR_GR_V146 strain isolated from a tomato (
Solanum lycopersicum
) sample in Bangladesh. This strain has a 4,624,521 bp genome length (coverage: 73.07×), 2 CRISPR arrays, 1 plasmid, 52 predicted antibiotic resistance genes, and 53 virulence factor genes.
Earliest observation of the tetracycline destructase
tet(X3
)
Authors: Grenier Frédéric , Lévesque Simon , Rodrigue Sébastien , Haraoui Louis-Patrick
Published: February 2024

Tigecycline is an antibiotic of last resort for infections with carbapenem-resistant
Acinetobacter baumannii
. Plasmids harboring variants of the tetracycline destructase gene
tetX
promote rising tigecycline resistance rates. We report the earliest observation of
tet(X3
) in a clinical strain predating tigecycline’s commercialization, suggesting selective pressures other than tigecycline contributed to its emergence.

IMPORTANCE

We present the earliest observation of a
tet
(
X3
)-positive bacterial strain, predating by many years the earliest reports of this gene so far. This finding is significant as tigecycline is an antibiotic of last resort for carbapenem-resistant
Acinetobacter baumannii
(CRAB), which the World Health Organization ranks as one of its top three critical priority pathogens, and
tet
(
X3
) variants have become the most prevalent genes responsible for enabling CRAB to become tigecycline resistant. Moreover, the
tet
(
X3
)-positive strain we report is the first and only to be found that predates the commercialization of tigecycline, an antibiotic that was thought to have contributed to the emergence of this resistance gene. Understanding the factors contributing to the origin and spread of novel antibiotic resistance genes is crucial to addressing the major global public health issue, which is antimicrobial resistance.
Diagnostic utility of point-of-care ultrasound and optical coherence tomography for papilloedema in children: a prospective pilot study
Authors: Chiu Hannah H , Al-Farsi Nouf , Wong Agnes M F , Davis Adrienne , Tessaro Mark O , Wan Michael J
Published: February 2024

Background/Aims

Papilloedema is an important sign of serious neurological disease, but it can be difficult to detect on funduscopy. The purpose of this study was to determine the diagnostic accuracy of point-of-care ultrasound (POCUS) and optical coherence tomography (OCT) for detecting papilloedema in children.

Methods

This was a prospective observational study at a tertiary care paediatric hospital. Patients were eligible for the study if they underwent a lumbar puncture with opening pressure and had high-quality POCUS and OCT imaging.

Results

A total of 63 eyes from 32 patients were included in the study, 41 (65%) with papilloedema and 22 (35%) without. There were statistically significant differences between the groups in the optic disc elevation (ODE) (p<0.001) and optic nerve sheath diameter (ONSD) (p<0.001) on POCUS, and in the average retinal nerve fibre layer (rNFL) thickness on OCT (p<0.001). Average rNFL thickness had the highest diagnostic accuracy with an area under the curve (AUC) of 0.999 and a 100% sensitivity and 95% specificity for papilloedema (threshold value of ≥108 µm). ODE had an AUC of 0.866 and a 93% sensitivity and 55% specificity (threshold value of ≥0.5 mm). ONSD had an AUC of 0.786 and a 93% sensitivity and 45% specificity (threshold value of ≥5.5 mm).

Conclusion

Both OCT and POCUS are potentially useful tools to help diagnose papilloedema in children. Larger studies are needed to further define the role and accuracy of POCUS and OCT in assessing papilloedema in children.
Aerobic exercise interventions for promoting cardiovascular health and mobility after stroke: a systematic review with Bayesian network meta-analysis
Authors: Moncion Kevin , Rodrigues Lynden , Wiley Elise , Noguchi Kenneth S , Negm Ahmed , Richardson Julie , MacDonald Maureen Jane , Roig Marc , Tang Ada
Published: February 2024

Objective

To determine the superiority of aerobic exercise (AE) interventions on key outcomes of stroke recovery, including cardiorespiratory fitness (V̇O2peak, primary outcome), systolic blood pressure (SBP) and mobility (6 min Walk Test (6MWT) distance and 10 m Usual Gait Speed) after stroke.

Data sources

MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL, SPORTDiscus, PsycINFO and AMED Allied and Complementary Medicine were searched from inception to February 2023.

Eligibility criteria

Randomised controlled trials were included that compared the effects of any AE interventions (low-intensity, moderate-intensity, high-intensity continuous training (HICT), high-intensity interval training (HIIT)) to no exercise, usual care or other AE interventions in individuals poststroke.

Analyses

Systematic review with Bayesian network meta-analysis (NMA) methodology was employed. Surface under the cumulative ranking curve (SUCRA) values were used to rank interventions. The Grading of Recommendations, Assessment, Development and Evaluation minimally contextualised framework for NMA was followed.

Results

There were 28 studies (n=1298) included in the NMA for V̇O2peak, 11 (n=648) for SBP, 28 (n=1494) for 6MWT and 18 (n=775) for the 10 m Usual Gait Speed. The greatest effect on V̇O2peak, 6MWT and 10 m Usual Gait Speed was observed after HIIT and HICT. No differences between interventions were found for SBP. SUCRA values identified HIIT as the superior AE intervention for all outcomes of interest. HIIT was the most effective intervention for improving V̇O2peak (2.9 mL/kg/min (95% credible interval 0.8 to 5.0) moderate certainty) compared with usual care.

Conclusion

This NMA suggests that higher-intensity AE is superior to traditional low-intensity to moderate-intensity AE for improving outcomes after stroke.
Access to telehealth and changes in diabetes care patterns during the pandemic: evidence from a large integrated health system in the Southeast USA
Authors: Oviedo Sofia A , McDonald Bennett , Gander Jennifer C , Ali Mohammed K , Harding Jessica L
Published: February 2024

Introduction

To examine the role of telehealth in diabetes care and management during versus pre-COVID-19 pandemic.

Research design and methods

We included adults (≥18 years) with prevalent diabetes as of January 1, 2018, and continuously enrolled at Kaiser Permanente Georgia through December 31, 2021 (n=22,854). We defined pre (2018–2019) and during COVID-19 (2020–2021) periods. Logistic generalized estimating equations (GEEs) assessed the within-subject change in adherence to seven annual routine care processes (blood pressure (BP), hemoglobin A1C (HbA1c), cholesterol, creatinine, urine-albumin-creatinine ratio (UACR), eye and foot examinations) pre versus during COVID-19 among telehealth users (ie, more than one telehealth visit per year per period) and non-telehealth users. Linear GEE compared mean laboratory measurements pre versus during COVID-19 by telehealth use.

Results

The proportion of telehealth users increased from 38.7% (2018–2019) to 91.5% (2020–2021). During (vs pre) the pandemic, adherence to all care processes declined in telehealth (range: 1.6% for foot examinations to 12.4% for BP) and non-telehealth users (range: 1.9% for foot examinations to 40.7% for BP). In telehealth users, average HbA1c (mean difference: 0.4% (95% CI 0.2% to 0.6%), systolic BP (1.62 mm Hg (1.44 to 1.81)), and creatinine (0.03 mg/dL (0.02 to 0.04)), worsened during (vs pre) COVID-19, while low density lipoprotein (LDL) cholesterol improved (−9.08 mg/dL (−9.77 to −8.39)). For UACR, odds of elevated risk of kidney disease increased by 48% (OR 1.48 (1.36–1.62)). Patterns were similar in non-telehealth users.

Conclusions

Telehealth use increased during the pandemic and alleviated some of the observed declines in routine diabetes care and management.
Predictive biomarkers of rapidly developing insulin deficiency in children with type 1 diabetes
Authors: Lundkvist Per , Grönberg Annika , Carlsson Per-Ola , Ludvigsson Johnny , Espes Daniel
Published: February 2024

Introduction

The rate of progression to complete insulin deficiency varies greatly in type 1 diabetes. This constitutes a challenge, especially when randomizing patients in intervention trials aiming to preserve beta cell function. This study aimed to identify biomarkers predictive of either a rapid or slow disease progression in children with new-onset type 1 diabetes.

Research design and methods

A retrospective, longitudinal cohort study of children (<18 years) with type 1 diabetes (N=46) was included at diagnosis and followed until complete insulinopenia (C-peptide <0.03 nmol/L). Children were grouped into rapid progressors (n=20, loss within 30 months) and slow progressors (n=26). A sex-matched control group of healthy children (N=45) of similar age was included for comparison. Multiple biomarkers were assessed by proximity extension assay (PEA) at baseline and follow-up.

Results

At baseline, rapid progressors had lower C-peptide and higher autoantibody levels than slow. Three biomarkers were higher in the rapid group: carbonic anhydrase 9, corticosteroid 11-beta-dehydrogenase isozyme 1, and tumor necrosis factor receptor superfamily member 21. In a linear mixed model, 25 proteins changed over time, irrespective of group. One protein, a coxsackievirus B–adenovirus receptor (CAR) increased over time in rapid progressors. Eighty-one proteins differed between type 1 diabetes and healthy controls. Principal component analysis could not distinguish between rapid, slow, and healthy controls.

Conclusions

Despite differences in individual proteins, the combination of multiple biomarkers analyzed by PEA could not distinguish the rate of progression in children with new-onset type 1 diabetes. Only one marker was altered significantly when considering both time and group effects, namely CAR, which increased significantly over time in the rapid group. Nevertheless, we did find some markers that may be useful in predicting the decline of the C-peptide. Moreover, these could potentially be important for understanding type 1 diabetes pathogenesis.
Exposure to school-based tobacco prevention interventions in low-income and middle-income countries and its association with psychosocial predictors of smoking among adolescents: a pooled cross-sectional analysis of Global Youth Tobacco Survey data from 38 countries
Authors: Chido-Amajuoyi Onyema Greg , Osaghae Ikponmwosa , Agaku Israel Terungwa , Chen Baojiang , Mantey Dale S
Published: February 2024

Objectives

To describe the prevalence of school-based tobacco prevention programme exposure among adolescents in low-income and middle-income countries (LMICs) and its association with psychosocial predictors of smoking.

Design

Analysis of pooled cross-sectional data.

Setting

Global Youth Tobacco Survey (GYTS), conducted in 38 LMICs.

Participants

This was a pooled analysis of data involving a total of 132 755 adolescent respondents to GYTS in 38 LMICs across Africa, Europe and Central/South America between 2014 and 2017.

Exposure and outcome measures

The primary independent variable for this study was self-reported exposure to school-based tobacco prevention programmes in the past year. Five psychosocial determinants of smoking were explored as outcomes: perceived addictiveness of nicotine, perceived harm of secondhand smoke exposure, support for restricting cigarette smoking at public indoor locations, support for restricting cigarette smoking at public outdoor areas and self-reported prediction of enjoying cigarette smoking. Multivariable logistic regression models were used to examine the relationship between exposure to school-based tobacco prevention programmes and study outcomes, controlling for sociodemographic and smoking-related characteristics of respondents.

Results

Overall, 59.1% of adolescents in LMICs self-reported exposure to school-based tobacco prevention programmes. The country-specific prevalence of adolescent exposure to school-based tobacco interventions ranged from 24.9% in the Comoros to 99.3% in Turkmenistan. Exposure to school-based tobacco interventions was significantly associated with greater secondhand smoke harm perceptions (adjusted OR (AOR): 1.69; 95% CI: 1.69 to 1.70), perceptions of addictiveness (AOR: 1.37; 95% CI: 1.36 to 1.37) and supporting tobacco use restrictions indoors (AOR: 1.70; 95% CI: 1.69 to 1.70) and outdoors (AOR: 1.59; 95% CI: 1.59 to 1.60). Exposure to school-based tobacco interventions was associated with lower odds of anticipating enjoying cigarette smoking (AOR: 0.76; 95% CI: 0.76 to 0.76).

Conclusion

Exposure to tobacco prevention programmes in schools is suboptimal in LMICs. Given the protective associations described in this study from school-based tobacco prevention programme exposure, it is imperative that national governments implement school-based programmes into ongoing tobacco control measures.
Prediction of body mass index and skeletal maturity for early menarche risk at menarche onset: a cross-sectional study of Chinese girls
Authors: Li Yang , Wu Hua-Hong , Guo Jia-yun , Li Hui
Published: February 2024

Background

This study aimed to assess the predictive value of body mass index (BMI) and skeletal maturity for the occurrence of early menarche in Chinese girls.

Methods

A cross-sectional analysis was conducted on 785 girls aged 8.1–14.6 years who visited our hospital within 3 months of menarche onset. Early menarche was defined as menarche age (MA) <10 years. Skeletal maturity was classified based on the difference between bone age (BA) and chronological age (CA), termed BA-CA; advanced BA was defined as BA-CA>2 years.

Results

The average MA was 10.7 (SD: 1.1) years, with a prevalence of early menarche of 23.3%. BA exhibited relative stability compared with MA, with an average of 12.8 (SD: 0.5) years at menarche onset. At menarche onset, the average height, weight and BMI were 149.1 (SD: 5.1) cm, 43.3 (SD: 7.2) kg and 19.4 (SD: 2.8) kg/m², respectively. Logistic regression analyses indicated that every 1-year increment in BA-CA was independently associated with a 18.90-fold higher risk of early menarche (95% CI 11.77 to 30.32), respectively, and remained statistically significant even after adjusting for height or mid-parental height. Furthermore, the prediction of BA-CA for early menarche demonstrated a dose-dependent pattern across BMI categories, with the greatest risk observed in normal-weight girls, the lowest risk in obese girls and an intermediate risk in overweight girls at the same degree of BA advancement.

Conclusions

Our findings provide evidence supporting the significant contributions of BMI and skeletal maturity in predicting early menarche among Chinese girls at menarche onset. Additionally, the results suggest a dose-dependent relationship between skeletal maturity and BMI categories, with normal-weight girls displaying a higher risk of early menarche compared to overweight and obese girls with the same degree of BA advancement.
Assessing caregiver burden in advanced kidney disease: protocol for a systematic review of the measurement properties of instruments and tools
Authors: Shankar Ravi , Luo Nan , Lim Yee Wei , Khatri Priyanka , Leong Leanne , Teo Geraldine Yu-Xuan , Mukhopadhyay Amartya , Choo Jason , Chua Horng Ruey , Teng Gim-Gee , Phua Jason , Hong Wei Zhen
Published: February 2024

Introduction

Caregiver burden is a significant issue in the care of patients with advanced kidney disease. Its assessment is crucial for evaluating the needs of caregivers and for the development of interventions to support them. Several instruments have been developed to measure caregiver burden in these patients. However, the measurement properties of these instruments have not been systematically reviewed.

Methods and analysis

This systematic review will include a comprehensive search of databases including PubMed, CINAHL, Embase, Cochrane Library, SCOPUS and Web of Science by using keywords and MeSH terms to identify relevant studies starting from each database inception to 1 January 2024 and covering papers in English. The search strategy will combine relevant keywords and database-specific subject headings related to the following concepts: (1) caregivers, (2) burden, stress, distress, (3) chronic kidney disease, end-stage kidney disease, dialysis. Reference lists of eligible articles will also be hand searched. We will include quantitative and qualitative studies evaluating measurement properties of instruments assessing caregiver burden in caregivers of adult patients (aged ≥18 years). Data will be extracted from the selected studies and analysed using the COnsensus-based Standards for the selection of health Measurement INstruments checklist as the study quality assessment tool. Subsequently, the van der Vleuten utility index will be used to critique and categorise the instruments. A narrative that synthesises the utility of all instruments will be presented along with recommendations for the selection of instruments depending on specific clinical contexts. This systematic review will provide an overview of the measurement properties of available instruments, including discussion on reliability, validity and responsiveness. Results from the review may give rise to the subsequent development of most appropriate instrument that could be applied to the assessment of caregiver burden in advanced kidney disease.

Ethics and dissemination

Ethics approval is not required as this study will merely synthesise data from published studies. The results will be disseminated through peer-reviewed publications as well as conference presentations.

PROSPERO registration number

CRD42023433906.
Tobacco use and behaviour among South African adolescents and young adults: systematic review and meta-analysis
Authors: Londani Mukhethwa , Oladimeji Olanrewaju
Published: February 2024

Objective

Tobacco use, particularly the initiation of smoking during adolescence and young adulthood, represents a significant public health concern in South Africa. This study aims to conduct a comprehensive review of published literature about tobacco use and behaviour among adolescents and young adults and to determine an aggregated prevalence estimate of tobacco use within this demographic.

Design

Systematic review and meta-analysis.

Data sources

PubMed/MEDLINE, EMBASE, Cochrane Library, Scopus and Google Scholar were searched from 1 January 2000 through 31 October 2023.

Eligibility criteria

Studies were eligible for inclusion if they were cross-sectional studies conducted in South Africa and measured the prevalence and determinants of tobacco use among adolescents and young adults aged 12–24 years.

Data extraction and synthesis

Two reviewers independently extracted information for each article and saved it into an Excel spreadsheet. Risk of bias analysis was conducted using the Risk of Bias Assessment Tool for non-randomised studies. The methodology quality of each selected study was evaluated using the Joanna Briggs Institute checklist. The heterogeneity of prevalence estimates was assessed using I2statistic (random-effects DerSimonian-Laid approach).

Results

Out of 73 articles identified, 12 articles were included in the analysis. The pooled prevalence of current tobacco use among South African adolescents and young adults was estimated to be 22%. The pooled prevalence of tobacco use among school dropouts, university students and secondary school learners was 51%, 20% and 16%, respectively. Stratifying using gender, boys (26%) were two times more likely to use tobacco than girls (13%).

Conclusion

The elevated occurrence of tobacco usage among South African adolescents and young adults is a relevant public health concern. There is a need for more population-based prevalence studies at a national level to estimate the burden of tobacco use in South Africa.

PROSPERO registration number

CRD42023428369.
Risk factors for tuberculosis-related death among adults with drug-sensitive pulmonary tuberculosis in Selangor, Malaysia from 2013 to 2019: a retrospective cohort study using surveillance data
Authors: Suhairi Mohammad Haikal , Mohamad Mariam , Isa Mohamad Rodi , Mohd Yusoff Mas Ahmad Sherzkawee , Ismail Nurhuda
Published: February 2024

Objectives

Due to the paucity of literature on risk factors for tuberculosis (TB)-related death, we determine the sociodemographic and clinical risk factors associated with TB-related deaths among adult pulmonary TB (PTB) patients on treatment in Selangor, Malaysia.

Design

Retrospective cohort study.

Setting

Routinely collected primary care data from all government TB clinics in Selangor.

Participants

Data of 24 570 eligible adult PTB patients from 2013 to 2019 were obtained from Selangor’s State Health Department surveillance records. We included PTB patients aged at least 15 years old at the time of diagnosis with complete documentation of the dates of diagnosis, treatment initiation, end of treatment/follow-up and treatment outcomes. We excluded patients whose diagnoses were changed to non-TB, post-mortem TB diagnosis and multidrug-resistant TB (MDR-TB) patients.

Primary and secondary outcome measures

TB-related death, determined from the recorded physicians’ consensus during the TB mortality meeting.

Results

TB-related death was significantly associated with far (adjusted HR (aHR) 9.98, 95% CI 4.28 to 23.28) and moderately advanced (aHR 3.23, 95% CI 1.43 to 7.31) radiological findings at diagnosis; concurrent TB meningitis (aHR 7.67, 95% CI 4.53 to 12.98) and miliary TB (aHR 6.32, 95% CI 4.10 to 9.74) involvement; HIV positive at diagnosis (aHR 2.81, 95% CI 2.21 to 3.57); Hulu Selangor (aHR 1.95, 95% CI 1.29 to 2.93), Klang (aHR 1.53, 95% CI 1.18 to 1.98) and Hulu Langat (aHR 1.31, 95% CI 1.03 to 1.68) residing districts; no formal education (aHR 1.70, 95% CI 1.23 to 2.35); unemployment (aHR 1.54, 95% CI 1.29 to 1.84), positive sputum smear acid-fast bacilli (AFB) at diagnosis (aHR 1.51, 95% CI 1.22 to 1.85); rural residency (aHR 1.39, 95% CI 1.13 to 1.72) and advancing age (aHR 1.03, 95% CI 1.02 to 1.03).

Conclusions

Far and moderately advanced radiological findings, concurrent TB meningitis and miliary TB involvement, HIV positive, Hulu Selangor, Klang and Hulu Langat residing districts, no formal education, unemployment, positive sputum smear AFB, rural residency and advancing age are risk factors of TB-related death. Our findings should assist in identifying high-risk patients requiring interventions against TB-related death.
Prevalence of alcohol use and associated factors since COVID-19 among school-going adolescents within the Southern African Development Community: a systematic review protocol
Authors: Ntho Tshepo A , Themane Mahlapahlapana J , Sepadi Medwin D , Phochana Talamo S , Sodi Tholene , Quarshie Emmanuel Nii-Boye
Published: February 2024

Introduction

The COVID-19 pandemic has significantly shaped the global landscape and impacted various aspects of individuals’ lives, especially the behaviour of school-going adolescents regarding substance use. Among these substances, alcohol is the most predominant substance, particularly among school-going adolescents, who also are highly susceptible to harmful alcohol use, such as poor academic performance, psychiatric disorders and disrupted social lives. This review will synthesise the known prevalence estimates and associated factors of alcohol use among school-going adolescents in the Southern African Development Community (SADC) since the COVID-19 pandemic.

Methods and analysis

We will perform a systematic review in line with the Cochrane Handbook for Systematic Reviews. We will systematically search for selected global databases (ScienceDirect, EbscoHost, PsycINFO and PubMed) and regional electronic databases (African Index Medicus, Sabinet and African Journals OnLine). Peer-reviewed literature published between 11 March 2020 and 10 March 2024 will be considered for eligibility without language restriction. All 16 countries of the SADC region will be included in the review. The Mixed-Methods Appraisal Tool checklist for quality appraisal will be used to appraise the methodological quality of the included studies. Depending on the level of heterogeneity, prevalence estimates will be pooled in a meta-analysis; narrative synthesis will be applied to describe the reported associated factors of alcohol use.

Ethics and dissemination

We will not seek ethical approval from an institutional review board since the study will not involve gathering data directly from individual school-going adolescents, nor will it violate their privacy. When completed, the full report of this review will be submitted to a journal for peer-reviewed publication; the key findings will be presented at local and international conferences with a partial or full focus on (adolescent) alcohol (mis)use.

PROSPERO registration number

CRD42023452765.
Protocol for a randomised controlled trial comparing warfarin with no oral anticoagulation in patients with atrial fibrillation on chronic dialysis: the Danish Warfarin-Dialysis (DANWARD) trial
Authors: Ballegaard Ellen Linnea Freese , Lindhard Kristine , Lindhardt Morten , Peters Christian Daugaard , Thomsen Nielsen Finn , Tietze Ida Nørager , Borg Rikke , Boesby Lene , Bertelsen Marianne Camilla , Brøsen Julie Maria Bøggild , Cibulskyte-Ninkovic Donata , Rantanen Jesper Moesgaard , Mose Frank Holden , Kampmann Jan Dominik , Nielsen Alice Skovhede , Breinholt Johanne Kodal , Kofod Dea Haagensen , Bressendorff Iain , Clausen Peter Vilhelm , Lange Theis , Køber Lars , Kamper Anne-Lise , Bang Casper Niels Furbo , Torp-Pedersen Christian , Hansen Ditte , Grove Erik L , Gislason Gunnar , Dam Jensen Jens , Olesen Jonas Bjerring , Hornum Mads , Rix Marianne , Schou Morten , Carlson Nicholas
Published: February 2024

Introduction

Atrial fibrillation is highly prevalent in patients on chronic dialysis. It is unclear whether anticoagulant therapy for stroke prevention is beneficial in these patients. Vitamin K-antagonists (VKA) remain the predominant anticoagulant choice. Importantly, anticoagulation remains inconsistently used and a possible benefit remains untested in randomised clinical trials comparing oral anticoagulation with no treatment in patients on chronic dialysis. The Danish Warfarin-Dialysis (DANWARD) trial aims to investigate the safety and efficacy of VKAs in patients with atrial fibrillation on chronic dialysis. The hypothesis is that VKA treatment compared with no treatment is associated with stroke risk reduction and overall benefit.

Methods and analysis

The DANWARD trial is an investigator-initiated trial at 13 Danish dialysis centres. In an open-label randomised clinical trial study design, a total of 718 patients with atrial fibrillation on chronic dialysis will be randomised in a 1:1 ratio to receive either standard dose VKA targeting an international normalised ratio of 2.0–3.0 or no oral anticoagulation. Principal analyses will compare the risk of a primary efficacy endpoint, stroke or transient ischaemic attack and a primary safety endpoint, major bleeding, in patients allocated to VKA treatment and no treatment, respectively. The first patient was randomised in October 2019. Patients will be followed until 1 year after the inclusion of the last patient.

Ethics and dissemination

The study protocol was approved by the Regional Research Ethics Committee (journal number H-18050839) and the Danish Medicines Agency (case number 2018101877). The trial is conducted in accordance with the Helsinki declaration and standards of Good Clinical Practice. Study results will be disseminated to participating sites, at research conferences and in peer-reviewed journals.

Trial registration numbers

NCT03862859, EUDRA-CT 2018-000484-86 and CTIS ID 2022-502500-75-00.
Improving safety and preventing falls using an evidence-based, front-line staff huddling practice: protocol for a pragmatic trial to increase quality of care in State Veterans Homes
Authors: Nash Princess , Clark Valerie , McConnell Eleanor , Mills Whitney , Morgan Robert , Pimentel Camilla , Ritchey Katherine , Levy Cari , Snow A Lynn , Hartmann Christine
Published: February 2024

Introduction

Falls in nursing homes are a major cause for decreases in residents’ quality of life and overall health. This study aims to reduce resident falls by implementing the LOCK Falls Programme, an evidence-based quality improvement intervention. The LOCK Falls Programme involves the entire front-line care team in (1) focusing on evidence of positive change, (2) collecting data through systematic observation and (3) facilitating communication and coordination of care through the practice of front-line staff huddles.

Methods and analysis

The study protocol describes a mixed-methods, 4-year hybrid (type 2) effectiveness-implementation study in State Veterans Homes in the USA. The study uses a pragmatic stepped-wedge randomised trial design and employs relational coordination theory and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework to guide implementation and evaluation. A total of eight State Veterans Homes will participate and data will be collected over an 18-month period. Administrative data inclusive of all clinical assessments and Minimum Data Set assessments for Veterans with a State Veterans Home admission or stay during the study period will be collected (8480 residents total). The primary outcome is a resident having any fall. The primary analysis will be a partial intention-to-treat analysis using the rate of participants experiencing any fall. A staff survey (n=1200) and qualitative interviews with residents (n=80) and staff (n=400) will also be conducted. This research seeks to systematically address known barriers to nursing home quality improvement efforts associated with reducing falls.

Ethics and dissemination

This study is approved by the Central Institutional Review Board (#167059-11). All participants will be recruited voluntarily and will sign informed consent as required. Collection, assessment and managing of solicited and spontaneously reported adverse events, including required protocol alterations, will be communicated and approved directly with the Central Institutional Review Board, the data safety monitoring board and the Office of Research and Development. Study results will be disseminated through peer-reviewed publications and conference presentations at the Academy Health Annual Research Meeting, the Gerontological Society of America Annual Scientific Meeting and the American Geriatrics Society Annual Meeting. Key stakeholders will also help disseminate lessons learnt.

Trial registration number

NCT05906095.
Applying the lessons of design thinking: a unique programme of care for acutely unwell, community-dwelling COVID-19 patients
Authors: Devlin Megan K , McIntyre Natasha J , Ramer Matthew D , Kwon Young Han , Nicholson J Michael , Mrkobrada Marko , Kronick Jami , Calvin James E , Spicer Erin
Published: February 2024

Background

The COVID-19 pandemic limited access to primary care and in-person assessments requiring healthcare providers to re-envision care delivery for acutely unwell outpatients. Design thinking methodology has the potential to support the robust evolution of a new clinical model.

Aim

To demonstrate how design thinking methodology can rapidly and rigorously create and evolve a safe, timely, equitable and patient-centred programme of care, and to share valuable lessons for effective implementation of design thinking solutions to address complex problems.

Method

We describe how design thinking methodology was employed to create a new clinical model of care. Using the example of a novel telemedicine programme to support acutely unwell, community-dwelling COVID-19-positive patients called the London Urgent COVID-19 Care Clinic (LUC3), we show how continuous quality outcomes (safety, timeliness, equity and patient-centredness), as well as patient experience survey responses, can drive iterative changes in programme delivery.

Results

The inspiration phase identified four key needs for this patient population: monitoring COVID-19 signs and symptoms; self-managing COVID-19 symptoms; managing other comorbidities in the setting of COVID-19; and escalating care as needed. Guided by these needs, a cross-disciplinary stakeholder group was engaged in the ideation and implementation phases to create a unique and comprehensive telemedicine programme (LUC3). During the implementation phase, LUC3 assessed 2202 community-based patients diagnosed with acute COVID-19; the collected quality outcomes and end-user feedback led to evolution of programme delivery.

Conclusion

Design thinking methodology provided an essential framework and valuable lessons for the development of a safe, equitable, timely and patient-centred telemedicine care programme. The lessons learnt here—the importance of inclusive collaboration, using empathy to guide equity-focused interventions, leveraging continuous metrics to drive iteration and aiming for good-if-not-perfect plans—can serve as a road map for using design thinking for targeted healthcare problems.
Development of delivery indicators and delivery enablers for cardiovascular disease in the UK: a modified Delphi study
Authors: Gale Chris , Arden Chris , Bakhai Ameet , Grothier Lucy , Gray Huon H , Williams Helen
Published: February 2024

Introduction

Standards to define and measure quality in healthcare for cardiovascular disease risk reduction and secondary prevention are available, but there is a paucity of indicators that could serve as facilitators of structural change at a system level. This research study aimed to develop a range of delivery indicators to help cardiac clinical networks assess delivery of and progress towards cardiovascular disease objectives.

Methods

This study used an adapted version of the European Society of Cardiology’s four-step process for the development of quality indicators. The four steps in this study were as follows: identify critical factors of enablement, construct a list of candidate indicators, select a final set of indicators and assess availability of national data for each indicator. In this iterative process, a core project group of six members was supported by a wider review group of 21 people from the National Health Service (NHS) clinical and management personnel database.

Results

The core project group identified six relevant cardiovascular disease priorities in the NHS Long Term Plan and used an iterative process to identify 21 critical factors that impact on their implementation. A total of 57 potential indicators that could be measures of implementation were developed. The core project group agreed on a set of 38 candidate indicators that were circulated to the review group for rating. Based on these scores, the core project group excluded 5 indicators to arrive at a final set of 33 delivery indicators. National datasets were available for 22 of the final indicators, which were designated as delivery indicators. The remaining 11, for which national datasets were not available but locally available datasets could be used, were designated as delivery enablers.

Conclusion

The suite of delivery indicators and delivery enablers for cardiovascular disease could allow a more focused evaluation of factors that impact on delivery of healthcare for cardiovascular disease.