bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of receptor-binding protein and host receptor of non-lytic dsRNA phage phiNY
Authors: Ding Guoqing , Liu Hongmei , Lan Jing , Qian Tianbao , Zhou Yan , Zhu Tongyu , Zhang Tingting
Published: October 2024

To date, complete genome sequences of 14 double-stranded RNA (dsRNA) phages are available, and studies have shown that the host range of dsRNA phages is limited. The hosts of most dsRNA phages belong to the genus
Pseudomonas
. However, the dsRNA phage phiNY, which has a non-lytic life cycle, was isolated from
Microvirgula aerodenitrificans
. Currently, the interaction between dsRNA phage phiNY and its host bacteria is unclear, which is not beneficial to a comprehensive understanding of dsRNA phage biology and the exploitation of dsRNA phage with non-lytic life cycle for biomedical applications and others. Phage adsorption is a crucial step through the interactions between receptor-binding protein (RBP) of the phage and its receptors to initiate the infection process, which dictates host range specificity. Thus, we identified the RBP and host receptor of phiNY. Through homology alignment, amino acid sequence similarity analysis, and the phylogenetic tree analysis, orf11, located in the M-segment of dsRNA phage phiNY, encodes a putative RBP. We further performed the whole-cell enzyme-linked immunosorbent assay (ELISA), western blotting assay, and indirect immunofluorescence assay and demonstrated that this orf11 is an RBP. Finally, using affinity chromatography, ELISA, and dynamic light scattering, we identified lipopolysaccharides (LPSs) on the surface of the host
M. aerodenitrificans
strain LH9 as host receptors involved in the adsorption of the dsRNA bacteriophage phiNY and observed the state of phiNY RBP after combining with LPS by atomic force microscopy. These results will guide future studies on phage-host interaction in a dsRNA phage with a non-lytic life cycle.

IMPORTANCE

The interactions between the lytic dsRNA phages and their host receptors have been clarified in previous studies. However, the interaction between the dsRNA phage phiNY (which has a non-lytic life cycle) and its host receptors during the dsRNA phage adsorption process was unknown. Here, we found that phiNY uses the orf11 protein as a receptor-binding protein (RBP). In addition, we found that this orf11 recognizes lipopolysaccharide from the host bacterium
Microvirgula aerodenitrificans
strain LH9 as a speciﬁc receptor. These results suggest that phiNY, like lytic dsRNA phages, uses an RBP to bind to a similar host receptor (i.e., lipopolysaccharide). Determining the interaction between the dsRNA phage phiNY and its host receptors will help to elucidate the mechanisms underlying the phiNY non-lytic life cycle and enhance our understanding of its infection mechanism.
Evaluation of the Epitogen Lyme Detect IgG ELISA: a novel peptide multiplexing approach
Authors: Wang Tiehui , Wang Alex , Zindrili Rodanthi , Melis Elena , Guntupalli Swapna , Brittain-Long Robin , Delibegovic Mirela , Secombes Christopher J. , Mody Nimesh , Mavin Sally , Buks Ralfs
Published: October 2024

Lyme Borreliosis (LB), or Lyme disease, is a growing health concern caused by
Borrelia burgdorferi sensu lato
(Bbsl) bacteria transmitted through tick bites, and untreated cases can lead to severe health complications. Existing serology tests, while valuable, have low sensitivity in early infection stages where diagnosis is vital, interpretation variability, and false positives from cross-reactivity, while direct detection methods also suffer from low sensitivity, due to the inconsistent presence of Bbsl components in clinical samples. This study validated the diagnostic performance of the novel Epitogen Lyme Detect IgG enzyme-linked immunosorbent assay (ELISA) based on scaffold-displayed peptide antigens, using 120 specific immunodominant epitopes selected from 37 antigenic bacterial proteins corresponding to the main pathogenic Bbsl genospecies. Using 220 serum samples from Scottish patients with early, late, and disseminated LB, the assay’s sensitivity was compared with that of the LIAISON Borrelia IgG CLIA, while specificity was assessed with 198 control samples, including healthy individuals and patients with diseases that are humorally similar. The Epitogen Lyme Detect IgG assay demonstrated comparable performance to the LIAISON Borrelia IgG in disseminated and late LB (Lyme neuroborreliosis, acrodermatitis chronica atrophicans, and Lyme arthritis). Notably, the Epitogen Lyme Detect IgG showed significantly higher sensitivity in patients with suspected erythema migrans, while maintaining high specificity. The Epitogen Lyme Detect IgG ELISA offers a promising advancement in LB diagnostics, demonstrating its potential for more accurate and timely diagnosis, particularly in the early stages of LB infection.

IMPORTANCE

Lyme Borreliosis (LB), caused by
Borrelia burgdorferi sensu lato
bacteria, poses significant health risks if undiagnosed or diagnosed late. Current diagnostic tests have limitations, especially in early-stage detection. This study validates the Epitogen Lyme Detect IgG enzyme-linked immunosorbent assay, demonstrating superior sensitivity in early LB detection while maintaining high specificity. The Epitogen Lyme Detect IgG comprises a suite of 120 immunodominant IgG epitopes/peptides from 37 bacterial antigens, covering the main LB-causing species:
Borrelia burgdorferi sensu stricto
,
Borrelia afzelii
,
Borrelia garinii
, and
Borrelia mayonii
. The novel design of multiplexing peptide antigens onto a scaffold to facilitate expression, correct folding, and orientation of the relevant peptides offers a promising advancement, potentially leading to more accurate and timely LB diagnoses and improving patient outcomes.
An
Acinetobacter baumannii
nasal carriage isolate recovered from an asymptomatic patient in Vietnam is extensively antibiotic resistant and produces a rare K71 type capsule
Authors: Shpirt Anna M. , Harmer Christopher J. , Shashkov Alexander S. , Shneider Mikhail M. , Chizhov Alexander O. , Dmitrenok Andrey S. , Popova Anastasiya V. , Kasimova Anastasiya A. , Perepelov Andrei V. , Knirel Yuriy A. , Hall Ruth M. , Kenyon Johanna J.
Published: October 2024

Acinetobacter baumannii
is a leading cause of multidrug-resistant bacterial infections worldwide, and the capsular polysaccharide (CPS) is a major virulence determinant. A previous study of
A. baumannii
from intubated and asymptomatic patients admitted to the intensive care unit (ICU) at the Hospital for Tropical Diseases in Ho Chi Minh City in Vietnam revealed multiple lineages with diverse antibiotic resistance profiles and CPS biosynthesis loci. Here, we show that 48_n, an asymptomatic nasal carriage isolate belonging to ST142, is extensively antibiotic resistant and carries acquired resistance determinants accounting for the resistance profile. 48_n carries the novel KL71 CPS biosynthesis locus in the chromosome. The structure of the CPS produced by 48_n was established using
1
H and
13
C nuclear magnetic resonance spectroscopy, including two-dimensional
1
Н,
1
Н COSY,
1
Н,
1
Н TOCSY,
1
Н,
1
Н ROESY,
1
Н,
13
C HSQC, and
1
Н,
13
C HMBC experiments, and confirmed by Smith degradation. Consistent with the genetic content of KL71, the K71 CPS was found to be made up of octasaccharide K units containing six
l
-rhamnose residues and one residue each of
N
-acetyl-
d
-glucosamine and
d
-glucuronic acid. K71 CPS was branched and closely related to the K74 CPS produced by BAL_309, an antibiotic susceptible ST142 isolate recovered from an intubated patient in the same ICU 7 years later. K71 and K74 differ only in the linkage between K units, and this is due to the replacement of a single gene at the K locus that codes for the Wzy polymerase.

IMPORTANCE

The majority of
Acinetobacter baumannii
genomes sequenced and analyzed to develop an understanding of extensively drug-resistant (XDR) isolates belong to the globally disseminated CC2 clonal complex. While XDR isolates belonging to rarer lineages are often unexplored, detailed analyses could provide novel insights into the spread of resistance, as well as cell surface features such as the CPS that determine the specificity of non-antibiotic therapeutics required to treat XDR infections that resist antimicrobial chemotherapy. Here, we describe the properties of an XDR asymptomatic nasal carriage isolate recovered in Vietnam that belongs to ST142, a rarely encountered sequence type. We report the resistance profile and correlate this with detected resistance determinants. We also solve the structure of the CPS and reveal its relationship with CPS produced by other
A. baumannii
isolates.
Purine and pyrimidine synthesis differently affect the strength of the inoculum effect for aminoglycoside and β-lactam antibiotics
Authors: Hernandez Daniella M. , Marzouk Melissa , Cole Madeline , Fortoul Marla C. , Reddy Kethireddy Saipranavi , Contractor Rehan , Islam Habibul , Moulder Trent , Kalifa Ariane R. , Marin Meneses Estefania , Barbosa Mendoza Maximiliano , Thomas Ruth , Masud Saad , Pubien Sheena , Milanes Patricia , Diaz-Tang Gabriela , Lopatkin Allison J. , Smith Robert P.
Published: October 2024

The inoculum effect has been observed for nearly all antibiotics and bacterial species. However, explanations accounting for its occurrence and strength are lacking. Previous work found that the relationship between [ATP] and growth rate can account for the strength and occurrence of the inoculum effect for bactericidal antibiotics. However, the molecular pathway(s) underlying this relationship, and therefore determining the inoculum effect, remain undiscovered. Using a combination of flux balance analysis and experimentation, we show that nucleotide synthesis can determine the relationship between [ATP] and growth and thus the strength of inoculum effect in an antibiotic class-dependent manner. If the [ATP]/growth rate is sufficiently high as determined by exogenously supplied nitrogenous bases, the inoculum effect does not occur. This is consistent for both
Escherichia coli
and
Pseudomonas aeruginosa
. Interestingly, and separate from activity through the tricarboxylic acid cycle, we find that transcriptional activity of genes involved in purine and pyrimidine synthesis can predict the strength of the inoculum effect for β-lactam and aminoglycosides antibiotics, respectively. Our work highlights the antibiotic class-specific effect of purine and pyrimidine synthesis on the severity of the inoculum effect, which may pave the way for intervention strategies to reduce the inoculum effect in the clinic.

IMPORTANCE

If a bacterial population can grow and reach a sufficiently high density, routine doses of antibiotics can be ineffective. This phenomenon, called the inoculum effect, has been observed for nearly all antibiotics and bacterial species. It has also been reported to result in antibiotic failure in the clinic. Understanding how to reduce the inoculum effect can make high-density infections easier to treat. Here, we show that purine and pyrimidine synthesis affect the strength of the inoculum effect; as the transcriptional activity of pyrimidine synthesis increases, the strength of the inoculum effect for aminoglycosides decreases. Conversely, as the transcriptional activity of purine synthesis increases, the strength of the inoculum effect for β-lactam antibiotics decreases. Our work highlights the importance of nucleotide synthesis in determining the strength of the inoculum effect, which may lead to the identification of new ways to treat high-density infections in the clinic.
Identification of new SdiA regulon members of
Escherichia coli
,
Enterobacter cloacae
, and
Salmonella enterica
serovars Typhimurium and Typhi
Authors: Schwieters Andrew , Ahmer Brian M. M.
Published: October 2024

Bacteria can coordinate behavior in response to population density through the production, release, and detection of small molecules, a phenomenon known as quorum sensing.
Salmonella enterica
is among a group of Enterobacteriaceae that can detect signaling molecules of the
N
-acyl homoserine lactone (AHL) type but lack the ability to produce them. The AHLs are detected by the LuxR-type transcription factor, SdiA. This enables a behavior known as eavesdropping, where organisms can sense the signaling molecules of other species of bacteria. The role of SdiA remains largely unknown. Here, we use RNA-seq to more completely identify the
sdiA
regulons of two clinically significant serovars of
Salmonella enterica
: Typhimurium and Typhi. We find that their
sdiA
regulons are largely conserved despite the significant differences in pathogenic strategy and host range of these two serovars. Previous studies identified
sdiA
-regulated genes in
Escherichia coli
and
Enterobacter cloacae
, but there is surprisingly no overlap in regulon membership between the different species. This led us to individually test orthologs of each regulon member in the other species and determine that there is indeed some overlap. Unfortunately, the functions of most
sdiA
-regulated genes are unknown, with the overall function of eavesdropping in these organisms remaining unclear.

IMPORTANCE

Many bacterial species detect their own population density through the production, release, and detection of small molecules (quorum sensing).
Salmonella
and other Enterobacteriaceae have a modified system that detects the
N
-acyl-homoserine lactones of other bacteria through the solo quorum sensing receptor SdiA, a behavior known as eavesdropping. The roles of
sdiA
-dependent eavesdropping in the lifecycles of these bacteria are unknown. In this study, we identify
sdiA
-dependent transcriptional responses in two clinically relevant serovars of
Salmonella
, Typhimurium and Typhi, and note that their responses are partially conserved. We also demonstrate for the first time that
sdiA
-dependent regulation of genes is partially conserved in
Enterobacter cloacae
and
Escherichia coli
as well, indicating a degree of commonality in eavesdropping among the Enterobacteriaceae.
Purine limitation prevents the exogenous pyridoxal 5′-phosphate accumulation of
Salmonella enterica yggS
mutants
Authors: Ezekiel Kailey S. , Downs Diana M.
Published: October 2024

YggS belongs to the highly conserved pyridoxal 5′-phosphate (PLP) binding protein family (COG0325) that is found in all domains of life. Though no precise biochemical activity or molecular mechanism has been determined for this protein, an involvement in vitamin B
6
homeostasis has been demonstrated in multiple organisms. In
Salmonella enterica
, loss of YggS results in altered B
6
vitamer pools, including an accumulation of PLP in the growth medium. Transposon mutagenesis identified an insertion upstream of
purC
(encoding 5′-phosphoribosyl-5-aminoimidazole-4-
N
-succinocarboxamide synthetase, EC 6.3.2.6) that eliminated accumulation of PLP in the spent medium. Genetic characterization of the insertion showed the causative effect was reduced expression of
purC
, which limited purine biosynthesis. Data herein shows that purine limitation decreased the exogenous accumulation of B
6
vitamers of a
yggS
mutant but did not suppress other
yggS
mutant phenotypes. Neither limitation for ATP, regulation by PurR, or decreased growth rate, all of which are direct consequences of purine limitation, prevented exogenous B
6
vitamer accumulation of a
yggS
mutant. This work establishes a relationship between the status of purine biosynthesis and the impact of a
yggS
mutation. It lays the foundation for continued efforts to identify the physiological role of YggS and its homologs.

IMPORTANCE

Pyridoxal 5′-phosphate is the active form of vitamin B
6
and is an essential cofactor in all domains of life. PLP can be synthesized
de novo
or salvaged from the environment from one of the six B
6
vitamers. B
6
vitamer levels appear to be tightly regulated, and alterations in their levels can have deleterious effects, most notably being the development of B6-dependent epilepsy in humans. YggS homologs are broadly conserved across multiple organisms and considered to be involved in maintaining B
6
homeostasis, though no specific mechanism has been defined. The current study showed that the exogenous accumulation of PLP caused by a lack of YggS can be prevented by purine limitation. The demonstration that purine limitation impacts exogenous PLP accumulation separates one consequence of a
yggS
mutation for further study and contributes to continuing efforts to define the biochemical and physiological roles of the COG0325 family of proteins.
Optimal 16S rRNA gene amplicon sequencing analysis for oral microbiota to avoid the potential bias introduced by trimming length, primer, and database
Authors: Nagai Takahiko , Shiba Takahiko , Komatsu Keiji , Watanabe Takayasu , Nemoto Takashi , Maekawa Shogo , Kobayashi Ryota , Matsumura Shunsuke , Ohsugi Yujin , Katagiri Sayaka , Takeuchi Yasuo , Iwata Takanori
Published: October 2024

16S rRNA gene amplicon sequencing analysis is used to investigate bacterial communities; however, the estimated bacterial composition can differ from the original due to experimental and analytical biases. Therefore, this study determines the optimal conditions to minimize the potential biases in 16S rRNA gene amplicon sequencing analysis using different DNA samples, trimming lengths, primers, and databases. The results of the mock1 community with 250 and 300 bp paired-end (PE), comprising 15 bacteria from various environments, showed the highest similarity between the theoretical value and the data using the Greengenes2 and the V3 region at the genus level and V5–V6 at the species level. In the 300 bp PE sequencing analysis of the mock2 community, comprising six major oral bacteria, the data using the V3–V4, V4, and V5–V6 regions with the SILVA, Greengenes2, and the Human Oral Microbiome Database (HOMD) showed the highest similarity to the theoretical values at the genus level. At the species level, the data using the V3–V4 and V4 regions with Greengenes2 and the data using the V1–V2 with HOMD exhibited the highest alignment with the theoretical values. In the species analysis of the dental calculus samples with 300 bp PE, the Shannon index value was higher with the V1–V2 region and HOMD than with others. Our results suggest that the optimal conditions for oral microbiome analysis are the combinations of 300 bp PE and the V3–V4 or V4 region with the Greengenes2 and the V1–V2 with HOMD.

IMPORTANCE

The 16S rRNA gene amplicon sequencing analysis is frequently used in oral microbiome research. However, this method can have biases that distort the experimental data, which depend on the methodological steps, including sequencing length, trimming length, selected amplification regions, and referenced databases. In this study, a combination of 300 bp PE and the primer targeting the V3–V4 or V4 regions with the Greengenes2 and the V1–V2 region with the HOMD was the most bias-minimizing condition for oral microbiota analysis. In addition, this is the first report of such analyses in modern Japanese dental calculus. The methods used in this study will aid in setting appropriate conditions for sequence analysis of microbiota obtained not only from the oral cavity but also from any environment.
Twenty year analysis of professional men’s rugby union knee injuries from the English premiership shows high rates and burden
Authors: West Stephen W , Hudson Sam J , Starling Lindsay , Cross Matthew , Williams Sean , McKay Carly D , Cazzola Dario , Brooks John H M , Murray Rory , Williams Andy , Kemp Simon P T , Stokes Keith A
Published: October 2024

Objectives

To determine the rates, severity and burden of knee injuries in professional male rugby union from the English Premiership.

Methods

Injury and exposure data were captured over 20 seasons using a prospective cohort design. Knee injury incidence, days’ absence and burden were recorded for each injury type and by pitch surface type for match and training.

Results

The rate of knee injury in matches was 9.8/1000 hours (95% CIs 9.3–10.3). Mean days lost were 50 (95% CI 46 to 53) in matches and 51 (95% CI 44 to 57) in training. In matches, medial collateral ligament injuries were the most common, while anterior cruciate ligament (ACL) injuries had the highest mean severity and burden. There was no significant change in the count of knee injuries over time; however, average severity increased significantly (annual change: 2.18 days (95% CI 1.60 to 2.77); p<0.001). The incidence of match knee injury was 44% higher on artificial pitches than grass pitches (incidence rate ratio: 1.44 (95% CI 1.21 to 1.69); p<0.01), with no significant difference in severity between surfaces. In matches, the tackle was the event most commonly associated with knee injuries for all diagnoses, except ACL injuries (running). In training, running was a more common injury event than the tackle.

Conclusion

Knee injuries in matches are common and severe in English professional men’s rugby union. Despite an increased focus on player conditioning and injury prevention throughout the study period, rates of knee injury remained stable, and resulting days’ absence increased. New strategies for the prevention of knee injuries should be considered a priority.
Multicentre study to assess the performance of an artificial intelligence instrument to support qualitative diagnosis of colorectal polyps
Authors: Sato Keigo , Kuramochi Mizuki , Tsuchiya Akihiko , Yamaguchi Akihiro , Hosoda Yasuo , Yamaguchi Norio , Nakamura Naohiro , Itoi Yuki , Hashimoto Yu , Kasuga Kengo , Tanaka Hirohito , Kuribayashi Shiko , Takeuchi Yoji , Uraoka Toshio
Published: October 2024

Objective

Computer-aided diagnosis (CAD) using artificial intelligence (AI) is expected to support the characterisation of colorectal lesions, which is clinically relevant for efficient colorectal cancer prevention. We conducted this study to assess the diagnostic performance of commercially available CAD systems.

Methods

This was a multicentre, prospective performance evaluation study. The endoscopist diagnosed polyps using white light imaging, followed by non-magnified blue light imaging (non-mBLI) and mBLI. AI subsequently assessed the lesions using non-mBLI (non-mAI), followed by mBLI (mAI). Eventually, endoscopists made the final diagnosis by integrating the AI diagnosis (AI+endoscopist). The primary endpoint was the accuracy of the AI diagnosis of neoplastic lesions. The diagnostic performance of each modality (sensitivity, specificity and accuracy) and confidence levels were also assessed.

Results

Overall, 380 lesions from 139 patients were included in the analysis. The accuracy of non-mAI was 83%, 95% CI (79% to 87%), which was inferior to that of mBLI (89%, 95% CI (85% to 92%)) and mAI (89%, 95% CI (85% to 92%)). The accuracy (95% CI) of diagnosis by expert endoscopists using mAI (91%, 95% CI (87% to 94%)) was comparable to that of expert endoscopists using mBLI (91%, 95% CI (87% to 94%)) but better than that of non-expert endoscopists using mAI (83%, 95% CI (75% to 90%)). The level of confidence in making a correct diagnosis was increased when using magnification and AI.

Conclusions

The diagnostic performance of mAI for differentiating colonic lesions is comparable to that of endoscopists, regardless of their experience. However, it can be affected by the use of magnification as well as the endoscopists’ level of experience.
Political engagement: a key pillar in revitalisation of polio and routine immunisation programmes in the Democratic Republic of the Congo
Authors: Kamba Roger , El Mourid Amine , Mpoyi Ngambwa Raoul , Chungu Salumu Donat , Le Gargasson Jean-Bernard , Nacoulma Daniel , Nimpa Mengouo Marcellin , Meyer Nolan , Luhata Christophe , Hoff Nicole A , Samaha Hadia , Madika Collard , Mputu Christelle , Tangney Sylvia , Nogier Cyril , Diomi Chris , Merritt Sydney , Din Emma , Kabila Polydor , Burgett Annabelle , Nyombo Didier , Assy Emmanuelle , Nkamba Dalau Mukadi , Bertin Lora , Hatton Trad , Kaba Didine , Rimoin Anne W , Mukamba Musenga Elisabeth , Cikomola Aimé , Mwamba Guillaume Ngoie , Ramazani Sylvain Yuman , Senouci Kamel , Robert Magdalena
Published: October 2024

Immunisation is a high priority for improving health outcomes. Yet, in many low-income and middle-income countries, achieving coverage targets independently is hindered by lack of domestic resources and reliance on partners’ support. Both the 2001 Abuja Declaration and 2016 Addis Declaration were key political commitments to improving immunisation coverage; however, many signatories have yet to meet international targets. Despite signing the Global Vaccine Action Plan and Addis Declaration, the Democratic Republic of the Congo (DRC) was unable to fully disburse its portion of allocated funds to cover vaccines without support from Gavi, the Vaccine Alliance and the World Bank between 2017 and 2019. Additionally, during the same time, vaccine coverage outcomes indicated negative trends, with over 750 000 children considered ‘zero-dose’ in 2018. In 2019, a primary focus of the then newly elected President’s agenda was universal healthcare. In collaboration with development partners and stakeholders, the first Presidential Forum was held as a public commitment to increasing childhood immunisation and ensuring the country remains polio-free. This article seeks to highlight the key outcomes of the Forum such as the signing of the Kinshasa Declaration, which formally set targets and specified national, provincial and community-level commitments to vaccination and polio eradication. As of 2023, three Forums have been conducted to reiterate political commitment to routine immunisation in the DRC. This type of high-level commitment could serve as a template for other countries struggling to have high engagement as targets for polio eradication and strengthened routine immunisation are set for 2025–2030.
Human papillomavirus nonavalent (HPV9) vaccination and risk of immune mediated diseases, myocarditis, pericarditis, and thromboembolic outcomes in Denmark: self-controlled case series study
Authors: Faksová Kristýna , Laksafoss Anna D , Hviid Anders
Published: October 2024

Objective

To assess the associations between vaccination with the nonavalent human papillomavirus (HPV9) vaccine and immune mediated diseases, myocarditis, pericarditis, arterial thromboembolism, and venous thromboembolism with or without thrombocytopenia, in adolescent girls and boys in Denmark.

Design

Self-controlled case series study.

Setting

Population based study of linked nationwide health registers in Denmark for HPV vaccination and hospital diagnosis data, 1 October 2017 (or age 10 years) to 31 December 2022 or censored. Personal data were obtained from the Central Person Register. Information on dates of HPV vaccination and type of vaccine were obtained from the Danish Vaccination Register. Primary or secondary diagnoses of inpatient or outpatient hospital contact were sourced from the Danish National Patient Register.

Participants

Source cohort 854 586. 350 687 individuals aged 10-17 years living in Denmark received at least one dose of HPV9 vaccine. Self-controlled case series analysis of 3354 individuals (1913 girls and 1441 boys) who received at least one dose of HPV9 vaccine and had at least one outcome.

Main outcome measures

Rate ratios of the study outcomes in a 28 day or 180 day risk period (depending on the type of outcome) after HPV9 vaccination compared with the reference period were calculated. 47 immune mediated diseases, myocarditis, pericarditis, and seven thromboembolic outcomes were assessed. A safety signal for a specific outcome was identified if at least three outcomes were seen in the risk period after vaccination, the rate ratio was significantly increased (lower bound of the 95% confidence interval (CI) for the self-controlled case series rate ratio >1.0), and the false discovery rate adjusted P value was significant (<0.05).

Results

696 776 doses of any HPV vaccine were given during the study period, including 673 530 doses of HPV9 vaccine in 350 687 individuals who received at least one dose. In the self-controlled case series analysis, rate ratios of all immune mediated outcomes combined were 0.99 (95% CI 0.86 to 1.13) and 1.03 (0.89 to 1.20) in girls and boys, respectively, after HPV9 vaccination. Rate ratios for any of the 47 analysed immune mediated outcomes were not increased in the risk periods in girls after vaccination. The only increased rate ratio seen was for Raynaud's disease (rate ratio 2.62, 95% CI 1.07 to 6.40) after HPV9 vaccination in boys, which did not fulfil the criteria of a safety signal. These findings should be interpreted in the light of the study limitations. None of the other 55 outcomes examined showed an association with HPV9 vaccination.

Conclusions

The results of this study did not suggest an association between HPV9 vaccination and the study outcomes in adolescent boys and girls aged 10-17 years. This study contributes to the evidence on the safety of the HPV9 vaccine.
Making Every Contact Count: health professionals’ experiences of integrating conversations about Snacktivity to promote physical activity within routine consultations – a qualitative study
Authors: Krouwel Matthew , Greenfield Sheila , Sanders James P , Gokal Kajal , Chalkley Anna , Griffin Ryan A , Parretti Helen , Jolly Kate , Skrybant Magdalena , Biddle Stuart , Greaves Colin , Esliger Dale W , Sherar Lauren B , Edwardson Charlotte , Yates Thomas , Maddison Ralph , Frew Emma , Mutrie Nanette , Ives Natalie , Tearne Sarah , Daley Amanda J
Published: October 2024

Objective

Helping people to change their health behaviours is becoming a greater feature within the role of health professionals, including through whole system initiatives such as Making Every Contact Count. Health services provide an ideal setting to routinely promote health behaviours, including physical activity. Snacktivity is a novel approach that promotes small bouts of physical activity (activity snacks) throughout the day. This study explored health professionals’ initial experiences of delivering a Snacktivity intervention to promote physical activity within routine health consultations. A further aim was to investigate health professionals’ ability/fidelity in delivering the Snacktivity intervention to their patients.

Design

Semistructured interviews (n=11) and audio recording of consultations (n=46).

Setting and participants

Healthcare professionals from a variety of specialisms who delivered the Snacktivity intervention within patient consultations.

Results

Analyses revealed two higher-level themes of interest: (1) health professionals’ conceptualisation of Snacktivity (subthemes: observations/reflections about patients’ understanding, engagement and enthusiasm for delivering the Snacktivity intervention) and (2) health professionals’ understanding of Snacktivity and experience in delivering the intervention (subthemes: delivering Snacktivity; limitations, challenges and possible improvements). Consultation audio recordings demonstrated health professionals delivered the Snacktivity intervention with high levels of fidelity. Health professionals were proficient and supportive of delivering the Snacktivity intervention within consultations although practical barriers to implementation such as time constraints were raised, and confidence in doing so was mixed.

Conclusions

Health professionals were proficient and supportive of delivering the Snacktivity intervention within consultations. The primary barrier to implementation was the time to deliver it, however, gaining greater experience in the intervention and improving behaviour change counselling skills may reduce this barrier.

Trial registration number

ISRCTN64851242.
Assessment of bleeding events in patients receiving DOACs with or without statins to treat venous thromboembolism: insights from the RIETE registry
Authors: Del Giorno Rosaria , Mazzolai Lucia , Keller Sanjiv , Siniscalchi Carmine , Lopez-Jimenez Luciano , Ballaz Aitor , Montenegro Ana Cristina , Otero Remedios , Rashidi Farid , Monreal Manuel
Published: October 2024

Objective

To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).

Design

Observational cohort analysis based on a multicentre international registry.

Setting

Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.

Participants

A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.

Methods

Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.

Results

From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).

Conclusions

In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.
Care gaps among people presenting to the hospital following self-harm: observational study of three emergency departments in England
Authors: Steeg Sarah , Bickley Harriet , Clements Caroline , Quinlivan Leah M , Barlow Steven , Monaghan Elizabeth , Naylor Fiona , Smith Jonathan , Mughal Faraz , Robinson Catherine , Gnani Shamini , Kapur Navneet
Published: October 2024

Objectives

This study aims to examine the proportions of patients referred to mental health, social and voluntary, community and social enterprise (VCSE) services and general practice and to assess care gaps among people presenting to the hospital following self-harm.

Design

Population-based observational study. Data were extracted from hospital records.

Setting

Three emergency departments (EDs) in Manchester, UK.

Participants

26 090 patients aged 15+ years who presented to participating EDs following self-harm and who received a psychosocial assessment by a mental health specialist.

Primary and secondary outcome measures

Primary outcome measures are as follows: care gaps, estimated from the proportion of patients with evidence of social and mental health needs with no new or active referral to mental health, social and VCSE services. Secondary outcome measures are as follows: proportions of referrals by groups of patients, estimated mental health and social needs of patients. Indicators of mental health and social need were developed with academic clinicians (psychiatrist, general practitioner and social worker) and expert lived experience contributors.

Results

96.2% (25 893/26 909) of individuals were estimated as having mental health needs. Among this group, 29.9% (6503/21 719) had no new or active referral to mental health services (indicating a care gap). Mental healthcare gaps were greater in men and those who were aged under 35 years, from a black, South Asian or Chinese ethnic group, living in the most deprived areas and had no mental health diagnosis, or alcohol, substance misuse, anxiety or trauma-related disorder. 52.8% (14 219/26 909) had social needs, with care gaps greater for men, individuals aged 45–64 and those who were unemployed or had a diagnosed mental disorder.

Conclusions

Care gaps were higher among hospital-presenting groups known to have increased risks of suicide: men, those in middle age, unemployed individuals and those misusing substances. Improved access to mental health, social and VCSE services and general practice care is vital to reduce inequities in access to self-harm aftercare.
Effectiveness of psychological interventions for carers of patients with severe mental illness (SMI): a systematic review
Authors: Ali Syed , Tallent Jacqueline , Sambrook Harry , MacInnes Douglas , Kinane Catherine
Published: October 2024

Objectives

Interventions for carers of patients with severe mental illness (SMI) are effective in improving patient outcomes. This review examined the effectiveness of psychological interventions or support designed to help carers of patients with SMI.

Design

A systematic review of randomised controlled trials (RCTs) was conducted. Study selection, data abstraction and risk of bias assessments were independently conducted and duplicated. The reporting of this review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

Data sources

CINAHL, CENTRAL, EMBASE, Medline and PsycINFO were searched from inception to 30 April 2024.

Eligibility criteria

Only studies using an RCT were considered. All other research designs were excluded. The included population was carers over 18 caring for a patient with SMI. Any psychological, psychosocial or psychoeducational interventions were included. Patients under 18, diagnosed with dementia or learning disabilities comorbidity, were excluded.

Data extraction and synthesis

Study characteristics and outcome data (mean and SD) for each included study were collected. Review Manager (RevMan) was used to manage the data. Meta-analysis was not considered appropriate due to the heterogeneity of the included studies. The results were presented as a narrative synthesis.

Results

This review included 3869 participants from 32 RCTs and demonstrated a beneficial effect of psychological interventions for carers. Psychoeducation was widely used and the most evaluated intervention for carers.

Conclusions

Psychological interventions for carers are beneficial in helping to reduce negative outcomes and enhance positive outcomes. Future research could focus on exploring the impact of interventions on less evaluated outcomes such as depressive and anxiety symptoms.

PROSPERO registration number

CRD42021233181.
Level of option B+PMTCT drug adherence with male partner involvement and associated factors among breastfeeding women until 18 months in North Gojjam Zone, Amhara region, Northwest Ethiopia, 2022: a multicentre cross-sectional study
Authors: Belachew Tegegne Wale , Mitiku Assefa Kebie , Tegegne Dagnaw Mersha , Yimer Tigist Seid , Mekuriaw Begizew Yimenu , Mengistu Temesgen Dessie , Aynekulu Getahun Tadele , Ferede Wassie Yazie
Published: October 2024

Background

Adherence to option B+antiretroviral therapy medication is crucial for the effective implementation of the Prevention of Mother-to-Child Transmission (PMTCT) programme. Ethiopia has adopted the WHO’s target of achieving over 95% adherence. However, research conducted in southern Ethiopia found that only 81.4% of women adhered to option B+medication, which reflects a poor level of adherence and remains a concern.

Objective

The objective of the study was to assess the level of option B+PMTCT drug adherence and associated factors among women who were breast feeding for up to 18 months in government health facilities of North Gojjam Zone, Amhara region, Northwest Ethiopia, 2022

Design

An institution-based cross-sectional study was conducted.

Setting

The study was carried out in hospitals located in the North Gojjam Zone of Northwest Ethiopia.

Participants

The study was conducted with 223 HIV-positive women who were breast feeding for up to 18 months, from 1 March 2022 to 30 April 2022.

Primary and secondary outcomes

The primary outcome was to assess the level of option B+PMTCT drug adherence, while the secondary outcome was to identify factors associated with option B+PMTCT drug adherence among HIV-positive women who were breast feeding for up to 18 months. Associations between variables were analysed using both bivariate and multivariable logistic regression models, with a p<0.05 considered statistically significant at the 95% confidence level.

Results

A total of 223 participants were included, yielding a response rate of 97.8%. The adherence to option B+PMTCT drugs was 62.8%. The type of health facility (adjusted OR, AOR=0.17 (95% CI: 0.008 to 0.35)), partner support involvement (AOR=3.03 (95% CI: 1.12 to 9.13)) and the time taken to reach the facility from home (AOR=6.34 (95% CI: 2.92 to 13.75)) were significantly associated with the level of option B+PMTCT drug adherence.

Conclusion

Option B+PMTCT drug adherence was lower than the recommended level. The type of health facility, partner support and the time required to travel from home to the facility were factors associated with adherence to option B+PMTCT medication. Support from a partner is crucial for improving adherence to option B+medication.
Impact of urban greening on population health in sub-Saharan Africa: a scoping review protocol
Authors: Ansah Edward Wilson , Antiri Ebenezer Oduro , Awuah Hilary Konadu , Salu Promise , Adoripore John , Boakye Anthony Edward
Published: October 2024

Introduction

The rate of urbanisation in sub-Saharan Africa (SSA) has increased remarkably, with the urban population expected to double by 2050. This rapid urbanisation, industrialisation and climate change pose serious public health challenges resulting from increased heat waves and other environmental changes. Urban greening holds promise as a climate change mitigation and adaptation strategy, leading to biodiversity conservation and enhancing the physical, mental and social well-being of the population.

Methods and analysis

This scoping review aims to identify and synthesise studies that investigated the availability and utilisation of green spaces, the factors that affect the utilisation of green spaces as well as the health impacts of urban greening in SSA. A systematic search will be conducted across multiple databases (MEDLINE, PubMed, JSTOR, SCOPUS and Green FILE) and grey literature sources for papers published up to 2024, in line with established scoping review frameworks. The data will be charted and extracted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Extension for Scoping Reviews. We will further synthesise and use thematic analysis to fully understand the relationship between urban greening and population health in SSA.

Ethics and dissemination

Ethical approval will not be required because primary data will not be collected for the study. The results of this study come from published articles, which are publicly available. The results of the review will be submitted to a peer-reviewed journal for publication and presented at workshops and conferences.

Registration

The scoping review protocol has been registered on the Open Science Frameworkhttps://osf.io/nfh68.
Virtual reality-guided mindfulness intervention to enhance psychosocial well-being in caregivers of end-stage kidney disease patients: protocol for a mixed-methods pilot randomised controlled trial
Authors: Shankar Ravi , Hong Wei Zhen , Bundele Anjali , Si Koh Pei , Mukhopadhyay Amartya
Published: October 2024

Introduction

Caregivers of patients with end-stage kidney disease (ESKD) face significant challenges that contribute to caregiver burden, negatively impacting their psychosocial well-being. Virtual-reality (VR)-guided mindfulness interventions have shown promise in reducing stress, anxiety and depression in various populations.

Methods and analysis

This pilot study aims to evaluate the efficacy and feasibility of a VR-guided mindfulness intervention for ESKD caregivers. A single-centre, single-blind, parallel-group pilot randomised controlled trial will be conducted. Thirty ESKD caregivers will be randomly allocated to either the VR-guided mindfulness intervention group or the sham VR control group. The intervention group will receive a 6 week home-based VR-guided mindfulness programme, while the control group will view relaxing nature videos without mindfulness content. Participants will be assessed at baseline, post-intervention (6 weeks) and follow-up (12 weeks) using validated questionnaires for caregiver burden (Zarit Burden Interview (ZBI)), stress, anxiety, depression (Depression Anxiety Stress Scale-21 (DASS-21)), quality of life (36-Item Short Form Health Survey (SF-36)) and mindfulness (Five Facet Mindfulness Questionnaire (FFMQ)). Feasibility outcomes include accrual rates, retention, adherence, questionnaire completion and side effect rates. Semi-structured interviews will explore participants’ experiences with the intervention.

Ethics and dissemination

The study has been approved by the NHG Domain Specific Review Board (Reference: 2024–3940-APP1). The results of this pilot study will be reported in peer-reviewed open-access journals and shared with participants and stakeholders.

Trial registration

NCT06479200.
Ventilator performances for non-invasive ventilation: a bench study
Authors: Caillard Christian , Fresnel Emeline , Artaud-Macari Elise , Cuvelier Antoine , Tamion Fabienne , Patout Maxime , Girault Christophe
Published: October 2024

Introduction

A wide range of recent ventilators, dedicated or not, is available for non-invasive ventilation (NIV) in respiratory or intensive care units (ICU). We conducted a bench study to compare their technical performances.

Methods

Ventilators, including five ICU ventilators with NIV mode on, two dedicated NIV ventilators and one transport ventilator, were evaluated on a test bench for NIV, consisting of a 3D manikin head connected to an ASL 5000 lung model via a non-vented mask. Ventilators were tested according to three simulated lung profiles (normal, obstructive, restrictive), three levels of simulated air leakage (0, 15, 30 L/min), two levels of pressure support (8, 14 cmH2O) and two respiratory rates (15, 25 cycles/min).

Results

The global median Asynchrony Index (AI) was higher with ICU ventilators than with dedicated NIV ventilators (4% (0; 76) vs 0% (0; 15), respectively; p<0.05) and different between all ventilators (p<0.001). The AI was higher with ICU ventilators for the normal and restrictive profiles (p<0.01) and not different between ventilators for the obstructive profile. Auto-triggering represented 43% of all patient-ventilator asynchrony. Triggering delay, cycling delay, inspiratory pressure-time product, pressure rise time and pressure at mask were different between all ventilators (p<0.01). Dedicated NIV ventilators induced a lower pressure-time product than ICU and transport ventilators (p<0.01). There was no difference between ventilators for minute ventilation and peak flow.

Conclusion

Despite the integration of NIV algorithms, most recent ICU ventilators appear to be less efficient than dedicated NIV ventilators. Technical performances could change, however, according to the underlying respiratory disease and the level of air leakage.