bluuebunny/crossref_metadata_2025 huggingface dataset:
A Survey of Current Exercise and Nutritional Strategies for Management of Dysmenorrhea
Authors: Hirsch Katie R. , VanDusseldorp Trisha A. , Karns Hailey E. , Persaud Katelynn T. , Ramey Kaitlyn T. , Saenz Catherine
Published: August 2024

This study characterized exercise and nutritional strategies being used by women to manage dysmenorrhea. Women with self-reported menstrual pain (N = 182; age, 31.7 ± 8.9 years; 73% premenopausal; 44% contraceptive users; 66% White; 70% non-Hispanic) completed a web-based survey about the presence and severity of menstrual pain, pain management strategies (exercise, medications, nutrition, others), and perceived challenges to using nutrition for pain management. Menstrual pain was reported to be greatest on Day 1 of menstruation (mean: 6.6/10) and was “sometimes” (36%) or “often” (31%) disruptive to exercise. For exercise as a strategy to manage pain, 31% reported improvements, 23% reported no change, and 11% reported worsening of pain. A majority of women reported using nonsteroidal anti-inflammatory drugs (71%) or other medications to manage pain (sometimes, 25%; often, 21%; always, 25%). Almost half of women (47%) reported using some other method to manage pain (sometimes, 22%; often, 15%; always, 10%), most often heat. Less women (18%) reported using dietary or herbal supplements (sometimes, 7%; often, 7%; always, 4%) or dietary changes (sometimes, 7%; often, 5%; always, 5%). The most common reasons for not using nutrition to manage menstrual pain included not knowing what to buy or what to try, had never tried, and being unsure about supplements. The level of pain women experience with dysmenorrhea is significant and disruptive to exercise participation. However, few women report using nutritional strategies due to being unsure of what to buy or try. Quality studies targeting nutritional menstrual pain management strategies are needed.
Efficacy of aspergillomarasmine A/meropenem combinations with and without avibactam against bacterial strains producing multiple β-lactamases
Authors: Rotondo Caitlyn M. , Wright Gerard D.
Published: August 2024

The effectiveness of β-lactam antibiotics is increasingly threatened by resistant bacteria that harbor hydrolytic β-lactamase enzymes. Depending on the class of β-lactamase present, β-lactam hydrolysis can occur through one of two general molecular mechanisms. Metallo-β-lactamases (MBLs) require active site Zn
2+
ions, whereas serine-β-lactamases (SBLs) deploy a catalytic serine residue. The result in both cases is drug inactivation via the opening of the β-lactam warhead of the antibiotic. MBLs confer resistance to most β-lactams and are non-susceptible to SBL inhibitors, including recently approved diazabicyclooctanes, such as avibactam; consequently, these enzymes represent a growing threat to public health. Aspergillomarasmine A (AMA), a fungal natural product, can rescue the activity of the β-lactam antibiotic meropenem against MBL-expressing bacterial strains. However, the effectiveness of this β-lactam/β-lactamase inhibitor combination against bacteria producing multiple β-lactamases remains unknown. We systematically investigated the efficacy of AMA/meropenem combination therapy with and without avibactam against 10
Escherichia coli
and 10
Klebsiella pneumoniae
laboratory strains tandemly expressing single MBL and SBL enzymes. Cell-based assays demonstrated that laboratory strains producing NDM-1 and KPC-2 carbapenemases were resistant to the AMA/meropenem combination but became drug-susceptible upon adding avibactam. We also probed these combinations against 30 clinical isolates expressing multiple β-lactamases.
E. coli
,
Enterobacter cloacae,
and
K. pneumoniae
clinical isolates were more susceptible to AMA, avibactam, and meropenem than
Pseudomonas aeruginosa
and
Acinetobacter baumannii
isolates. Overall, the results demonstrate that a triple combination of AMA/avibactam/meropenem has potential for empirical treatment of infections caused by multiple β-lactamase-producing bacteria, especially Enterobacterales.
Enhanced accumulation of γ-aminobutyric acid by deletion of aminotransferase genes involved in γ-aminobutyric acid catabolism in engineered
Halomonas elongata
Authors: Zou Ziyan , Kaothien-Nakayama Pulla , Nakayama Hideki
Published: August 2024

Halomonas elongata
OUT30018 is a moderately halophilic bacterium that synthesizes and accumulates ectoine as an osmolyte by activities of the enzymes encoded by the high salinity-inducible
ectABC
operon. Previously, we engineered a γ-aminobutyric acid (GABA)-producing
H. elongata
GOP-Gad (Δ
ectABC::mCherry-HopGadmut
) from an ectoine-deficient mutant of this strain due to its ability to use high-salinity biomass waste as substrate. Here, to further increase GABA accumulation, we deleted
gabT,
which encodes GABA aminotransferase (GABA-AT) that catalyzes the first step of the GABA catabolic pathway, from the
H. elongata
GOP-Gad genome. The resulting strain
H. elongata
ZN3 (Δ
ectABC::mCherry-HopGadmut
Δ
gabT
) accumulated 291 µmol/g cell dry weight (CDW) of GABA in the cells, which is a 1.5-fold increase from
H. elongata
GOP-Gad’s 190 µmol/g CDW. This result has confirmed the role of GABA-AT in the GABA catabolic pathway. However, redundancy in endogenous GABA-AT activity was detected in a growth test, where a
gabT
-deletion mutant of
H. elongata
OUT30018 was cultured in a medium containing GABA as the sole carbon and nitrogen sources. Because L-2,4-diaminobutyric acid aminotransferase (DABA-AT), encoded by an
ectB
gene of the
ectABC
operon, shares sequence similarity with GABA-AT, a complementation analysis of the
gabT
and the
ectB
genes was performed in the
H. elongata
ZN3 genetic background to test the involvement of DABA-AT in the redundancy of GABA-AT activity. Our results indicate that the expression of DABA-AT can restore GABA-AT activity in
H. elongata
ZN3 and establish DABA-AT’s aminotransferase activity toward GABA
in vivo
.

IMPORTANCE

In this study, we were able to increase the yield of GABA by 1.5 times in the GABA-producing
H. elongata
ZN3 strain by deleting the
gabT
gene, which encodes GABA-AT, the initial enzyme of the GABA catabolic pathway. We also report the first
in vivo
evidence for GABA aminotransferase activity of an
ectB
-encoded DABA-AT, confirming a longstanding speculation based on the reported
in vitro
GABA-AT activity of DABA-AT. According to our findings, the DABA-AT enzyme can catalyze the initial step of GABA catabolism, in addition to its known function in ectoine biosynthesis. This creates a cycle that promotes adequate substrate flow between the two pathways, particularly during the early stages of high-salinity stress response when the expression of the
ectB
gene is upregulated.
A promoter–RBS library for fine-tuning gene expression in
Methanosarcina acetivorans
Authors: Zhu Ping , Molina Resendiz Mariana , von Ossowski Ingemar , Scheller Silvan
Published: August 2024

Methanogens are the main biological producers of methane on Earth.
Methanosarcina acetivorans
is one of the best characterized methanogens that has powerful genetic tools for genome editing. To study the physiology of this methanogen in further detail as well as to effectively balance the flux of their engineered metabolic pathways in expansive project undertakings, there is the need for controlled gene expression, which then requires the availability of well-characterized promoters and ribosome-binding sites (RBS). In this study, we constructed a library of 33 promoter–RBS combinations that includes 13 wild-type and 14 hybrid combinations, as well as six combination variants in which the 5'-untranslated region (5'UTR) was rationally engineered. The expression strength for each combination was calculated by inducing the expression of the β-glucuronidase reporter gene in
M. acetivorans
cells in the presence of the two most used growth substrates, either methanol (MeOH) or trimethyl amine (TMA). In this study, the constructed library covers a relatively wide range (140-fold) between the weakest and strongest promoter–RBS combination as well as shows a steady increase and allows different levels of gene expression. Effects on the gene expression strength were also assessed by making measurements at three distinct growth phases for all 33 promoter–RBS combinations. Our promoter–RBS library is effective in enabling the fine-tuning of gene expression in
M. acetivorans
for physiological studies and the design of metabolic engineering projects that, e.g., aim for the biotechnological valorization of one-carbon compounds.

IMPORTANCE

Methanogenic archaea are potent producers of the greenhouse gas methane and thus contribute substantially to global warming. Under controlled conditions, these microbes can catalyze the production of biogas, which is a renewable fuel, and might help counter global warming and its effects. Engineering the primary metabolism of
Methanosarcina acetivorans
to render it better and more useful requires controllable gene expression, yet only a few well-characterized promoters and RBSs are presently available. Our study rectifies this situation by providing a library of 33 different promoter–RBS combinations with a 140-fold dynamic range in expression strength. Future metabolic engineering projects can take advantage of this library by using these promoter–RBS combinations as an efficient and tunable gene expression system for
M. acetivorans
. Furthermore, the methodologies we developed in this study could also be utilized to construct promoter libraries for other types of methanogens.
Exploring strain-level diversity in the gut microbiome through mucin particle adhesion
Authors: Nishiyama Keita , Murakami Ryuta , Nakahata Masaki , Zhou Binghui , Hashikura Nanami , Kaneko Hiroki , Namai Fu , Ikeda-Ohtsubo Wakako , Xiao Jin-Zhong , Kitazawa Haruki , Odamaki Toshitaka
Published: August 2024

Mucin glycoproteins are a significant source of carbon for the gut bacteria. Various gut microbial species possess diverse hydrolytic enzymes and catabolic pathways for breaking down mucin glycans, resulting in competition for the limited nutrients within the gut environment. Adherence to mucin glycans represents a crucial strategy used by gut microbes to access nutrient reservoirs. Understanding these properties is pivotal for comprehending the survival mechanisms of bacteria in the gastrointestinal tract. However, characterization of individual strains within the vast array of coexisting bacteria in the microbiome is challenging. To investigate this, we developed mucin-immobilized particles by immobilizing porcine gastric mucin (PGM) onto glass beads chemically modified with boronic acid. These PGM-immobilized particles were then anaerobically cultured with human fecal microbiota, and the bacteria adhering to PGM were isolated. Interestingly, the microbiome composition remained largely unchanged irrespective of PGM immobilization. Nonetheless, bacteria isolated from PGM-immobilized glass particles exhibited notably higher
N
-acetylgalactosaminidase activity compared to the control beads. Furthermore,
Bacteroides
strains isolated from PGM-immobilized glass particles displayed enhanced adhesive and metabolic properties to PGM. These findings underscore the utility of PGM particles in enriching and isolating specific microbes. Moreover, they highlight substantial differences in microbial properties at the strain level. We anticipate that PGM-immobilized particles will advance culture-based microbiome research, emphasizing the significance of strain-level characterization.

IMPORTANCE

Metabolism of mucin glycans by gut bacteria represents a crucial strategy for accessing nutrient reservoirs. The efficacy of mucin glycan utilization among gut bacteria hinges on the metabolic capabilities of individual strains, necessitating meticulous strain-level characterization. In this investigation, we used glass beads chemically immobilized with mucins to selectively enrich bacteria from fecal fermentation cultures, based on their superior adhesion to and metabolism of mucin glycoproteins. These findings lend support to the hypothesis that the physical interactions between bacteria and mucin glycoprotein components directly correlate with their capacity to utilize mucins as nutrient sources. Furthermore, our study implies that physical proximity may significantly influence bacterial nutrient acquisition within the ecosystem, facilitating gut bacteria’s access to carbohydrate components.
Mycoplasma hyopneumoniae
inhibits the unfolded protein response to prevent host macrophage apoptosis and M2 polarization
Authors: Liu Tong , Zhang Yujuan , Zhao Huanjun , Wu Qi , Xin Jiuqing , Pan Qiao
Published: August 2024

Enzootic pneumonia caused by
Mycoplasma hyopneumoniae
(
M. hyopneumoniae
) has inflicted substantial economic losses on the global pig industry. The progression of
M. hyopneumoniae
induced-pneumonia is associated with lung immune cell infiltration and extensive proinflammatory cytokine secretion. Our previous study established that
M. hyopneumoniae
disrupts the host unfolded protein response (UPR), a process vital for the survival and immune function of macrophages. In this study, we demonstrated that
M. hyopneumoniae
targets the UPR- and caspase-12-mediated endoplasmic reticulum (ER)-associated classical intrinsic apoptotic pathway to interfere with host cell apoptosis signaling, thereby preserving the survival of host tracheal epithelial cells (PTECs) and alveolar macrophages (PAMs) during the early stages of infection. Even in the presence of apoptosis inducers, host cells infected with
M. hyopneumoniae
exhibited an anti-apoptotic potential. Further analyses revealed that
M. hyopneumoniae
suppresses the three UPR branches and their induced apoptosis. Interestingly, while UPR activation typically drives host macrophages toward an M2 polarization phenotype,
M. hyopneumoniae
specifically obstructs this process to maintain a proinflammatory phenotype in the host macrophages. Overall, our findings propose that
M. hyopneumoniae
inhibits the host UPR to sustain macrophage survival and a proinflammatory phenotype, which may be implicated in its pathogenesis in inducing host pneumonia.
The host GTPase Dynamin 2 modulates apical junction structure to control cell-to-cell spread of
Listeria monocytogenes
Authors: Tijoriwalla Serena , Liyanage Thiloma , Herath Thilina U. B. , Lee Nicole , Rehman Attika , Gianfelice Antonella , Ireton Keith
Published: August 2024

The food-borne pathogen
Listeria monocytogenes
uses actin-based motility to generate plasma membrane protrusions that mediate the spread of bacteria between host cells. In polarized epithelial cells, efficient protrusion formation by
L. monocytogenes
requires the secreted bacterial protein InlC, which binds to a carboxyl-terminal Src homology 3 (SH3) domain in the human scaffolding protein Tuba. This interaction antagonizes Tuba, thereby diminishing cortical tension at the apical junctional complex and enhancing
L. monocytogenes
protrusion formation and spread. Tuba contains five SH3 domains apart from the domain that interacts with InlC. Here, we show that human GTPase Dynamin 2 associates with two SH3 domains in the amino-terminus of Tuba and acts together with this scaffolding protein to control the spread of
L. monocytogenes
. Genetic or pharmacological inhibition of Dynamin 2 or knockdown of Tuba each restored normal protrusion formation and spread to a bacterial strain deleted for the
inlC
gene (∆
inlC
). Dynamin 2 localized to apical junctions in uninfected human cells and protrusions in cells infected with
L. monocytogenes
. Localization of Dynamin 2 to junctions and protrusions depended on Tuba. Knockdown of Dynamin 2 or Tuba diminished junctional linearity, indicating a role for these proteins in controlling cortical tension. Infection with
L. monocytogenes
induced InlC-dependent displacement of Dynamin 2 from junctions, suggesting a possible mechanism of antagonism of this GTPase. Collectively, our results show that Dynamin 2 cooperates with Tuba to promote intercellular tension that restricts the spread of ∆
inlC Listeria
. By expressing InlC, wild-type
L. monocytogenes
overcomes this restriction.
The impact of butyrate on group B
Streptococcus
-induced intestinal barrier disruption
Authors: Dominguez Kristen , Pearah Alexia N. , Lindon April K. , Worthington Leigh-Anne M. , Carter Rico R. , John-Lewis Edwards Nichol , Ho Thao T. B. , Darch Sophie E. , Randis Tara M.
Published: August 2024

Group B Streptococcus (
Streptococcus agalactiae
; GBS) is a leading cause of neonatal sepsis worldwide. As a pathobiont of the intestinal tract, it is capable of translocating across barriers leading to invasive disease. Neonatal susceptibility to invasive disease stems from immature intestinal barriers. GBS intestinal colonization induces major transcriptomic changes in the intestinal epithelium related to barrier function. Butyrate, a microbial metabolite produced by fermentation of dietary fiber, bolsters intestinal barrier function against enteric pathogens, and these effects can be transferred
in utero
via the placenta to the developing fetus. Our aim was to determine if butyrate mitigates GBS disruption of intestinal barriers. We used human intestinal epithelial cell (IEC) lines to evaluate the impact of butyrate on GBS-induced cell death and GBS adhesion and invasion. IECs and human fetal tissue-derived enteroids were used to evaluate monolayer permeability. We evaluated the impact of maternal butyrate treatment (mButyrate) using our established mouse model of neonatal GBS intestinal colonization and late-onset sepsis. We found that butyrate reduces GBS-induced cell death, GBS invasion, monolayer permeability, and translocation
in vitro
. In mice, mButyrate decreases GBS intestinal burden in offspring. Our results demonstrate the importance of bacterial metabolites, such as butyrate, in their potential to bolster epithelial barrier function and mitigate neonatal sepsis risk.

IMPORTANCE

Group B
Streptococcus
(GBS) is a leading cause of neonatal morbidity and mortality. It is a commensal of the intestines that can translocate across barriers leading to sepsis in vulnerable newborns. With the rise in antibiotic-resistant strains and no licensed vaccine, there is an urgent need for preventative strategies. Butyrate, a short-chain fatty acid metabolized in the gut, enhances barrier function against pathogens. Importantly, butyrate is transferred
in utero
, conferring these benefits to infants. Here, we demonstrate that butyrate reduces GBS colonization and epithelial invasion. These effects were not microbiome-driven, suggesting butyrate directly impacts epithelial barrier function. Our results highlight the potential impact of maternal dietary metabolites, like butyrate, as a strategy to mitigate neonatal sepsis risk.
The microbiome-derived antibacterial lugdunin acts as a cation ionophore in synergy with host peptides
Authors: Berscheid Anne , Straetener Jan , Schilling Nadine A. , Ruppelt Dominik , Konnerth Martin C. , Schittek Birgit , Krismer Bernhard , Peschel Andreas , Steinem Claudia , Grond Stephanie , Brötz-Oesterhelt Heike
Published: August 2024

Lugdunin is a microbiome-derived antibacterial agent with good activity against Gram-positive pathogens
in vitro
and in animal models of nose colonization and skin infection. We have previously shown that lugdunin depletes bacterial energy resources by dissipating the membrane potential of
Staphylococcus aureus
. Here, we explored the mechanism of action of lugdunin in more detail and show that lugdunin quickly depolarizes cytoplasmic membranes of different bacterial species and acidifies the cytoplasm of
S. aureus
within minutes due to protonophore activity. Varying the salt species and concentrations in buffers revealed that not only protons are transported, and we demonstrate the binding of the monovalent cations K
+
, Na
+
, and Li
+
to lugdunin. By comparing known ionophores with various ion transport mechanisms, we conclude that the ion selectivity of lugdunin largely resembles that of 15-mer linear peptide gramicidin A. Direct interference with the main bacterial metabolic pathways including DNA, RNA, protein, and cell wall biosyntheses can be excluded. The previously observed synergism of lugdunin with dermcidin-derived peptides such as DCD-1 in killing
S. aureus
is mechanistically based on potentiated membrane depolarization. We also found that lugdunin was active against certain eukaryotic cells, however strongly depending on the cell line and growth conditions. While adherent lung epithelial cell lines were almost unaffected, more sensitive cells showed dissipation of the mitochondrial membrane potential. Lugdunin seems specifically adapted to its natural environment in the respiratory tract. The ionophore mechanism is refractory to resistance development and benefits from synergy with host-derived antimicrobial peptides.

IMPORTANCE

The vast majority of antimicrobial peptides produced by members of the microbiome target the bacterial cell envelope by many different mechanisms. These compounds and their producers have evolved side-by-side with their host and were constantly challenged by the host’s immune system. These molecules are optimized to be well tolerated at their physiological site of production, and their modes of action have proven efficient
in vivo
. Imbalancing the cellular ion homeostasis is a prominent mechanism among antibacterial natural products. For instance, over 120 naturally occurring polyether ionophores are known to date, and antimicrobial peptides with ionophore activity have also been detected in microbiomes. In this study, we elucidated the mechanism underlying the membrane potential-dissipating activity of the thiazolidine‐containing cycloheptapeptide lugdunin, the first member of the fibupeptides discovered in a commensal bacterium from the human nose, which is a promising future probiotic candidate that is not prone to resistance development.
Lung abscess following a foreign body extraction
Authors: Hernandez-Rodriguez Maran Y , Goodwin Jessica , Yousef Shatha , ElMallah Mai
Published: August 2024

Lung abscesses are uncommon in the paediatric population, often manifesting with cough, shortness of breath, chest pain and fever. A high index of suspicion is imperative to prevent delays in treatment. This is a case report of a previously healthy child in early childhood with a 5-month history of recurrent left upper lobe (LUL) pneumonia. A foreign body was identified in the LUL and removed via flexible bronchoscopy. Following the foreign body removal, the patient developed a 9 cm lung abscess. A high index of suspicion for a lung abscess post-foreign body removal is important for early diagnosis and ensuring appropriate antibiotic coverage in patients with persistent fever. Intravenous antibiotics are essential in the management of lung abscesses. Consideration should be given to percutaneous drainage in situations where there is minimal improvement after 72 hours of suitable antimicrobial therapy or when the abscess exceeds 6 cm in size.
Age and sex specific thresholds for risk stratification of cardiovascular disease and clinical decision making: prospective open cohort study
Authors: Xu Zhe , Usher-Smith Juliet , Pennells Lisa , Chung Ryan , Arnold Matthew , Kim Lois , Kaptoge Stephen , Sperrin Matthew , Di Angelantonio Emanuele , Wood Angela M
Published: August 2024

Objective

To quantify the potential advantages of using 10 year risk prediction models for cardiovascular disease, in combination with risk thresholds specific to both age and sex, to identify individuals at high risk of cardiovascular disease for allocation of statin treatment.

Design

Prospective open cohort study.

Setting

Primary care data from the UK Clinical Practice Research Datalink GOLD, linked with hospital admissions from Hospital Episode Statistics and national mortality records from the Office for National Statistics in England, 1 January 2006 to 31 May 2019.

Participants

1 046 736 individuals (aged 40-85 years) with no cardiovascular disease, diabetes, or a history of statin treatment at baseline using data from electronic health records.

Main outcome measures

10 year risk of cardiovascular disease, calculated with version 2 of the QRISK cardiovascular disease risk algorithm (QRISK2), with two main strategies to identify individuals at high risk: in strategy A, estimated risk was a fixed cut-off value of ≥10% (ie, as per the UK National Institute for Health and Care Excellence guidelines); in strategy B, estimated risk was ≥10% or ≥90th centile of age and sex specific risk distributions.

Results

Compared with strategy A, strategy B stratified 20 241 (149.8%) more women aged ≤53 years and 9832 (150.2%) more men aged ≤47 years as having a high risk of cardiovascular disease; for all other ages the strategies were the same. Assuming that treatment with statins would be initiated in those identified as high risk, differences in the estimated gain in cardiovascular disease-free life years from statin treatment for strategy B versus strategy A were 0.14 and 0.16 years for women and men aged 40 years, respectively; among individuals aged 40-49 years, the numbers needed to treat to prevent one cardiovascular disease event for strategy B versus strategy A were 39 versus 21 in women and 19 versus 15 in men, respectively.

Conclusions

This study quantified the potential gains in cardiovascular disease-free life years when implementing prevention strategies based on age and sex specific risk thresholds instead of a fixed risk threshold for allocation of statin treatment. Such gains should be weighed against the costs of treating more younger people with statins for longer.
Under-representation of older Indian persons with cancer in clinical trials
Authors: Noronha Vanita , Patil Vijay , Menon Nandini , Kolkur Manali , Peelay Zoya , Shah Minit , Mathrudev Vijayalakshmi , Shah Srushti , Nawale Kavita , Nair Nita S , Ramaswamy Anant , Ostwal Vikas , Ghosh-Laskar Sarbani , Agarwal Jai Prakash , Chaturvedi Pankaj , Chopra Supriya , Murthy Vedang , Myatra Sheila N , Divatia Jigeeshu , Gota Vikram , Gupta Sudeep , Chaudhari Vikram , Jiwnani Sabita , Shrikhande Shailesh V , Vaish Richa , Chaukar Devendra , Thiagarajan Shivakumar , Nair Sudhir , D'Cruz Anil , Oak Amey , Hawaladar Rohini , Roy Chowdhury Oindrila , Banavali Shripad , Badwe Rajendra , Prabhash Kumar
Published: August 2024

Objective

Older patients with cancer have traditionally been under-represented in global clinical trials. There are no data from India regarding this issue.

Methods and analysis

This was a retrospective analysis done at our institute on interventional studies conducted between 2003 and 2023 in adult patients with malignancies. We excluded studies done exclusively in the paediatric population and observational studies.

Results

We included 21 894 patients enrolled in 150 interventional trials from the departments of surgical, medical, and radiation oncology, anaesthesia, and clinical pharmacology; 110 (73.3%) were investigator initiated. There were 38 trials (25.3%) in breast cancer (6141 patients, 28%), and 33 (22%) in head and neck cancer (6975 patients, 31.9%). Studies were predominantly phase III (97 trials (64.7%)). Multicentric studies comprised approximately one-third (48, 32%). The median age of enrolled patients was 51 years (IQR 43–59). There were 5132 (23.4%) participants aged ≥60 years, 2678 (12.2%) ≥65 years and 1045 (4.8%) ≥70 years. Data from the hospital registry revealed that 30% of adult registrations were ≥60 years. There was a significant increase in the proportion of older patients enrolled in clinical trials from 2003 (8%) to 2019 (22%) compared with their proportion in the hospital registry (stable at 28%–29%); p<0.001.

Conclusion

There is a gap between the proportion of older Indian adults with cancer in the hospital registry and those enrolled in interventional clinical trials, however, this gap has shrunk over time. Various factors that limit the recruitment of this vulnerable cohort like age-specific eligibility criteria are immediately actionable to make clinical trials more inclusive.
Elucidating the dynamics and impact of the gut microbiome on maternal nutritional status during pregnancy, effect on pregnancy outcomes and infant health in rural Pakistan: study protocol for a prospective, longitudinal observational study
Authors: Wasan Yaqub , Baxter Jo-Anna B , Spiegel-Feld Carolyn , Begum Kehkashan , Rizvi Arjumand , Iqbal Junaid , Hulst Jessie , Bandsma Robert , Suleman Shazeen , Soofi Sajid , Parkinson John , Bhutta Zulfiqar Ahmed
Published: August 2024

Introduction

Undernutrition during pregnancy is linked to adverse pregnancy and birth outcomes and has downstream effects on the growth and development of children. The gut microbiome has a profound influence on the nutritional status of the host. This phenomenon is understudied in settings with a high prevalence of undernutrition, and further investigation is warranted to better understand such interactions.

Methods and analysis

This is a prospective, longitudinal observational study to investigate the relationship between prokaryotic and eukaryotic microbes in the gut and their association with maternal body mass index (BMI), gestational weight gain, and birth and infant outcomes among young mothers (17–24 years) in Matiari District, Pakistan. We aim to enrol 400 pregnant women with low and normal BMIs at the time of recruitment (<16 weeks of gestation). To determine the weight gain during pregnancy, maternal weight is measured in the first and third trimesters. Gut microbiome dynamics (bacterial and eukaryotic) will be assessed using 16S and 18S rDNA surveys applied to the maternal stool samples. Birth outcomes include birth weight, small for gestational age, large for gestational age, preterm birth and mortality. Infant growth and nutritional parameters include WHO z-scores for weight, length and head circumference at birth through infancy. To determine the impact of the maternal microbiome, including exposure to pathogens and parasites on the development of the infant microbiome, we will analyse maternal and infant microbiome composition, micronutrients in serum using metallomics (eg, zinc, magnesium and selenium) and macronutrients in the stool. Metatranscriptomics metabolomics and markers of inflammation will be selectively deployed on stool samples to see the variations in dietary intake and maternal nutritional status. We will also use animal models to explore the bacterial and eukaryotic components of the microbiome.

Ethics and dissemination

The study is approved by the National Bioethics Committee (NBC) in Pakistan, the Ethics Review Committee (ERC) at Aga Khan University and the Research Ethics Board (REB) at the Hospital for Sick Children, and findings will be published in peer-reviewed journals.

Trial registration number

NCT05108675.
Patient experience in bariatric surgery: protocol of a French narrative inquiry and qualitative analysis
Authors: Vignot Marina , Jung Camille , Bathaei Sarah , Lazzati Andrea , Gateau Valérie , Angeli Frederica , Delorenzo Christian
Published: August 2024

Introduction

The quality of hospital care, especially surgery, is traditionally assessed using indicators derived from healthcare databases or safety indicators. Given the growing importance of placing the patient at the heart of care evaluation, the use of questionnaires such as the Patient-Reported Experience Measures and Patient-Reported Outcome Measures has become widespread in recent years. However, these tools—addressing factors such as satisfaction, pain management or wait times—only imperfectly reflect the patient’s experience, and all such attempts at patient-centred care quality assessment rely on questions or indicators defined in advance by healthcare providers and health authorities. A biopsychosocial model may allow to better understand the patient experience and to improve care pathways. This study seeks to construct a narrative of the bariatric surgical care journey with instruments from narrative inquiry, propose a metanarrative that can serve as a basis for more sophisticated and reliable patient-focused care quality models and define indicators linked to patients’ feelings and stories.

Methods and analysis

To achieve these aims, 16 bariatric surgical patients at the hospital of Créteil, France (Centre Hospitalier Intercommunal de Créteil), will be included and interviewed once before and twice after surgery, at months 3 and 6. Narratives collected will be used to construct a metanarrative intended to encompass all possible narratives. This metanarrative may ultimately inform new patient care quality indicators, furthering care focused on patients and tailored to their needs and predispositions.

Ethics and dissemination

The study is funded by the Group of Clinical Research and Innovation in Île-de-France and was approved by CPP SUD-EST VI Clermont-Ferrand (France) Research Ethics Committee. The results will be submitted for publication in peer-reviewed journals. The patient associations will be approached for the dissemination of the study results.

Trial registration number

NCT05092659.
Identifying pain profiles in employees including work-related factors and pain perceptions: a cross-sectional study in Belgian companies
Authors: Keyaerts Stijn , Godderis Lode , Vanden Abeele Vero , Daenen Liesbeth
Published: August 2024

Objectives

Studies usually investigate a limited number or a predefined combinations of risk factors for sickness absence in employees with pain. We examined frequently occurring combinations across a wide range of work-related factors and pain perceptions.

Design

Cross-sectional study.

Setting

Belgian companies that are under supervision of IDEWE, an external service for prevention and protection at work.

Participants

In total, 249 employees experiencing pain for at least 6 weeks were included and filled out an online survey.

Outcomes

Latent profile analysis was used to differentiate profiles of work-related factors (physical demands, workload, social support and autonomy) and pain perceptions (catastrophising, fear-avoidance beliefs and pain acceptance). Subsequently, profiles were compared on sociodemographics (age, gender, level of education, work arrangement, duration of complaints, multisite pain and sickness absence in the previous year) and predictors of sickness absence (behavioural intention and perceived behavioural control).

Results

Four profiles were identified. Profile 1 (38.2%) had favourable scores and profile 4 (14.9%) unfavourable scores across all indicators. Profile 2 (33.3%) had relatively high physical demands, moderate autonomy levels and favourable scores on the other indicators. Profile 3 (13.7%) showed relatively low physical demands, moderate autonomy levels, but unfavourable scores on the other indicators. Predictors of profiles were age (OR 0.93 and 95% CI (0.89 to 0.98)), level of education (OR 0.28 and 95% CI (0.1 to 0.79)) and duration of sickness absence in the previous year (OR 2.29 and 95% CI (0.89 to 5.88)). Significant differences were observed in behavioural intention (χ2=8.92, p=0.030) and perceived behavioural control (χ2=12.37, p=0.006) across the four profiles.

Conclusion

This study highlights the significance of considering the interplay between work-related factors and pain perceptions in employees. Unfavourable scores on a single work factor might not translate into maladaptive pain perceptions or subsequent sickness absence, if mitigating factors are in place. Special attention must be devoted to employees dealing with unfavourable working conditions along with maladaptive pain perceptions. In this context, social support emerges as an important factor influencing sickness absence.
Case management in primary healthcare for people with complex needs to improve integrated care: a large-scale implementation study protocol
Authors: Hudon Catherine , Chouinard Maud-Christine , Doucet Shelley , Piccinini-Vallis Helena , Fairman Kimberly , Sampalli Tara , Zed Joanna , Brodeur Magaly , Chênevert Denis , Dépelteau Andréa , Dupont Mariève , Karam Marlène , Légaré France , Luke Alison , Macdonald Marilyn , Morvannou Adele , Ramsden Vivian R , Rodriguez Del Barrio Lourdès , Wong Sabrina T , Lambert Mireille , Bisson Mathieu , Schwarz Charlotte , Benoit René , Poirier Marie-Dominique , Rock-Hervieux Audrey-Lise , Rubenstein Donna , Wilhelm Linda
Published: August 2024

Introduction

Case management (CM) is among the most studied effective models of integrated care for people with complex needs. The goal of this study is to scale up and assess CM in primary healthcare for people with complex needs.

Methods and analysis

The research questions are: (1) which mechanisms contribute to the successful scale-up of CM for people with complex needs in primary healthcare?; (2) how do contextual factors within primary healthcare organisations contribute to these mechanisms? and (3) what are the relationships between the actors, contextual factors, mechanisms and outcomes when scaling-up CM for people with complex needs in primary healthcare? We will conduct a mixed methods Canadian interprovincial project in Quebec, New-Brunswick and Nova Scotia. It will include a scale-up phase and an evaluation phase. At inception, a scale-up committee will be formed in each province to oversee the scale-up phase. We will assess scale-up using a realist evaluation guided by the RAMESES checklist to develop an initial programme theory on CM scale-up. Then we will test and refine the programme theory using a mixed-methods multiple case study with 10 cases, each case being the scalable unit of the intervention in a region. Each primary care clinic within the case will recruit 30 adult patients with complex needs who frequently use healthcare services. Qualitative data will be used to identify contexts, mechanisms and certain outcomes for developing context–mechanism–outcome configurations. Quantitative data will be used to describe patient characteristics and measure scale-up outcomes.

Ethics and dissemination

Ethics approval was obtained. Engaging researchers, decision-makers, clinicians and patient partners on the study Steering Committee will foster knowledge mobilisation and impact. The dissemination plan will be developed with the Steering Committee with messages and dissemination methods targeted for each audience.
Barriers and facilitators to implementing psychosocial digital health interventions for older adults presenting to emergency departments: a scoping review protocol
Authors: Davison Neve , Waddell Alex , Chandrasekara Dharshani , Tran Thach , Hammarberg Karin , Kirkman Maggie , Nimesh Seema , Lowthian Judy A , Olivier Patrick , Romero Lorena , Fisher Jane , Dwyer Rosamond
Published: August 2024

Introduction

Older adults can face challenges when seeking care from emergency departments (EDs) due to presenting with multiple comorbidities and non-specific symptoms. Psychosocial care is a possible target to help improve ED care for this population. It is possible that digital health technologies can be implemented within emergency settings to improve the provision of psychosocial care. However, it is unclear what the barriers and facilitators are to implementing digital psychosocial interventions for older adults presenting to the ED. Therefore, the scoping review aims to determine what are these barriers and facilitators.

Methods and analysis

The scoping review will be conducted in line with the Joanna Briggs Institute guidelines and will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. The databases Medline, Embase, PsycINFO and Scopus will be searched. The search strategy will be developed in consultation with a specialist research librarian and will cover three key concepts: EDs, digital health technologies and older adults. Additionally, the first 100 hits of a Google Scholar search will be screened for inclusion. We will include both qualitative and quantitative studies that investigate ED digital interventions for psychosocial care where the primary focus is the views, attitudes, experiences and perceptions of patients, families and staff. After extracting all data, analysis and synthesis will follow the ‘best-fit framework synthesis’ approach and the Theoretical Domains Framework will be used to identify barriers and facilitators.

Ethics and dissemination

Ethics approval is not required for this scoping review since only publicly available data will be analysed and appraised. The findings of the scoping review will be disseminated through peer-reviewed publications and conference presentations.
Changing trend of cataract blindness and visual outcomes after cataract surgery in adults aged 50 years and older: findings from the national eye surveys in Malaysia
Authors: Salowi Mohamad Aziz , Naing Nyi Nyi , Mustafa Norasyikin , Wan Nawang Wan Radziah , Sharudin Siti Nurhuda , Ngah Nor Fariza
Published: August 2024

Background/aims

Population surveys are required to measure the prevalence of cataract blindness in the community. We conducted simultaneous surveys in two regions in Malaysia in 2023 to estimate the prevalence of untreated cataract, measure the visual outcomes after cataract surgery and compare the results with the survey in 2014.

Methods

The surveys were done in Eastern and Sarawak administrative regions using the rapid assessment of avoidable blindness technique. It involved a multistage cluster sampling method, each cluster comprising 50 residents aged 50 years and older. The prevalence of cataract was determined through a visual acuity (VA) check and eye examination. The VA of those who had undergone cataract surgery was measured, and the findings were compared with the previous survey.

Results

A total of 9709 subjects, 50 years old and older, were examined (percentages of response were 94.5% and 96.2% for Eastern and Sarawak, respectively). Comparing the current to the previous survey in 2014, the prevalence of cataract at all levels of surgical thresholds (except unilateral VA <6/60 and <6/18 in the Eastern) was reduced. The percentages of cataract surgery visual outcomes with good VA (6/12) were improved, and those with poor VA (<6/60) were reduced in both regions.

Conclusion

There was a reduction in cataract prevalence and improved visual outcomes in both regions. These favourable results could be attributed to the surgical performance monitoring initiatives and the community cataract programme implemented soon after the survey in 2014.
Clinical presentation, diagnosis and management of multisystem inflammatory syndrome in children (MIS-C): a systematic review
Authors: Abbas Qalab , Ali Haider , Amjad Fatima , Hussain Muhammad Zaid Hamid , Rahman Abdu R , Khan Maryam Hameed , Padhani Zahra A , Abbas Fatima , Imam Danyal , Alikhan Zuviya , Belgaumi Sameer M. , Mohsin Shazia , Sattar Faiza , Siddiqui Arsalan , Lassi Zohra S , Das Jai K
Published: August 2024

Background

Knowledge about multisystem inflammatory syndrome in children (MIS-C) is evolving, and evidence-based standardised diagnostic and management protocols are lacking. Our review aims to summarise the clinical and diagnostic features, management strategies and outcomes of MIS-C and evaluate the variances in disease parameters and outcomes between high-income countries (HIC) and middle-income countries (MIC).

Methods

We searched four databases from December 2019 to March 2023. Observational studies with a sample size of 10 or more patients were included. Mean and prevalence ratios for various variables were pooled by random effects model using R. A mixed generalised linear model was employed to account for the heterogeneity, and publication bias was assessed via funnel and Doi plots. The primary outcome was pooled mean mortality among patients with MIS-C. Subgroup analysis was conducted based on the income status of the country of study.

Results

A total of 120 studies (20 881 cases) were included in the review. The most common clinical presentations were fever (99%; 95% CI 99.6% to 100%), gastrointestinal symptoms (76.7%; 95% CI 73.1% to 79.9%) and dermatological symptoms (63.3%; 95% CI 58.7% to 67.7%). Laboratory investigations suggested raised inflammatory, coagulation and cardiac markers. The most common management strategies were intravenous immunoglobulins (87.5%; 95% CI 82.9% to 91%) and steroids (74.7%; 95% CI 68.7% to 79.9%). Around 53.1% (95% CI 47.3% to 58.9%) required paediatric intensive care unit admissions, and overall mortality was 3.9% (95% CI 2.7% to 5.6%). Patients in MIC were younger, had a higher frequency of respiratory distress and evidence of cardiac dysfunction, with a longer hospital and intensive care unit stay and had a higher mortality rate than patients in HIC.

Conclusion

MIS-C is a severe multisystem disease with better mortality outcomes in HIC as compared with MIC. The findings emphasise the need for standardised protocols and further research to optimise patient care and address disparities between HIC and MIC.

PROSPERO registration number

CRD42020195823.
Improving management of eosinophilic oesophagitis in adults in the UK: proposal for an integrated care pathway
Authors: Dhar Anjan , Attwood Stephen , Basu Kumar , Carter Jemma S , Cooney Joseph , Dunn Jason , Haboubi Hasan , Jehangir Amir , Pitcher Maxton , Sloan Marion , Wong Terry , Singh Jyotika
Published: August 2024

Eosinophilic oesophagitis (EoE) is a chronic condition characterised by solid-food dysphagia and food bolus obstruction due to T-helper cell-driven eosinophilic infiltration of the oesophageal epithelium and submucosal fibrosis. Suboptimal management results in delayed diagnosis, repeated food bolus obstructions and hospital attendances, inappropriate referral and treatment, increased healthcare resource use, and impaired quality of life. A group of clinicians with an interest in EoE deliberated on the current care pathways and evidence of best practice to develop an integrated care pathway to optimise the diagnosis and management of EoE. Key recommendations include suspecting EoE in patients presenting with food bolus obstruction or dysphagia; referring to gastroenterology and for oesophago-gastro-duodenoscopy promptly; taking at least six biopsies from multiple sites (ideally three) to diagnose EoE based on >15 eosinophils/0.3 mm2oesophageal epithelium; using budesonide orodispersible tablets, as the only UK-licensed therapy for EoE for induction of remission and maintenance; arranging regular oesophago-gastro-duodenoscopies, gastroenterology follow-up and maintenance therapy due to the high relapse rate; and involving primary care to manage follow-on prescribing.