bluuebunny/crossref_metadata_2025 huggingface dataset:
Acidic pH modulates
Burkholderia cenocepacia
antimicrobial susceptibility in the cystic fibrosis nutritional environment
Authors: Morales L. Daniela , Av-Gay Yossef , Murphy Michael E. P.
Published: November 2023

Burkholderia cenocepacia
is an opportunistic pathogen correlated with increased disease severity and mortality in cystic fibrosis (CF) patients. One major difficulty when treating these infections in CF is the poor relationship between
in vitro
susceptibility and clinical outcome. Previous analysis of CF sputum samples showed elevated levels of zinc and iron ions and an acidic pH (2.9–6.5) compared to healthy individuals. Additionally,
B. cenocepacia
grows at an acidic pH (~3.5)
in vitro
and persists for 24 h in the intracellular acid compartments of amoebas and macrophages. We seek to understand the impact of acidic pH and increased zinc and iron concentrations on antibiotic susceptibility in the CF nutritional environment. The Synthetic Cystic Fibrosis sputum Media (SCFM) was modified to represent the acidic pH and increased zinc and iron concentrations found in CF sputum (SCFM-FeZn). We found that the nutritional environment modulated
B. cenocepacia
susceptibility to antimicrobials, and more strikingly, acidic pH decreased susceptibility to most antimicrobials used clinically to treat these infections. Finally, we assessed susceptibility against a custom compound library of antimicrobials using SCFM-FeZn agar plates. Out of 591 antibiotics, only 18 were active against
B. cenocepacia
at both neutral and acidic pH. Four of these compounds (novobiocin, coumermycin, mitomycin C, and streptonigrin) were selected for susceptibility assays in liquid culture. Here, we show that acidic pH modulates antimicrobial susceptibility in the CF nutritional environment and that susceptibility testing in media that mimic the host nutritional environment could pave the way to finding new therapies against infections in CF.

IMPORTANCE

Burkholderia cenocepacia
causes severe infections in cystic fibrosis (CF) patients. CF patients are prone to reoccurring infections due to the accumulation of mucus in their lungs, where bacteria can adhere and grow. Some of the antibiotics that inhibit
B. cenocepacia
in the laboratory are not effective for CF patients. A major contributor to poor clinical outcomes is that antibiotic testing in laboratories occurs under conditions that are different from those of sputum. CF sputum may be acidic and have increased concentrations of iron and zinc. Here, we used a medium that mimics CF sputum and found that acidic pH decreased the activity of many of the antibiotics used against
B. cenocepacia
. In addition, we assessed susceptibility to more than 500 antibiotics and found four active compounds against
B. cenocepacia
. Our findings give a better understanding of the lack of a relationship between susceptibility testing and the clinical outcome when treating
B. cenocepacia
infections.
Immune targets to stop future SARS-CoV-2 variants
Authors: Silva Souza Milena , Pires Farias Jéssica , Barros Luiz Wilson , Birbrair Alexander , Durães-Carvalho Ricardo , de Souza Ferreira Luís Carlos , Amorim Jaime Henrique
Published: November 2023

The SARS-COV-2 variants of concern (VOCs) accumulated mutations that confer to the viral particle a higher infectivity as well as a capacity to escape neutralizing antibodies (NAbs) elicited by vaccines. In this study, we aimed to identify immune determinants that can be targeted to control future SARS-CoV-2 VOC. Using an immunoinformatics pipeline, we constructed a first data set consisting of 215 spike (S) protein amino acid sequences of the wild-type SARS-CoV-2, as well as of the Alpha, Beta, Delta, Gamma, and Omicron variants/subvariants (BA.1, BA.2, BA.4, BA.5, XBB, and BQ.1). A second data set was composed of epitope amino acid sequences for NAb as well as for T-cells involved in anti-viral activity, retrieved from the Immune Epitope Database (IEDB). Epitope conservation and population coverage analyses were carried out using the data sets. The localization of fully conserved epitopes in the S protein was performed using PyMOL. As main results, (i) fully conserved epitopes were identified: 28 for NAbs and 53 and 99 for class-I and class-II human leukocyte antigen, respectively; (ii) the fully conserved epitopes were shown to have high coverage in the world population (99.77% class combined); and (iii) the receptor-binding domain (RBD) of the S protein better balanced numbers of epitopes for NAb and T-cells, while the subunit two concentrated the highest numbers of T-cell epitopes. These results indicate that the RBD region holds different kinds of immune targets that could be used in an escape mutation-proof vaccine antigen to control future SARS-CoV-2 variants.

IMPORTANCE

The emergence of SARS-CoV-2 had a major impact across the world. It is true that the collaboration of scientists from all over the world resulted in a rapid response against COVID-19, mainly with the development of vaccines against the disease. However, many viral genetic variants that threaten vaccines have emerged. Our study reveals highly conserved antigenic regions in the vaccines have emerged. Our study reveals highly conserved antigenic regions in the spike protein in all variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) as well as in the wild-type virus. Such immune targets can be used to fight future SARS-CoV-2 variants.
Longitudinal analysis at three oral sites links oral microbiota to clinical outcomes in allogeneic hematopoietic stem-cell transplant
Authors: Heidrich Vitor , Knebel Franciele H. , Bruno Julia S. , de Molla Vinícius C. , Miranda-Silva Wanessa , Asprino Paula F. , Tucunduva Luciana , Rocha Vanderson , Novis Yana , Fregnani Eduardo R. , Arrais-Rodrigues Celso , Camargo Anamaria A.
Published: November 2023

Allogeneic hematopoietic stem-cell transplant (allo-HSCT) is potentially curative for several hematological disorders. Before stem-cell infusion, recipients undergo a conditioning regimen with chemo/radiotherapy and immunosuppressants, requiring the use of antibiotics to treat and prevent infections. This regimen promotes drastic alterations in the recipient’s microbiota, including the oral microbiota, which have been associated with allo-HSCT complications and poor outcomes. However, long-term longitudinal studies on the oral microbiota of allo-HSCT recipients are scarce and disregard the existence of distinct microbiota within the oral cavity. Here, we used 16S rRNA gene sequencing to characterize the longitudinal microbiota dynamics in a prospective cohort of 31 allo-HSCT recipients at three oral sites (gingival crevicular fluid, oral mucosa, and supragingival biofilm). We found declines in bacterial diversity and major shifts in microbiota composition in all oral sites during allo-HSCT, including blooms of potentially pathogenic genera. These blooms in some cases preceded respiratory infections caused by the blooming bacteria. We also noticed that differences in microbiota composition between oral sites were lost during allo-HSCT. Overall, after allo-HSCT, the distinct oral microbiota returned to their preconditioning state, although at variable levels of competence per patient. After stratifying patients based on recovery levels, we found that recoverers of the oral mucosa microbiota composition had earlier reconstitution of normal blood leukocyte counts. Most notably, oral mucosa microbiota recovery was an independent biomarker of better allo-HSCT outcomes. This study highlights the potential clinical impact of the oral microbiota in the allo-HSCT setting and the clinical value of tracking oral microbiota changes during allo-HSCT.

IMPORTANCE

The oral cavity is the ultimate doorway for microbes entering the human body. We analyzed oral microbiota dynamics in allogeneic hematopoietic stem-cell transplant recipients and showed that microbiota injury and recovery patterns were highly informative on transplant complications and outcomes. Our results highlight the importance of tracking the recipient’s microbiota changes during allogeneic hematopoietic stem-cell transplant to improve our understanding of its biology, safety, and efficacy.
A 5000 yr record of coastal uplift and subsidence reveals multiple source faults for past earthquakes on the central Hikurangi margin, New Zealand
Authors: Pizer Charlotte , Clark Kate , Howarth Jamie , Howell Andrew , Delano Jaime , Hayward Bruce W. , Litchfield Nicola
Published: November 2023

Prehistoric records of subduction earthquakes are often distinguished by evidence of synchronous widespread coastal deformation, the extent of which negates the plausibility of alternative source faults. At the Hikurangi subduction margin in New Zealand, untangling the record of subduction interface ruptures is complicated. Large earthquake age uncertainties inhibit unique solutions of along-strike correlations, and complex patterns of coastal deformation caused by upper-plate faulting prevent reliable indication of source faults. In this work, we improved paleoearthquake reconstructions on the central Hikurangi margin with a new, well-constrained 5000 yr earthquake record from Pakuratahi Valley near Napier, North Island, New Zealand. Evidence of laterally extensive paleoenvironmental changes is consistent with coseismic subsidence and coseismic uplift in large earthquakes. Radiocarbon dates on fragile terrestrial macrofossils and tephra isochrons were used to construct robust age models that yielded earthquake ages of 4839–4601 calibrated (cal.) yr B.P., 3630–3564 cal. yr B.P., 2687–2439 cal. yr B.P., and 1228–823 cal. yr B.P. Integration of these ages with refined earthquake chronology from nearby Ahuriri Lagoon indicated that the next large earthquake impacting the Napier area is more likely to cause coastal subsidence than uplift. Drawing on correlations with cotemporal evidence elsewhere on the central margin, we infer that the overall patterns of coseismic deformation could be generated by either rupture of the subduction interface or upper-plate faults, or both. This inability to separate source faults for past earthquakes limits the efficiency of forecasting future earthquakes. Similar problems of intertwined paleoearthquake signatures likely apply to other plate boundaries, where we recommend cautious interpretation of coastal deformation to accurately address the hazard from both types of source faults.
New biogeochemical insights into Mesozoic terrestrial paleoecology and evidence for omnivory in troodontid dinosaurs
Authors: Cullen Thomas M. , Cousens Brian L.
Published: November 2023

The Cretaceous paleocommunities of North America preserve a rich record of biodiversity that suggests many species occupied narrow biogeographic ranges in comparison to their ecological equivalents in extant systems. How taxa in these systems partitioned their niches and structured their communities can be difficult to determine from fossils alone, which has led to a variety of hypotheses concerning diets and habitat use. Here, we examine element ratios (Sr/Ca, Ba/Ca) in the enamel of a suite of co-occurring vertebrate taxa sampled from a spatiotemporally constrained interval in the Oldman Formation of Alberta, Canada, to reconstruct trophic structure, and use δ13C, δ18O, and 87Sr/86Sr compositions to test for niche partitioning and habitat use among hadrosaurids, ceratopsids, and ankylosaurs. We also test previously proposed dietary hypotheses of troodontid theropods.

In large ornithischians, we find Ba/Ca and Sr/Ca ratios that are consistent with herbivory, with hadrosaurs distinct from ceratopsids and ankylosaurids in their 87Sr/86Sr ranges, a pattern that is indicative of differences in habitat use/breadth, dietary plant sources, and feeding height. The sampled mammals, varanoid lizards, dromaeosaurids, and tyrannosaurids preserve a gradient of lower Sr/Ca and Ba/Ca ratios that is consistent with animal-dominant omnivorous to faunivorous diets. Troodontids, which have been variably hypothesized as either faunivorous, omnivorous, or herbivorous due to their distinct and unusual dentition, preserve Sr/Ca and Ba/Ca ratios that fall between those of the ornithischians and the dromaeosaurids. From these multi-proxy data, we interpret troodontids as mixed-feeding to plant-dominant omnivores. These proxies represent a valuable tool for understanding the trophic and community ecology of Cretaceous ecosystems and hold enormous potential for future research in paleobiology.
Expanding the metamorphic devolatilization model: Komatiites as a source for orogenic gold deposits in high-grade metamorphic rocks
Authors: Yu Chang , Zhong Richen , Tomkins Andrew G. , Cui Hao , Chen Yanjing
Published: November 2023

Orogenic gold deposits contribute the largest proportion of the world’s gold reserves, and the source of their ore-forming components has been recognized as the metamorphic devolatilization of metapelites or metabasites across the greenschist- to amphibolite-facies transition. However, hypozonal orogenic gold deposits represent an enigma in this context. Some of these apparently formed in higher-grade metamorphic rocks when temperatures were beyond the wet solidus of quartz-feldspar–bearing rocks; it is therefore puzzling how these fluids were generated in the source and migrated through the crust without causing partial melting. Here, we show that devolatilization of hydrated komatiites, a volumetrically significant lithological unit in Precambrian greenstone belts, is a viable model that can plausibly lead to gold mineralization at amphibolite-facies conditions. Our thermodynamic simulations indicate that subsolidus metamorphic devolatilization of komatiites at ~700 °C (upper amphibolite facies) can unlock significant amounts of gold via dehydration of talc and chlorite. This genetic model is supported by the geochemical characteristics of, and estimated pressure-temperature (P-T) formation conditions of, hypozonal gold deposits and the intimate spatiotemporal association between hypozonal deposits and komatiites in greenstone belts. This work expands the P-T range of the metamorphic devolatilization model and enhances its robustness in explaining gold mineralization in metamorphic terranes.
Sustained deformation across the Sub-Himalayas since 200 ka
Authors: Bouscary Chloé , King Georgina E. , Grujic Djordje , Lavé Jérôme , Almeida Rafael , Hetényi György , Herman Frédéric
Published: November 2023

The Himalayan Main Frontal Thrust (MFT) currently accommodates approximately half, i.e., 12–23 mm/yr, of the convergence between the Indian and Eurasian tectonic plates by uplift and deformation of the Sub-Himalayas. While deformation is well documented at modern and million-year time scales, almost no quantitative data are available that constrain Quaternary time scale deformation rates along and within this key tectonic unit. Filling this knowledge gap is crucial to better understanding tectonics and the seismic cycle in this densely populated Himalayan region. We quantify exhumation rates in the Sub-Himalayas using the recently established luminescence thermochronometry technique over time scales of 105 yr, which documents exhumation over the final few kilometers of Earth’s crust. The ultra-low closure temperature of luminescence thermochronometry enables us to resolve thermal histories from the Siwalik Group (Nepal) rocks, which have experienced maximum burial temperatures of ~120 °C. An extensive set of 33 samples was collected from western Nepal to eastern Bhutan, from which 22 yield exhumation rates of ~3–11 mm/yr over the past ~200 k.y. We converted these values to minimum cumulative thrust slip rates of ~6–22 mm/yr, assuming a thrust dip angle of 30°. Our luminescence thermochronometry results show that the Sub-Himalayan fold-and-thrust belt, particularly the MFT, accommodates at least 62% of Himalayan convergence since at least 200 ka. Our data also show activity of some intra-Siwalik thrusts throughout this period, implying that internal deformation of the orogenic wedge and strain partitioning may have occurred.
Source and Generation Parameters of the Granitoid Melts of the Archean Charnockite–Enderbite Complex in Karelia, with Reference to the Pon’goma-Navolok Massif
Authors: Kozlovskii V. M. , Kurdyukov E. B. , Yakushik M. A. , Travin V. V. , Zinger T. F. , Yakushev A. I. , Fugzan M. M. , Kirnozova T. I. , Ushakova S. A.
Published: November 2023

Abstract—

The paper presents authors’ original detailed data on rocks of the Archean Pon’goma-Navolok charnockite−enderbite complex in northern Karelia. The rocks practically have not been modified and are preserved within a rigid block among Paleoproterozoic zones of ductile deformations and metamorphism. The geochemistry of the rocks and their isotope−geochemical features indicate that the protolith from which the enderbite melts of the main phase of the massif were derived may have been amphibolites. The enderbite melts were derived from these amphibolites under the effect of K2O-, Na2O-, and SiO2-bearing fluids; and the enderbites were subsequently charnockitized with the involvement of fluids enriched in K2O and SiO2. Physicochemical modeling indicates that the enderbite melt was derived from the amphibolite protolith at a depth of about 45 km (P = 14.8 kbar, T = 1030−1080°C) under the effect of saline H2O−CO2 fluid. Comparison of the P−T parameters of the granulite-facies metamorphism of the metabasites and the parameters under which the enderbite melts were derived indicates that Archean granulite-facies metamorphism in the Belomorian belt in northern Karelia was of contact but not regional nature and was induced by the high-temperature field of an emplaced enderbite massif. The orthogneisses hosting the Pan’goma-Navolok massif inherit geochemical features of the unsheared, ungneissose, and unmetamorphosed enderbites. This means that enderbites analogous to those of the Pan’goma-Navolok massif may have served as the protolith of some of the orthogneisses, and that enderbites may have been spread more widely in the Archean than the currently preserved single enderbite massifs.
Erratum to: An Equation for the Calculation of Saturated Water Contents in Silicate Melts: A New Version
Authors: Gnuchev Ya. Yu. , Bychkov D. A. , Koptev-Dvornikov E. V.
Published: November 2023

An Erratum to this paper has been published: https://doi.org/10.1134/S0016702923210012
Nasal chondromesenchymal hamartoma (NCMH): a rare DICER1-associated tumour in an adult male
Authors: Paraschou Konstantinos , Miller Benjamin , Surda Pavol , Sandison Ann
Published: November 2023

An adult male presented to the ENT clinic with a 1-year history of unilateral nasal blockage. He had presented to another institution 5 years previously with the same issue, undergoing resection of what was reported to be a benign inflammatory polyp with osseous metaplasia. Detailed examination revealed a large mass filling the left nasal cavity. Excisional biopsy and secondary specialist review of pathology revealed nasal chondromesenchymal hamartoma (NCMH) with associated DICER1 mutations. NCMH is a rare, benign tumour of the sinonasal tract, presenting more often in the early childhood, with symptoms related to the site and extent of the tumour. As highlighted in this case, complete excision is mandatory for definitive diagnosis and treatment of NCMH, and an awareness of the association with DICER1 mutation, which can predispose individuals to a range of neoplasia, is key to providing appropriate genetic counselling.
Klinefelter syndrome presenting as metastatic bilateral breast cancer: missed diagnostic opportunities
Authors: Tudor Roxana Maria , Ali Elsheikh Mohammed , Khan Salman Ullah , McDermott John
Published: November 2023

Klinefelter syndrome (KS) is the most common cause of primary hypogonadism in male patients; however, the diagnosis of KS is frequently delayed or missed. This delay can lead to undesirable outcomes for patients, especially considering that individuals with KS have a higher risk of developing specific malignancies, including breast cancer, non-Hodgkin’s lymphoma and mediastinal germ cell tumours. We present a case of a male patient in his 60s, where the established diagnosis of metastatic bilateral breast cancer prompted us to investigate and subsequently confirm a diagnosis of KS. This case highlights the diagnostic challenges of KS and emphasises the unfavourable consequences of a delayed diagnosis. We aim to raise awareness and enhance physicians’ understanding of KS and its non-reproductive manifestations, with a view to promote early recognition and improve patient outcomes.
Treatment of lower urinary tract symptoms in men in primary care using a conservative intervention: cluster randomised controlled trial
Authors: Drake Marcus J , Worthington Jo , Frost Jessica , Sanderson Emily , Cochrane Madeleine , Cotterill Nikki , Fader Mandy , McGeagh Lucy , Hashim Hashim , Macaulay Margaret , Rees Jonathan , Robles Luke A , Taylor Gordon , Taylor Jodi , Ridd Matthew J , MacNeill Stephanie J , Noble Sian , Lane J Athene
Published: November 2023

Objective

To determine whether a standardised and manualised care intervention in men in primary care could achieve superior improvement of lower urinary tract symptoms (LUTS) compared with usual care.

Design

Cluster randomised controlled trial.

Setting

30 National Health Service general practice sites in England.

Participants

Sites were randomised 1:1 to the intervention and control arms. 1077 men (≥18 years) with bothersome LUTS recruited between June 2018 and August 2019: 524 were assigned to the intervention arm (n=17 sites) and 553 were assigned to the usual care arm (n=13 sites).

Intervention

Standardised information booklet developed with patient and expert input, providing guidance on conservative and lifestyle interventions for LUTS in men. After assessment of urinary symptoms (manualised element), general practice nurses and healthcare assistants or research nurses directed participants to relevant sections of the manual and provided contact over 12 weeks to assist with adherence.

Main outcome measures

The primary outcome was patient reported International Prostate Symptom Score (IPSS) measured 12 months after participants had consented to take part in the study. The target reduction of 2.0 points on which the study was powered reflects the minimal clinically important difference where baseline IPSS is <20. Secondary outcomes were patient reported quality of life, urinary symptoms and perception of LUTS, hospital referrals, and adverse events. The primary intention-to-treat analysis included 887 participants (82% of those recruited) and used a mixed effects multilevel linear regression model adjusted for site level variables used in the randomisation and baseline scores.

Results

Participants in the intervention arm had a lower mean IPSS at 12 months (adjusted mean difference −1.81 points, 95% confidence interval −2.66 to −0.95) indicating less severe urinary symptoms than those in the usual care arm. LUTS specific quality of life, incontinence, and perception of LUTS also improved more in the intervention arm than usual care arm at 12 months. The proportion of urology referrals (intervention 7.3%, usual care 7.9%) and adverse events (intervention seven events, usual care eight events) were comparable between the arms.

Conclusions

A standardised and manualised intervention in primary care showed a sustained reduction in LUTS in men at 12 months. The mean difference of −1.81 points (95% confidence interval −0.95 to −2.66) on the IPSS was less than the predefined target reduction of 2.0 points.

Trial registration

ISRCTN Registry
ISRCTN11669964
.
Reframing the Three Delays framework: factors influencing referrals to facilities by matrones in rural Haiti
Authors: Jean-Baptiste Milenka , Millien Christophe , Pognon Pierre Ricard , Casella Jean-Baptiste Meredith
Published: November 2023

In Haiti, there has been limited research on the experiences of traditional birth attendants/matrones when they decide to refer and accompany pregnant women to the facility for giving birth. Understanding this contextualised experience could help to strengthen programming aimed at improving maternal, neonatal, and child health (MNCH) outcomes in rural Haiti. This paper describes the qualitative findings from seven focus group discussions (FGDs) with matrones regarding their experience of referring pregnant women to facilities in Haiti’s Central Plateau. Each FGD was conducted in Haitian Kreyol and audio recorded. Recordings were transcribed, translated to English, and thematically analysed. A conceptual model visualising factors influencing matrone decision-making was then developed using an adapted version of the Three Delays framework. Findings from this study show that matrones face a complex, multilayered web of intertwining factors related to attitudes and beliefs around their role, resource availability, and perceptions around quality of care and treatment. Each factor corresponds to a delay in the Three Delays framework. The factors can occur at the same time or each can occur individually at different times, and influence the decision to refer. The complexity of factors identified reflects the need to reassess the Three Delays framework so that it accounts for the intertwining, cyclical complexities faced by those trying to access the facility amidst the backdrop of both time and the community/social contexts. Results further reflect the need for strengthened health systems that better facilitate matrone facility-based referrals, improving outcomes for all parties involved and bridging the gap between homes/ communities and facilities. This calls for better integration of the matrones into the formal health system to systematically strengthen the continuum of MNCH health services provided from home to facility.
The international diffusion of food innovations and the nutrition transition: retrospective longitudinal evidence from country-level data, 1970–2010
Authors: Disdier Anne-Célia , Etilé Fabrice , Rotunno Lorenzo
Published: November 2023

Introduction

There is a lack of quantitative evidence on the role of food innovations—new food ingredients and processing techniques—in the nutrition transition.

Objective

Document the distribution of food innovations across 67 high-income (HIC) and middle-income (MIC) countries between 1970 and 2010, and its association with the nutritional composition of food supply.

Methods

We used all available data on food patents, as compiled by the European Patent Office, to measure food innovations. We considered innovations directly received by countries from inventors seeking protection in their territories, and those embedded in processed food imports. Food and Agricultural Organization data were used to estimate the associations between international diffusion of food innovations and trends in total food supply and its macronutrient composition, after adjusting for confounding trends in demand-side factors. We identified the role of trade by simulating the changes in average diet due to innovations embedded in food imports.

Results

Trends in food innovations were positively and significantly associated with changes in daily per capita calorie supply available for human consumption in MIC between 1990 and 2010 (elasticity of 0.027, 95% CI 0.019 to 0.036). Food innovations were positively correlated with the share of animal and free fats in total food supply (elasticities of 0.044, 95% CI 0.030 to 0.058 for MIC between 1970 and 1989 and 0.023, 95% CI 0.003 to 0.043 for HIC between 1990 and 2010). Food innovations were associated with substitutions from complex carbohydrates towards sugars in total food supply for MIC after 1990 (elasticities of −0.037, 95% CI −0.045 to −0.029 for complex carbs, 0.082, 95% CI 0.066 to 0.098 for sugars). For these countries, the trade channel capturing access to innovations through imports of processed food played a key role.

Conclusion

Policy-makers should consider the impacts of the international diffusion of food innovations in assessing the costs and benefits of international trade regulations.
Estimated impact of the UK soft drinks industry levy on childhood hospital admissions for carious tooth extractions: interrupted time series analysis
Authors: Rogers Nina Trivedy , Conway David I , Mytton Oliver , Roberts Chrissy H , Rutter Harry , Sherriff Andrea , White Martin , Adams Jean
Published: November 2023

Introduction

Tooth extraction due to dental caries is associated with socioeconomic deprivation and is a major reason for elective childhood hospital admissions in England. Consumption of sugar-sweetened beverages is a risk factor for dental caries. We examined whether the soft drinks industry levy (SDIL), announced in March 2016 and implemented in April 2018, was associated with changes in incidence rates of hospital admissions for carious tooth extraction in children, 22 months post-SDIL implementation.

Methods

Changes in incidence rates of monthly National Health Service hospital admissions for extraction of teeth due to a primary diagnosis of dental caries (International Classification of Diseases; ICD-10 code: K02) in England, between January 2012 and February 2020, were estimated using interrupted time series and compared with a counterfactual scenario where SDIL was not announced or implemented. Periodical changes in admissions, autocorrelation and population structure were accounted for. Estimates were calculated overall, by Index of Multiple Deprivation (IMD) fifths and by age group (0–4 years, 5–9 years, 10–14 years, 15–18 years).

Results

Compared with the counterfactual scenario, there was a relative reduction of 12.1% (95% CI 17.0% to 7.2%) in hospital admissions for carious tooth extractions in all children (0–18 years). Children aged 0–4 years and 5–9 years had relative reductions of 28.6% (95% CI 35.6% to 21.5%) and 5.5% (95% CI 10.5% to 0.5%), respectively; no change was observed for older children. Reductions were observed in children living in most IMD areas regardless of deprivation.

Conclusion

The UK SDIL was associated with reductions in incidence rates of childhood hospital admissions for carious tooth extractions, across most areas regardless of deprivation status and especially in younger children.

Trial registration number

ISRCTN18042742.
Developing and externally validating a machine learning risk prediction model for 30-day mortality after stroke using national stroke registers in the UK and Sweden
Authors: Wang Wenjuan , Otieno Josline A , Eriksson Marie , Wolfe Charles D , Curcin Vasa , Bray Benjamin D
Published: November 2023

Objectives

We aimed to develop and externally validate a generalisable risk prediction model for 30-day stroke mortality suitable for supporting quality improvement analytics in stroke care using large nationwide stroke registers in the UK and Sweden.

Design

Registry-based cohort study.

Setting

Stroke registries including the Sentinel Stroke National Audit Programme (SSNAP) in England, Wales and Northern Ireland (2013–2019) and the national Swedish stroke register (Riksstroke 2015–2020).

Participants and methods

Data from SSNAP were used for developing and temporally validating the model, and data from Riksstroke were used for external validation. Models were developed with the variables available in both registries using logistic regression (LR), LR with elastic net and interaction terms and eXtreme Gradient Boosting (XGBoost). Performances were evaluated with discrimination, calibration and decision curves.

Outcome measures

The primary outcome was all-cause 30-day in-hospital mortality after stroke.

Results

In total, 488 497 patients who had a stroke with 12.4% 30-day in-hospital mortality were used for developing and temporally validating the model in the UK. A total of 128 360 patients who had a stroke with 10.8% 30-day in-hospital mortality and 13.1% all mortality were used for external validation in Sweden. In the SSNAP temporal validation set, the final XGBoost model achieved the highest area under the receiver operating characteristic curve (AUC) (0.852 (95% CI 0.848 to 0.855)) and was well calibrated. The performances on the external validation in Riksstroke were as good and achieved AUC at 0.861 (95% CI 0.858 to 0.865) for in-hospital mortality. For Riksstroke, the models slightly overestimated the risk for in-hospital mortality, while they were better calibrated at the risk for all mortality.

Conclusion

The risk prediction model was accurate and externally validated using high quality registry data. This is potentially suitable to be deployed as part of quality improvement analytics in stroke care to enable the fair comparison of stroke mortality outcomes across hospitals and health systems across countries
The risk factors for and the frequency and outcomes of subsyndromal delirium among patients who have undergone cardiac surgery: a protocol for systematic review and meta-analysis
Authors: Gao Yan , Bai Xue , Zhang Huan , Yang Li , Wu Taiqin , Gan Xiuni
Published: November 2023

Introduction

Several key symptoms must be present for the accurate diagnosis of patients with postoperative cardiac delirium. Some patients present with symptoms of delirium but do not meet the diagnostic criteria for delirium; such individuals are considered to have having subsyndromal delirium (SSD). SSD is associated with misdiagnosis and poor outcomes. However, to date, no systematic review (SR) has examined the frequency of, risk factors for, and outcomes of SSD among adults who have undergone cardiac surgery.

Methods and analysis

The aim of this SR is to identify those studies that have explored SSD after cardiac surgery. MeSH and free entry terms associated with “subsyndromal delirium” and “subclinical delirium” will be used to search for relevant studies. The PubMed, Web of Science, OVID, Cochrane Library, CINAHL, EMBASE, PsycINFO, China National Knowledge Infrastructure, Wanfang data, VIP database and SinoMed will be searched from inception to the date of retrieval without any restrictions. The primary outcomes will be the frequency of SSD, the risk factors for SSD, and the outcomes of SSD. Analyses will be performed using STATA V.16.0, and descriptive analyses will be performed if the data are not suitable for meta-analysis (ie, data with significant heterogeneity or from different comparisons).

Ethics and dissemination

The SR will examine the frequency of, risk factors for and outcomes of SSD in adults who have undergone cardiac surgery. The results will provide guidance for the identification of knowledge gaps in this field, and areas for further research will be highlighted. The review protocol will be submitted for publication in peer-reviewed journals for dissemination of the findings. Individual patient data will not be included in this protocol, so ethical approval will not be needed.

PROSPERO registration number

CRD42022379211.
External validation of a cardiovascular risk model for Omani patients with type 2 diabetes mellitus: a retrospective cohort study
Authors: Al Oraimi Fatema , Al Rawahi Amani , Al Harrasi Amira , Albusafi Sarah , Al-Manji Laila Mohammed , Alrawahi Abdul Hakeem , Al Salmani Asma Ali
Published: November 2023

Objectives

To externally validate a recently developed cardiovascular disease (CVD) risk model for Omanis with type 2 diabetes mellitus (T2DM).

Design

Retrospective cohort study.

Setting

Nine primary care centres in Muscat Governorate, Oman.

Participants

A total of 809 male and female adult Omani patients with T2DM free of CVD at baseline were selected using a systematic random sampling strategy.

Outcome measures

Data regarding CVD risk factors and outcomes were collected from the patients’ electronic medical records between 29 August 2020 and 2 May 2021. The ability of the model to discriminate CVD risk was assessed by calculating the area under the curve (AUC) of the receiver-operating characteristic curve. Calibration of the model was evaluated using a Hosmer-Lemeshow χ2test and the Brier score.

Results

The incidence of CVD events over the 5-year follow-up period was 4.6%, with myocardial infarction being most frequent (48.6%), followed by peripheral arterial disease (27%) and non-fatal stroke (21.6%). A cut-off risk value of 11.8% demonstrated good sensitivity (67.6%) and specificity (66.5%). The area under the curve (AUC) was 0.7 (95% CI 0.60 to 0.78) and the Brier score was 0.01. However, the overall mean predicted risk was greater than the overall observed risk (11.8% vs 4.6%) and the calibration graph showed a relatively significant difference between predicted and observed risk levels in different subgroups.

Conclusions

Although the model slightly overestimated the CVD risk, it demonstrated good discrimination. Recalibration of the model is required, after which it has the potential to be applied to patients presenting to diabetic care centres elsewhere in Oman.
Health-related quality of life and associated factors among patients with schizophrenia at comprehensive specialised hospitals in the Northwest Ethiopia: a multicentre cross-sectional study
Authors: Tamene Fasil Bayafers , Sema Faisel Dula , Mihiretie Endalamaw Aschale , Siyum Tewodros Solomon , Sendekie Ashenafi Kibret
Published: November 2023

Objectives

The aim of this study was to assess the health-related quality of life (HRQoL) and associated factors among patients with schizophrenia at comprehensive specialised hospitals in Northwest Ethiopia.

Design and setting

A cross-sectional study was conducted among 422 patients with schizophrenia who were followed at comprehensive specialised hospitals in Northwest Ethiopia from 1 June to 30 August 2022.

Participants

All adult patients with schizophrenia who had regular follow-up in the outpatient departments of the selected hospitals were study participants.

Main outcome measures

The main outcome of this study was HRQoL which was measured using the WHO Quality of Life Scale–Bref Version. Data entry and analysis were done using Epi-data version 4.6.1 and SPSS version 24, respectively. Linear regression was used to assess the association between quality of life and independent variables. Variables with a p value <0.05 at a 95% CI were considered statistically significant.

Results

The mean score of the overall Quality of Life Scale–Brief Version was 22.42±3.60. No formal education (ß=−1.53; 95% CI: −2.80 to –0.27), duration of treatment (ß = –3.08; 95% CI: −4.71 to –1.45), comorbidity (ß=−1.14; 95% CI: −1.99 to –0.29), substance use (ß=−0.89; 95% CI: −1.56 to –0.23), extrapyramidal side effects (ß=−2.02; 95% CI: −2.90 to –1.14), non-adherence (ß=−0.83; 95% CI: −1.44 to –0.23), and antipsychotic polypharmacy (ß=−1.77; CI: −2.57 to –0.96) were negatively associated with quality of life.

Conclusion and recommendation

In this study, the social domain was recorded as having the lowest mean score, which may indicate that patients with schizophrenia could need better psychosocial support. Patients with a longer duration of treatment, who had comorbid illnesses, were substance users, developed EPS, were non-adherent to medications and were on antipsychotic polypharmacy, needs critical follow-up to improve HRQoL.
REVISE:Re-Evaluating theInhibition ofStressErosions in the ICU: a randomised trial protocol
Authors: Deane Adam M , Alhazzani Waleed , Guyatt Gordon , Finfer Simon , Marshall John C , Myburgh John , Zytaruk Nicole , Hardie Miranda , Saunders Lois , Knowles Serena , Lauzier Francois , Chapman Marianne J , English Shane , Muscedere John , Arabi Yaseen , Ostermann Marlies , Venkatesh Balasubramanian , Young Paul , Thabane Lehana , Billot Laurent , Heels-Ansdell Diane , Al-Fares Abdulrahman A , Hammond Naomi E , Hall R , Rajbhandari Dorrilyn , Poole Alexis , Johnson Daniel , Iqbal Mobeen , Reis Gilmar , Xie Feng , Cook Deborah J
Published: November 2023

Introduction

TheRe-Evaluating theInhibition ofStressErosions (REVISE) Trial aims to determine the impact of the proton pump inhibitor pantoprazole compared with placebo on clinically important upper gastrointestinal (GI) bleeding in the intensive care unit (ICU), 90-day mortality and other endpoints in critically ill adults. The objective of this report is to describe the rationale, methodology, ethics and management of REVISE.

Methods and analysis

REVISE is an international, randomised, concealed, stratified, blinded parallel-group individual patient trial being conducted in ICUs in Canada, Australia, Saudi Arabia, UK, US, Kuwait, Pakistan and Brazil. Patients≥18 years old expected to remain invasively mechanically ventilated beyond the calendar day after enrolment are being randomised to either 40 mg pantoprazole intravenously or an identical placebo daily while mechanically ventilated in the ICU. The primary efficacy outcome is clinically important upper GI bleeding within 90 days of randomisation. The primary safety outcome is 90-day all-cause mortality. Secondary outcomes include rates of ventilator-associated pneumonia,Clostridioides difficileinfection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine level in the ICU, and duration of mechanical ventilation, ICU and hospital stay. The sample size is 4800 patients; one interim analysis was conducted after 2400 patients had complete 90-day follow-up; the Data Monitoring Committee recommended continuing the trial.

Ethics and dissemination

All participating centres receive research ethics approval before initiation by hospital, region or country, including, but not limited to – Australia: Northern Sydney Local Health District Human Research Ethics Committee and Mater Misericordiae Ltd Human Research Ethics Committee; Brazil: Comissão Nacional de Ética em Pesquisa; Canada: Hamilton Integrated Research Ethics Board; Kuwait: Ministry of Health Standing Committee for Coordination of Health and Medical Research; Pakistan: Maroof Institutional Review Board; Saudi Arabia: Ministry of National Guard Health Affairs Institutional Review Board: United Kingdom: Hampshire B Research Ethics Committee; United States: Institutional Review Board of the Nebraska Medical Centre. The results of this trial will inform clinical practice and guidelines worldwide.

Trial registration number

NCT03374800.
How to extend value-based healthcare to population-based healthcare systems? Defining an outcome-based segmentation model for health authority
Authors: Torkki Paulus , Leskelä Riikka-Leena , Mustonen Pirjo , Linna Miika , Lillrank Paul
Published: November 2023

Objectives

Value-based healthcare (VBHC) is considered the most promising guiding principle for a new generation of health service production. Many countries have attempted to apply VBHC to managerial and clinical decision-making. However, implementation remains in its infancy and varies between countries. The objective of the study is to help health systems implement a value-based approach by building an outcome-based population segmentation model for health authorities (HAs).

Design

First, we define the principles according to which segmentation models in healthcare could be developed. Second, we merge the theoretical characteristics of outcomes with population segmentation dimensions identified in previous literature and design a flow model that establishes population segments from these combinations. We then estimate the size of the segments based on national register data.

Results

The population can be divided into 10 different segments based on relevant outcomes, goals and the outcome measurement logic. These segments consist of healthy, help, increased risk, mild curable without risk, mild curable with risk, severe curable without risk, severe curable with risk, single chronic, multimorbid and terminal. The representatives of Finnish HAs found the segments meaningful for evaluating and managing the healthcare system towards improved population health.

Conclusions

An outcome-based segmentation model for the entire population is needed if an HA wants to steer the healthcare system employing the principles of VBHC. Segmentation should be based on the outcome measurement logic and outcome measurements relevant to each segment and the number of segments has to be limited.
Effects of a laboratory-based aerobic exercise intervention on brain volume and cardiovascular health markers: protocol for a randomised clinical trial
Authors: Molina Hidalgo Cristina , Collins Audrey M , Crisafio Mary E , Grove George , Kamarck Thomas W , Kang Chaeryon , Leckie Regina L , MacDonald Madison , Manuck Stephen B , Marsland Anna L , Muldoon Matthew F , Rasero Javier , Scudder Mark R , Velazquez-Diaz Daniel , Verstynen Timothy , Wan Lu , Gianaros Peter J , Erickson Kirk I
Published: November 2023

Introduction

Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk.

Methods and analysis

In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain–body interactions in the context of cardiovascular health.

Ethics and dissemination

Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule.

Trial registration number

NCT03841669.