bluuebunny/crossref_metadata_2025 huggingface dataset:
Living with schizophrenia and type 2 diabetes and the implication for diabetes self‐care: A qualitative study
Authors: Mikkelsen Tanja Juhl , Agerskov Hanne , Jensen Dorte Moeller , Stenager Elsebeth , Rothmann Mette Juel
Published: February 2024

Aim

To achieve an in‐depth understanding of the challenges associated with diabetes management when having both schizophrenia and type 2 diabetes, while also identifying the needs for improved diabetes self‐care.

Design

The study employed a qualitative explorative design utilizing a phenomenological‐hermeneutic inspired approach, involving field observations and individual semistructured interviews.

Methods

Data were collected during 2020–2021 through 17 field observations of outpatient consultations and 13 individual semistructured interviews. Data, including field notes and verbatim transcribed interviews, underwent analysis following Ricoeur's interpretive philosophy, encompassing three levels: naïve reading, structural analysis and critical interpretation and discussion. This study adheres to the COREQ guidelines for qualitative research.

Results

Three key themes emerged: ‘Diabetes when life is noisy’, ‘Sacrifices and compromises in life’ and ‘The double silence’. Everyday life is significantly affected when having both schizophrenia and T2D. The mental health state dominates in relation to diabetes self‐care and individuals experience challenges balancing between the two conditions. However, there exists a general acknowledgement for diabetes and its long‐term complications as a serious medical condition demanding careful attention and treatment.

Conclusion

Self‐managing two such complex conditions can be overwhelming and make it difficult for the individual to differentiate symptoms and prioritize diabetes care. Moreover, the existing fragmentation within healthcare systems poses communication challenges, resulting in disjointed patient pathways.

Implications for patient care

The study emphasizes the need for a holistic re that addresses the physical, emotional and social challenges. There is also a need for increased awareness and education among informal caregivers and healthcare professionals to foster better understanding and support.
Patient outcomes following medical emergency team review on general wards: Development of predictive models
Authors: Batterbury Anthony , Douglas Clint , Coyer Fiona
Published: February 2024

Aim

To develop and internally validate risk prediction models for subsequent clinical deterioration, unplanned ICU admission and death among ward patients following medical emergency team (MET) review.

Design

A retrospective cohort study of 1500 patients who remained on a general ward following MET review at an Australian quaternary hospital.

Method

Logistic regression was used to model (1) subsequent MET review within 48 h, (2) unplanned ICU admission within 48 h and (3) hospital mortality. Models included demographic, clinical and illness severity variables. Model performance was evaluated using discrimination and calibration with optimism‐corrected bootstrapped estimates. Findings are reported using the TRIPOD guideline for multivariable prediction models for prognosis or diagnosis. There was no patient or public involvement in the development and conduct of this study.

Results

Within 48 h of index MET review, 8.3% (n = 125) of patients had a subsequent MET review, 7.2% (n = 108) had an unplanned ICU admission and in‐hospital mortality was 16% (n = 240). From clinically preselected predictors, models retained age, sex, comorbidity, resuscitation limitation, acuity‐dependency profile, MET activation triggers and whether the patient was within 24 h of hospital admission, ICU discharge or surgery. Models for subsequent MET review, unplanned ICU admission, and death had adequate accuracy in development and bootstrapped validation samples.

Conclusion

Patients requiring MET review demonstrate complex clinical characteristics and the majority remain on the ward after review for deterioration. A risk score could be used to identify patients at risk of poor outcomes after MET review and support general ward clinical decision‐making.

Relevance to clinical practice

Our risk calculator estimates risk for patient outcomes following MET review using clinical data available at the bedside. Future validation and implementation could support evidence‐informed team communication and patient placement decisions.
Effects of phytase enzyme supplementation on growth performance, intestinal morphology and metabolism in Nile tilapia (Oreochromis niloticus)
Authors: Negm Ahmed E. , Abo‐Raya Mohamed H. , Gabr Asmaa M. , Baloza Samar H. , El‐Nokrashy Asmaa , Prince Abdelbary , Arana Daniel , Wang Youji , Abdelazeem Shimaa , Albadrani Ghadeer M. , Al‐Ghadi Muath Q. , Abdeen Ahmed , Shukry Mustafa , El‐Sayed Khalafallah Malik M.
Published: February 2024

Phytase is crucial in enhancing the bioavailability and release of phosphorus and other nutrients bound to phytic acid, making them more bioavailable for animal absorption. This study was carried out to inspect the effect of supplementing low phosphorus (P) diet with di‐calcium phosphate (DCP) and liquid phytase enzyme (LP), which contains 1500 FTU/kg, on growth performance, intestinal morphometry, proximate body chemical composition, blood profile, immunity status, liver mitochondrial enzyme activities, the expression response and economic returns of Nile tilapia (Oreochromis niloticus). Three triplicate groups of fish (initial weight 5.405 ± 0.045 g, N = 90) were fed on three different diets for 90 days. The first was a control diet with zero DCP; the second was a control diet supplemented with 0.71% DCP; the third was a control diet supplemented with 0.03% LP. The groups were designated as CG, DCP and LP, respectively. Results showed that LP induced considerable improvements (p < 0.05) in FBW, body weight gain, weight gain rate, specific growth rate, HIS, viscero‐somatic index, spleen‐somatic index, feed conversion ratio, blood parameters and the histomorphometry assessment of intestinal villi absorptive capacity, compared with the other groups. Also, whole‐body protein and lipid contents pointedly (p < 0.05) increased by LP, compared with the DCP group. A positive response (p < 0.05) to the phytase enzyme was noted in complexes I, III and IV of the mitochondrial liver complex enzyme activity. Likewise, the relative gene expression levels of (GHr‐1, IGF‐1, FAS and LPL) were notably (p < 0.05) upregulated by phytase enzyme, associated with DCP and control groups. Further, phytase recorded the highest total return and profit percentage. It can be concluded that Nile tilapia benefits from using phytase enzyme 1500 FTU/kg at 0.03% without adding DCP in terms of good performance and profits.
A sociology of existence for a late modern world. Basic assumptions and conceptual tools
Authors: Flisbäck Marita , Bengtsson Mattias
Published: February 2024

In the present article, we outline basic assumptions and conceptual tools for a sociology of existence. First, we address man's fundamental conditions of existence: that life's finitude and encounters with the uncertainty of existence are fundamental experiences that construct social relations. Second, we outline how existential meaning‐making and the ability to cope with the unpredictability of life are dependent on power resources, where especially the resource poor may experience ‘existential nausea’. Third, we discuss how existential dilemmas may intensify under certain historical eras. Therefore, studying individuals' existential dilemmas is a tool to examine the dominant social issues at a particular time and place. Fourth, we elaborate on the importance of studying turning points during individuals' life courses, as existential meaning – or lack thereof – becomes particularly salient at these times. This includes an understanding that death and rebirth are experienced in the form of various endings and beginnings in everyday life. Fifth, and finally, we emphasize an analysis in which the direction of people's lives is conceptualized in a broad time perspective, where past, present, and future interact and influence life choices and social relations constructed during a lifetime.
An empirical application of herding behavior and compliance in the COVID‐19 crisis
Authors: Nilsson Helena , Backman Mikaela
Published: February 2024

There is evidence that individuals engage in herding behavior in diverse settings, ranging from fashion choices to financial markets. By examining the exogenous shock caused by the outbreak of COVID‐19 and unique data measuring the footfalls in downtown Jönköping, Sweden, we empirically assess how individuals respond to the restrictions imposed by the government and to the behavior of others, that is, herding. To this end, a regression discontinuity analysis with time as the running variable is applied. We find a negative effect of the restriction on footfalls, indicating that individuals follow the imposed governmental restrictions. However, we also find indications that individuals imitate the actions of others and engage in herd behavior even when the cost of doing so is very high; that is, it could result in severe illness or even death. With the use the unique setting of Sweden, where there have been no enforced lockdowns, we contribute with knowledge related to how effective voluntary restrictions are and the influence of others on one's decision making. Although the nature of the studied sample limits the external generalizability of the results, it may offer guidance for future interventions in clearly delineated settings.
Comparative metabolome analysis reveals higher potential of haemoperfusion adsorption in providing favourable outcome in ACLF patients
Authors: Yadav Manisha , Maiwal Rakhi , Kumar BR Vinay , Tripathi Gaurav , Sharma Neha , Sharma Nupur , Bindal Vasundhra , Mathew Babu , Pandey Sushmita , Singh Satender Pal , Tevathia Harsh Vardhan , Maras Jaswinder Singh , Sarin Shiv Kumar
Published: February 2024

Background and Aims

Acute‐on‐chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed.

Methods

We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post‐HA and TPE sessions on days 7 and 14 using high‐resolution mass spectrometry.

Results

The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p < .05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine‐proline metabolism (6 metabolites) and microbial metabolism respectively (p < .05). Metabolites linked to taurine‐hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post‐TPE therapy (p < .05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post‐HA therapy compared to TPE and SMT (p < .05). Higher baseline plasma level of 11‐deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p < .05) and mortality (log‐rank‐p < .05). Notably, 51 of the 64 metabolite signatures (ACLF non‐survivor) were reversed post‐HA treatment compared to TPE and SMT(p < .05).

Conclusion

HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11‐deoxycorticosterone level correlates with early mortality in ACLF patients.
Impact of dietary ketosis on volatile anesthesia toxicity in a model of Leigh syndrome
Authors: Spencer Kira A. , Howe Miranda N. , Mulholland Michael T. , Truong Vivian , Liao Ryan W. , Chen Yihan , Setha Monyreak , Snell John C. , Hanaford Allison , James Katerina , Morgan Philip G. , Sedensky Margaret M. , Johnson Simon C.
Published: February 2024

Background

Genetic mitochondrial diseases impact over 1 in 4000 individuals, most often presenting in infancy or early childhood. Seizures are major clinical sequelae in some mitochondrial diseases including Leigh syndrome, the most common pediatric presentation of mitochondrial disease. Dietary ketosis has been used to manage seizures in mitochondrial disease patients. Mitochondrial disease patients often require surgical interventions, leading to anesthetic exposures. Anesthetics have been shown to be toxic in the setting of mitochondrial disease, but the impact of a ketogenic diet on anesthetic toxicities in this setting has not been studied.

Aims

Our aim in this study was to determine whether dietary ketosis impacts volatile anesthetic toxicities in the setting of genetic mitochondrial disease.

Methods

The impact of dietary ketosis on toxicities of volatile anesthetic exposure in mitochondrial disease was studied by exposing young Ndufs4(−/−) mice fed ketogenic or control diet to isoflurane anesthesia. Blood metabolites were measured before and at the end of exposures, and survival and weight were monitored.

Results

Compared to a regular diet, the ketogenic diet exacerbated hyperlactatemia resulting from isoflurane exposure (control vs. ketogenic diet in anesthesia mean difference 1.96 mM, Tukey's multiple comparison adjusted p = .0271) and was associated with a significant increase in mortality during and immediately after exposures (27% vs. 87.5% mortality in the control and ketogenic diet groups, respectively, during the exposure period, Fisher's exact test p = .0121). Our data indicate that dietary ketosis and volatile anesthesia interact negatively in the setting of mitochondrial disease.

Conclusions

Our findings suggest that extra caution should be taken in the anesthetic management of mitochondrial disease patients in dietary ketosis.
Rules as data
Authors: Damonte Alessia , Bazzan Giulia
Published: February 2024

Rules lie at the core of many disciplines beneath regulatory studies. Such a broad interest inevitably comes with fragmented understandings and technical choices that hinder knowledge cumulation and learning. This introduction tackles these limitations through an encompassing analytical blueprint from measurement theory. First, it addresses ambiguities to establish formal rules as a distinct research object. Then, it builds on legal, institutional analytic, and computational linguistic frameworks to pinpoint their constituting elements. Last, it revises strategies for assigning meaningful numbers to objects and outlines how the contributions to this Special Issue foster different aspects of the blueprint.
Seeking information about waste‐to‐energy incineration projects: The role of objective knowledge and benefit perceptions in an extended PRISM
Authors: Zeng Jing , Duan Hongyu , Zhou Zhonglin , Song Jingyan
Published: February 2024

Although waste‐to‐energy (WtE) incineration projects have boosted the economic effectiveness of the waste management system, locals frequently view them with suspicion, opposition, or even outright rejection because of potential environmental and health risks. In this study, by incorporating two additional variables, namely, objective knowledge and benefit perceptions, the planned risk information seeking model (PRISM) was extended in the context of the WtE incineration project. A total of 1726 respondents were interviewed in person. Results from the structural equation modeling indicated that the extended PRISM achieved excellent fits, suggesting the generalizability of the model in these contexts. Objective knowledge and subjective knowledge have a positive and direct impact on perceived knowledge insufficiency. The impact of benefit and risk perceptions on worry is the opposite, with risk perceptions having a greater direct effect on worry. However, compared with risk perceptions, the direct effect that benefit perceptions have on perceived knowledge insufficiency is stronger. Additionally, perceived knowledge insufficiency partially or completely mediates the relationships between all antecedents, except perceived seeking control, and information‐seeking intention. This study suggests that risk managers carefully consider how to establish powerful communication tactics to shape these antecedents when introducing a “not in my backyard” project to the local community.
Online discourse in the post‐ “new racism” era?: Toward a theory of colorblind nationalism
Authors: Brooks Marcus A.
Published: February 2024

The literature on styles of racetalk, the way we talk about race in racist social structures, suggests that racial discourse is either covertly or overtly racist, with covert racism being dominant in the offline world and overt racism remaining dominant online. In this study I ask: is there a style of racetalk found in online discourse that does not fit within the covert/overt binary of racetalk that is present in the current literature. To address this research question, I draw on data from three social media platforms, TikTok, YouTube, and Twitter, and examine two racialized popular discourses, the cancellation of Aunt Jemima and the debates over Critical Race Theory. I find that among conservative social media users, but not liberals, neither overt nor covert styles of racetalk, describe the character of the racial discourse in my data. Instead, I find a distinct style of racetalk with three characteristics: (1) Conservative social media users draw politicized boundaries which frame Black people as part of their ingroup and leftists as an outgroup, (2) The members of the political ingroup, white conservatives and Black people, share a common threat from the political outgroup, and (3) The political ingroup should represent a multiracial political coalition who supports conservative politicians and causes. I introduce Colorblind Nationalism as a theory of politicized racetalk which situates these findings within our current socio‐political context and creates avenues for future research.
Emphysematous pyometra and emphysematous hepatitis caused by Klebsiella pneumoniae infection in a diabetic dog
Authors: Palomares Anna , Espada Yvonne , Tobón Restrepo Mauricio , Abarca Maria Lourdes , Torrente Carlos , Martino Laura , Viñeta Clàudia , Roura Xavier , Novellas Rosa
Published: February 2024

A 14‐year‐old intact female diabetic dog presented with seizures and hyperglycemic hyperosmolar syndrome. Radiographs revealed gas‐filled tubular structures in the right and left caudal abdomen, raising concerns of emphysematous pyometra or small intestinal ileus. Ultrasonography played a pivotal role in confirming emphysematous pyometra, a technique previously documented only once in veterinary practice. This report also presents the first documented case of emphysematous pyometra in a diabetic dog attributed to Klebsiella pneumoniae and complicated by emphysematous hepatitis.
An exercise physiologist's guide to metabolomics
Authors: Owens Daniel J. , Bennett Samuel
Published: February 2024

The field of exercise physiology has undergone significant technological advancements since the pioneering works of exercise physiologists in the early to mid‐20th century. Historically, the ability to detect metabolites in biofluids from exercising participants was limited to single‐metabolite analyses. However, the rise of metabolomics, a discipline focused on the comprehensive analysis of metabolites within a biological system, has facilitated a more intricate understanding of metabolic pathways and networks in exercise. This review explores some of the pivotal technological and bioinformatic advancements that have propelled metabolomics to the forefront of exercise physiology research. Metabolomics offers a unique ‘fingerprint’ of cellular activity, offering a broader spectrum than traditional single‐metabolite assays. Techniques, including mass spectrometry and nuclear magnetic resonance spectroscopy, have significantly improved the speed and sensitivity of metabolite analysis. Nonetheless, challenges persist, including study design and data interpretation issues. This review aims to serve as a guide for exercise physiologists to facilitate better research design, data analysis and interpretation within metabolomics. The potential of metabolomics in bridging the gap between genotype and phenotype is emphasised, underscoring the critical importance of careful study design and the selection of appropriate metabolomics techniques. Furthermore, the paper highlights the need to deeply understand the broader scientific context to discern meaningful metabolic changes. The emerging field of fluxomics, which seeks to quantify metabolic reaction rates, is also introduced as a promising avenue for future research.
Superionic lithium transport via multiple coordination environments defined by two-anion packing
Authors: Han Guopeng , Vasylenko Andrij , Daniels Luke M. , Collins Chris M. , Corti Lucia , Chen Ruiyong , Niu Hongjun , Manning Troy D. , Antypov Dmytro , Dyer Matthew S. , Lim Jungwoo , Zanella Marco , Sonni Manel , Bahri Mounib , Jo Hongil , Dang Yun , Robertson Craig M. , Blanc Frédéric , Hardwick Laurence J. , Browning Nigel D. , Claridge John B. , Rosseinsky Matthew J.
Published: February 2024

Fast cation transport in solids underpins energy storage. Materials design has focused on structures that can define transport pathways with minimal cation coordination change, restricting attention to a small part of chemical space. Motivated by the greater structural diversity of binary intermetallics than that of the metallic elements, we used two anions to build a pathway for three-dimensional superionic lithium ion conductivity that exploits multiple cation coordination environments. Li7Si2S7I is a pure lithium ion conductor created by an ordering of sulphide and iodide that combines elements of hexagonal and cubic close-packing analogously to the structure of NiZr. The resulting diverse network of lithium positions with distinct geometries and anion coordination chemistries affords low barriers to transport, opening a large structural space for high cation conductivity.
Accelerated photochemical reactions at oil-water interface exploiting melting point depression
Authors: Tian Ya-Ming , Silva Wagner , Gschwind Ruth M. , König Burkhard
Published: February 2024

Water can accelerate a variety of organic reactions far beyond the rates observed in classical organic solvents. However, using pure water as a solvent introduces solubility constraints that have limited the applicability of efficient photochemistry in particular. We report here the formation of aggregates between pairs of arenes, heteroarenes, enamines, or esters with different electron affinities in an aqueous medium, leading to an oil-water phase boundary through substrate melting point depression. The active hydrogen atoms in the reactants engage in hydrogen bonds with water, thereby accelerating photochemical reactions. This methodology realizes appealingly simple conditions for aqueous coupling reactions of complex solid molecules, including complex drug molecules that are poorly soluble in water.
Bacterial nucleoid is a riddle wrapped in a mystery inside an enigma
Authors: Kuzminov Andrei
Published: February 2024

Bacterial chromosome, the nucleoid, is traditionally modeled as a rosette of DNA mega-loops, organized around proteinaceous central scaffold by nucleoid-associated proteins (NAPs), and mixed with the cytoplasm by transcription and translation. Electron microscopy of fixed cells confirms dispersal of the cloud-like nucleoid within the ribosome-filled cytoplasm. Here, I discuss evidence that the nucleoid in live cells forms DNA phase separate from riboprotein phase, the “riboid.” I argue that the nucleoid-riboid interphase, where DNA interacts with NAPs, transcribing RNA polymerases, nascent transcripts, and ssRNA chaperones, forms the transcription zone. An active part of phase separation, transcription zone enforces segregation of the centrally positioned information phase (the nucleoid) from the surrounding action phase (the riboid), where translation happens, protein accumulates, and metabolism occurs. I speculate that HU NAP mostly tiles up the nucleoid periphery—facilitating DNA mobility but also supporting transcription in the interphase. Besides extruding plectonemically supercoiled DNA mega-loops, condensins could compact them into solenoids of uniform rings, while HU could support rigidity and rotation of these DNA rings. The two-phase cytoplasm arrangement allows the bacterial cell to organize the central dogma activities, where (from the cell center to its periphery) DNA replicates and segregates, DNA is transcribed, nascent mRNA is handed over to ribosomes, mRNA is translated into proteins, and finally, the used mRNA is recycled into nucleotides at the inner membrane. The resulting information-action conveyor, with one activity naturally leading to the next one, explains the efficiency of prokaryotic cell design—even though its main intracellular transportation mode is free diffusion.
Cutis verticis gyrata associated with congenital heart disease
Authors: Teresa-Palacio Marta , Akpoke Michael Agwu , Bah Abubakarr Bailor , Aldecoa-Bilbao Victoria
Published: February 2024

Cutis verticis gyrata (CVG) is a very rare benign disorder characterised by convoluted folds and deep furrows of the scalp that mimic cerebral sulci and gyri. Associations with other pathologies as neuropsychiatric and/or ophthalmologic disorders, secondary cases to inflammatory or neoplastic processes, as well as cases associated to genetic disorders as Turner’s syndrome have been reported, but there is no literature describing an association with a congenital structural heart defect and no other underlying condition. We report a case of primary CVG in a 3-week-old female infant associated with an echocardiographic diagnosis of cor triatriatum. Other systemic examination findings and investigations were unremarkable, and the patient has normal neurodevelopment at 1 year old. Aside from the neuropsychiatric and ophthalmologic pathologies commonly associated with primary non-essential CVG, it should be noted that isolated congenital cardiac lesions are also possible, so as to increase our index of suspicion in patients with the disorder.
Effect of exercise for depression: systematic review and network meta-analysis of randomised controlled trials
Authors: Noetel Michael , Sanders Taren , Gallardo-Gómez Daniel , Taylor Paul , del Pozo Cruz Borja , van den Hoek Daniel , Smith Jordan J , Mahoney John , Spathis Jemima , Moresi Mark , Pagano Rebecca , Pagano Lisa , Vasconcellos Roberta , Arnott Hugh , Varley Benjamin , Parker Philip , Biddle Stuart , Lonsdale Chris
Published: February 2024

Objective

To identify the optimal dose and modality of exercise for treating major depressive disorder, compared with psychotherapy, antidepressants, and control conditions.

Design

Systematic review and network meta-analysis.

Methods

Screening, data extraction, coding, and risk of bias assessment were performed independently and in duplicate. Bayesian arm based, multilevel network meta-analyses were performed for the primary analyses. Quality of the evidence for each arm was graded using the confidence in network meta-analysis (CINeMA) online tool.

Data sources

Cochrane Library, Medline, Embase, SPORTDiscus, and PsycINFO databases.

Eligibility criteria for selecting studies

Any randomised trial with exercise arms for participants meeting clinical cut-offs for major depression.

Results

218 unique studies with a total of 495 arms and 14 170 participants were included. Compared with active controls (eg, usual care, placebo tablet), moderate reductions in depression were found for walking or jogging (n=1210, κ=51, Hedges’ g −0.62, 95% credible interval −0.80 to −0.45), yoga (n=1047, κ=33, g −0.55, −0.73 to −0.36), strength training (n=643, κ=22, g −0.49, −0.69 to −0.29), mixed aerobic exercises (n=1286, κ=51, g −0.43, −0.61 to −0.24), and tai chi or qigong (n=343, κ=12, g −0.42, −0.65 to −0.21). The effects of exercise were proportional to the intensity prescribed. Strength training and yoga appeared to be the most acceptable modalities. Results appeared robust to publication bias, but only one study met the Cochrane criteria for low risk of bias. As a result, confidence in accordance with CINeMA was low for walking or jogging and very low for other treatments.

Conclusions

Exercise is an effective treatment for depression, with walking or jogging, yoga, and strength training more effective than other exercises, particularly when intense. Yoga and strength training were well tolerated compared with other treatments. Exercise appeared equally effective for people with and without comorbidities and with different baseline levels of depression. To mitigate expectancy effects, future studies could aim to blind participants and staff. These forms of exercise could be considered alongside psychotherapy and antidepressants as core treatments for depression.

Systematic review registration

PROSPERO CRD42018118040.
Off-pump injectable versus on-pump conventional tissue valves for pulmonary valve replacement: the injectable valve implantation randomised trial (INVITE)
Authors: Heys Rachael , Walker-Smith Terrie , Evans Rebecca , Caputo Massimo , Culliford Lucy , Reeves Barnaby , Rogers Chris , Turner Mark , Hamilton Mark , Sheehan Karen , Viola Nicola , Stoica Serban , Wright Kim , Angelini Gianni , Parry Andrew
Published: February 2024

Objectives

To assess the effectiveness of injectable tissue pulmonary valve compared with standard pulmonary valve in patients requiring pulmonary valve replacement surgery.

Design

A multicentre, single-blind, parallel two-group randomised controlled trial. Participants were blind to their allocation. Follow-up continued for 6 months. Randomised allocations were generated by a computer using block randomisation, stratified by centre.

Setting

Two National Health Service secondary care centres in the UK.

Participants

People aged 12–80 years requiring pulmonary valve replacement.

Interventions

Participants were randomly allocated (1:1 ratio) to injectable pulmonary valve replacement (IPVR) without cardiopulmonary bypass (CPB) or standard pulmonary valve replacement (SPVR) with CPB.

Primary and secondary outcome measures

The primary outcome was chest drainage volume over the first 24 hours after surgery. Secondary outcomes included in-hospital clinical outcomes; valve and heart function 6 months postsurgery and health-related quality of life 6 weeks and 6 months postsurgery.

Results

Nineteen participants agreed to take part. Eleven were allocated to IPVR and eight to SPVR. The trial was stopped before the target sample size of 60 participants was reached due to challenges in recruitment. The primary analysis includes all randomised participants; there were no withdrawals. Chest drain volume 24 hours after surgery was on average 277.6 mL lower with IPVR (IPVR mean 340.0 mL; SPVR mean 633.8 mL; mean difference, −277.6; 95% CI, −484.0 to −71.2; p=0.005). There were no statistically significant differences in time to readiness for extubation (p=0.476), time to fitness for discharge (p=0.577) and time to first discharge from the intensive care unit (p=0.209). Six participants with IPVR required CPB. Safety profiles and quality of life scores were similar.

Conclusions

IPVR reduced chest drain volume despite >50% of participants requiring CPB. There was no evidence of any other benefit of IPVR.

Trial registration number

ISRCTN23538073.
Multicentre double-blind randomised controlled trial of systematic corticosteroid therapy in patients with acute exacerbations of chronic obstructive pulmonary disease admitted to hospital with higher eosinophil levels: the ECHO protocol
Authors: Liang Lirong , Lin Yingxiang , Feng Lin , Shao Shuai , Cao Siyu , Rong Hengmo , Chu Shuilian , Xie Wuxiang , Cai Samuel , Wang Jiawen , Tong Zhaohui
Published: February 2024

Introduction

Corticosteroid is one of the most commonly used medications in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The increasing understanding of these side-effects of systematic corticosteroids and their better response to treatment among patients with COPD with higher blood eosinophil counts has led to an interest in a more targeted approach to systematic corticosteroid treatment. However, there is a lack of evidence from high-quality randomised controlled trial (RCT) studies about whether initial systematic corticosteroids should be given to patients with AECOPD with elevated eosinophilia. The aim of the present research was to test this hypothesis.

Methods and analysis

This is a multicentre, double-blind, superiority RCT in the respiratory departments of 12 general hospitals in China. It is anticipated that 456 patients with AECOPD with a blood eosinophil count >2% or >300 cells/µL at admission will be recruited. Eligible patients will be randomised (1:1) to the intervention group receiving 40 mg oral prednisone daily or identical-appearing placebo (control group) for five consecutive days. Follow-up visits are performed during hospitalisation, followed by clinic interviews on days 30, 60 and 90 after discharge. The primary outcome is treatment failure rates comprising requiring or receiving invasive or non-invasive mechanical ventilation, requiring or transferring to intensive care unit during the index hospitalisation, length of index hospitalisation longer than 14 days, death during the index hospitalisation or within 30 days after discharge and readmission with acute exacerbations of COPD within 30 days after discharge. The results of this trial will provide insight into the value of using blood eosinophil counts as a biomarker of eosinophilic exacerbation and initiating systematic corticosteroid treatment for patients with AECOPD with higher eosinophil levels.

Ethics and dissemination

This study was approved by Beijing Chaoyang Hospital Institutional Review Board (approval number: 2020-KE-544) and the main results and secondary results will be published in peer-reviewed journals.

Trial registration number

NCT05059873.
Pooling of primary care electronic health record (EHR) data on Huntington’s disease (HD) and cancer: establishing comparability of two large UK databases
Authors: Dedman Daniel , Williams Rachael , Bhaskaran Krishnan , Douglas Ian J
Published: February 2024

Objectives

To explore whether UK primary care databases arising from two different software systems can be feasibly combined, by comparing rates of Huntington’s disease (HD, which is rare) and 14 common cancers in the two databases, as well as characteristics of people with these conditions.

Design

Descriptive study.

Setting

Primary care electronic health records from Clinical Practice Research Datalink (CPRD) GOLD and CPRD Aurum databases, with linked hospital admission and death registration data.

Participants

4986 patients with HD and 1 294 819 with an incident cancer between 1990 and 2019.

Primary and secondary outcome measures

Incidence and prevalence of HD by calendar period, age group and region, and annual age-standardised incidence of 14 common cancers in each database, and in a subset of ‘overlapping’ practices which contributed to both databases. Characteristics of patients with HD or incident cancer: medical history, recent prescribing, healthcare contacts and database follow-up.

Results

Incidence and prevalence of HD were slightly higher in CPRD GOLD than CPRD Aurum, but with similar trends over time. Cancer incidence in the two databases differed between 1990 and 2000, but converged and was very similar thereafter. Participants in each database were most similar in terms of medical history (median standardised difference, MSD 0.03 (IQR 0.01–0.03)), recent prescribing (MSD 0.06 (0.03–0.10)) and demographics and general health variables (MSD 0.05 (0.01–0.09)). Larger differences were seen for healthcare contacts (MSD 0.27 (0.10–0.41)), and database follow-up (MSD 0.39 (0.19–0.56)).

Conclusions

Differences in cancer incidence trends between 1990 and 2000 may relate to use of a practice-level data quality filter (the ‘up-to-standard’ date) in CPRD GOLD only. As well as the impact of data curation methods, differences in underlying data models can make it more challenging to define exactly equivalent clinical concepts in each database. Researchers should be aware of these potential sources of variability when planning combined database studies and interpreting results.
Penicillin allergy status and its effect on antibiotic prescribing, patient outcomes and antimicrobial resistance (ALABAMA): protocol for a multicentre, parallel-arm, open-label, randomised pragmatic trial
Authors: Armitage Kelsey Fiona , Porter Catherine E , Ahmed Shadia , Cook Johanna , Boards Jenny , Bongard Emily , Butler Christopher C , Corfield Kate , Davoudianfar Mina , Galal Ushma , Howard Philip , Mujica-Mota Ruben , Saman Razan , Santillo Marta , Savic Sinisa , Shinkins Bethany , Tonkin-Crine Sarah , Wanat Marta , West Robert M , Yu Ly-Mee , Pavitt Sue , Sandoe Jonathan A T
Published: February 2024

Introduction

Incorrect penicillin allergy records are recognised as an important barrier to the safe treatment of infection and affect an estimated 2.7 million people in England. Penicillin allergy records are associated with worse health outcome and antimicrobial resistance. The ALlergy AntiBiotics And Microbial resistAnce (ALABAMA) trial aims to determine if an intervention package, centred around a penicillin allergy assessment pathway (PAAP) initiated in primary care, is safe and effective in improving patient health outcomes and antibiotic prescribing.

Methods and analysis

The ALABAMA trial is a multicentre, parallel-arm, open-label, randomised pragmatic trial with a nested pilot study. Adults (≥18 years) with a penicillin allergy record and who have received antibiotics in the previous 24 months will be eligible for participation. Between 1592 and 2090 participants will be recruited from participating National Health Service general practices in England. Participants will be randomised to either usual care or intervention to undergo a pre-emptive PAAP using a 1:1 allocation ratio. The primary outcome measure is the percentage of treatment response failures within 28 days of an index prescription. 2090 and 1592 participants are estimated to provide 90% and 80% power, respectively, to detect a clinically important absolute difference of 7.9% in primary outcome at 1 year between groups. The trial includes a mixed-methods process evaluation and cost-effectiveness evaluation.

Ethics and dissemination

This trial has been approved by London Bridge Research Ethics Committee (ref: 19/LO/0176). It will be conducted in compliance with Good Clinical Practice guidelines according to the Declaration of Helsinki. Informed consent will be obtained from all subjects involved in the study. The primary trial results will be submitted for publication to an international, peer-reviewed journal.

Trial registration

ISRCTN20579216.
Evaluation of an integrated care pathway for out-of-hospital treatment of older adults with an acute moderate-to-severe lower respiratory tract infection or pneumonia: protocol of a mixed methods study
Authors: Roos Rick , Pepping Rianne M C , van Aken Maarten O , Labots Geert , Lahdidioui Ali , van den Berg Johanna M W , Kolfschoten Nikki E , Pasha Sharif M , ten Holder Joris T , Mollink Susan M , van den Bos Frederiek , Kant Jojanneke , Kroon Ingrid , Vos Rimke C , Numans Mattijs E , van Nieuwkoop Cees
Published: February 2024

Introduction

Older adults with an acute moderate-to-severe lower respiratory tract infection (LRTI) or pneumonia are generally treated in hospitals causing risk of iatrogenic harm such as functional decline and delirium. These hospitalisations are often a consequence of poor collaboration between regional care partners, the lack of (acute) diagnostic and treatment possibilities in primary care, and the presence of financial barriers. We will evaluate the implementation of an integrated regional care pathway (‘The Hague RTI Care Bridge’) developed with the aim to treat and coordinate care for these patients outside the hospital.

Methods and analysis

This is a prospective mixed methods study. Participants will be older adults (age≥65 years) with an acute moderate-to-severe LRTI or pneumonia treated outside the hospital (care pathway group) versus those treated in the hospital (control group). In addition, patients, their informal caregivers and treating physicians will be asked about their experiences with the care pathway. The primary outcome of this study will be the feasibility of the care pathway, which is defined as the percentage of patients treated outside the hospital, according to the care pathway, whom fully complete their treatment without the need for hospitalisation within 30 days of follow-up. Secondary outcomes include the safety of the care pathway (30-day mortality and occurrence of complications (readmissions, delirium, falls) within 30 days); the satisfaction, usability and acceptance of the care pathway; the total number of days of bedridden status or hospitalisation; sleep quantity and quality; functional outcomes and quality of life.

Ethics and dissemination

The Medical Research Ethics Committee Leiden The Hague Delft (reference number N22.078) has confirmed that the Medical Research Involving Human Subjects Act does not apply to this study. The results will be published in international peer-reviewed journals.

Trial registration number

ISRCTN68786381.
Integrating 4 methods to evaluate physical function in patients with cancer (In4M): protocol for a prospective cohort study
Authors: Thanarajasingam Gita , Kluetz Paul , Bhatnagar Vishal , Brown Abbie , Cathcart-Rake Elizabeth , Diamond Matthew , Faust Louis , Fiero Mallorie H , Huntington Scott , Jeffery Molly Moore , Jones Lee , Noble Brie , Paludo Jonas , Powers Brad , Ross Joseph S , Ritchie Jessica D , Ruddy Kathryn , Schellhorn Sarah , Tarver Michelle , Dueck Amylou C , Gross Cary
Published: February 2024

Introduction

Accurate, patient-centred evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterise the longitudinal measurement characteristics of physical function assessments, including clinician-reported outcome, patient-reported ported outcome (PRO), performance outcome tests and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice.

Methods and analysis

In this prospective study, we are enrolling 200 English-speaking and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centred health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multimodal physical function data collection in real-world patients with breast cancer or lymphoma will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform and PROs.

Ethics and dissemination

This study has received approval from IRBs at Mayo Clinic, Yale University and the US Food and Drug Administration. Results will be made available to participants, funders, the research community and the public.

Trial registration number

NCT05214144; Pre-results.
Assessment of oxygen extraction rate changes following red blood cell transfusion in the intensive care unit: a protocol for a prospective observational non-interventional study
Authors: Tüzen Ahmet Salih , Aksun Murat , Sencan Atilla , Girgin Senem , Gölboyu Birzat Emre , Kırbaş Gizem , Şanlı Ozan
Published: February 2024

Introduction

Haemoglobin transfusion thresholds have been used in the intensive care unit (ICU) to guide red blood cell transfusion (RBCT) decisions. Recent research has also focused on physiological indicators of tissue oxygenation as trigger points for blood transfusion. This study aims to assess the oxygen extraction rate (O2ER) as a critical indicator of the oxygen delivery–consumption balance in tissues and investigate its potential as a reliable trigger for blood transfusion in ICU patients by analysing clinical outcomes. The utilisation of physiological indicators may expedite the decision-making process for RBCT in patients requiring immediate intervention, while simultaneously minimising the risks associated with unnecessary transfusions.

Methods and analysis

This prospective, single-centre, observational cohort study will include 65 ICU patients undergoing RBCT. We will evaluate essential markers such as arterial oxygen content, central venous oxygen content, arteriovenous oxygen difference, O2ER and near-infrared spectroscopy before and 15 min after transfusion. The primary outcome is the percentage increase in O2ER between the two groups relative to the initial O2ER level. Secondary outcomes will assess complications and patient outcomes in relation to baseline O2ER. A 90-day comprehensive follow-up period will be implemented for all enrolled patients.

Ethics and dissemination

This study has obtained ethics committee approval from the Izmir Katip Celebi University Non-Interventional Clinical Studies Institutional Review Board. Written informed consent will be obtained from all patients before their enrolment in the study. The findings will be disseminated through publication in peer-reviewed journals and presentation at national or international conferences.

Trial registration number

NCT05798130