bluuebunny/crossref_metadata_2025 huggingface dataset:
Navigating online health information: Insights into consumer influence and decision-making strategies—An overview of reviews
Authors: Crespo-Gonzalez Carmen , Benrimoj Shalom I , Frommer Michael , Dineen-Griffin Sarah
Published: October 2024

Objective

Communities' use of technology and the internet for online health information (OHI) is increasing exponentially. An understanding of how and why individuals access OHI, and how this information influences decisions on health, medicines and self-care practices is critical. This review aims to: (1) identify the factors influencing OHI-seeking behaviour; (2) evaluate the evidence of OHI on self-care practices; and (3) outline strategies to improve online informed decision-making and assess the impact of these strategies on consumer outcomes.

Methods

A review of systematic reviews was conducted in November of 2023, following the Cochrane Handbook and PRISMA guidelines, and using PubMed, Scopus, Web of Science and EBSCOhost databases. The methodological quality of retrieved reviews was appraised using the AMSTAR 2 tool.

Results

The search retrieved 1725 records. Of these, 943 were screened, and 33 were included in the final analysis. The most frequently identified reasons for seeking OHI were to retrieve diagnostic and treatment information, and well-being and emotional support. Level of education and socio-economic status influenced OHI-seeking. OHI directly influenced self-care decision-making by individuals and their relationships and communication with healthcare providers. Overall, OHI-seeking (and interventions to promote the use of OHI) enhanced individuals’ confidence, skills and knowledge.

Conclusions

The findings highlight the benefits of OHI-seeking and its potential influence on self-care decisions. Future research should focus on strategies that would promote the pursuit of high-quality, up-to-date OHI and on the development of interventions for healthcare professionals to improve patients’ use of OHI in self-care and self-efficacy.
The Danish Goldsmiths Musical Sophistication Index: Validation in Samples with Different Degrees of Representativeness
Authors: Møller Cecilie , Hansen Niels Chr. , Vuust Peter , Müllensiefen Daniel
Published: October 2024

Convenience sampling is often used in music psychology research, leading to an overrepresentation of young participants with high socio-economic status and potentially compromising the generalizability of empirical findings to the broader population. Fortunately, analysis techniques enable matching biased samples to known population characteristics, for example, age, gender, and employment status. This study’s aim is twofold. First, we validate the Danish version of the Goldsmiths Musical Sophistication Index (Gold-MSI-da), a self-report inventory assessing various aspects of musical sophistication on continuous scales in the general population. Then, we demonstrate the use of stratification techniques and quantify the influence of sample composition by comparing results from analyses performed on our biased sample to similar analyses performed using stratified subsampling and poststratification weights to increase representativeness. The bifactor structure of the Gold-MSI-da was consistently replicated, showing similar subscale percentiles in three sample variants. Psychometric benchmarks of internal consistency aligned with benchmarks from other language versions, and although model fits were weaker in the most representative sample, they were still acceptable. Interestingly, the sizes of the effect of self-reported musical training and expertise on musical listening abilities diminished with increasing sample representativeness, indicating potential overestimation when relying on non-representative samples. We conclude that the Gold-MSI-da is a valid tool for assessing musical sophistication in the Danish general population.
Moderators of the Effect of Household Food Insecurity on Food Consumption Among Uruguayan Children and Adolescents
Authors: Brunet Gerónimo , Girona Alejandra , Fajardo Gabriela , Ares Gastón
Published: October 2024

The aims of the present work were to examine the effect of food insecurity on food consumption among children/adolescents in Uruguay and to explore the moderating effect of socio-economic and demographic characteristics. The design consisted of an analysis of secondary data from a telephone survey ( n = 1,504), applied to parents or tutors of children and adolescents living in Uruguay (September–October, 2020). Data were analyzed using logistic regression models and moderation analyses were run considering household socioeconomic and demographic characteristics. Food insecurity reduced the likelihood of having consumed all food groups except for carbohydrate-based foods, whereas it increased the likelihood of consuming pulses. Age of the child/adolescent, being beneficiary of income transfers and state-provided food baskets significantly moderated the effect of food insecurity on the consumption of several food groups. Results suggest that a combination of cash transfers, subsidies and marketing restrictions hold potential to reduce food insecurity and its negative effects on diet.
Research on Green Innovation Spillover Effects of Peers Issuing Green Bonds: Evidence from China’s Green Bond Market
Authors: Wang Qiankun , Chen Mingsheng , Liu Tingwen
Published: October 2024

Green innovation plays a crucial role in fostering economic growth alongside environmental preservation. This study investigates the relationship between the issuance of green bonds and green innovation among peer companies, utilizing green patent data. The findings reveal that the issuance of green bonds significantly bolsters the level of green innovation among peer companies. Strategic innovation appears to be more pronounced than substantive innovation. The mechanism analysis indicates that the issuance of green bonds influences peer companies to engage in green innovation activities by alleviating their financing constraints and increasing their level of R&D investment. The heterogeneity analysis reveals that the impact of green bond issuance on green innovation among peer companies is particularly pronounced in capital-intensive companies and industries with high concentration. This study not only contributes evidence to the theory of “peer learning” but also provides a theoretical basis for expanding the economic benefits associated with green finance.
Linking New Ways of Working to Employee Performance in Emerging Countries: The Interplay of Technostress, and Meaningful Work
Authors: Nguyen Phuong Ngoc-Duy , Nguyen Huan Hong , Giang Trang Thi , Duong Hiep Cong , Nguyen Linh Duy-Yen
Published: October 2024

The COVID-19 pandemic has significantly reshaped the landscape of work, prompting an urgent inquiry into the new ways of working among scholars and industry practitioners. Amidst this global transformation, Vietnam stands out as a developing nation embracing remote and hybrid working models, yet there is a notable gap in empirical research. This study aims to provide valuable insights into the intricate interplay between new ways of working (NWOW), meaningful work (MW), technostress (TNS), and perceived job performance (JP) in the context of an emerging economy. The study adopted a cross-sectional quantitative approach, utilizing a questionnaire administered through online platforms to a diverse group of professional participants in Vietnam. Convenience sampling was used to gather data. Upon completion of data collection, a total of 309 valid observations were obtained, ensuring an extensive representation of the research phenomenon within its distinct sociocultural context. The analysis was conducted using partial least squares structural equation modeling (PLS-SEM), a method well-suited for robust testing of hypotheses. This study shows a positive correlation between NWOW and both TNS and JP. However, the negative relationship between TNS and JP was not statistically supported. On the other hand, the study confirmed a strong positive relationship between NWOW and perceived MW, which also significantly impacted JP. The study provides actionable insights for organizations planning to implement or enhance NWOW, stressing the importance of understanding its complex impacts on MW and TNS. This study significantly contributes to the literature by exploring the intricate relationships among NWOW, TNS, MW, and JP in an emerging economic context, providing a nuanced understanding of these dynamics.
Intolerance of Uncertainty Worsens Career Indecisiveness and Anxiety Among Chinese NEET During the COVID-19 Pandemic: Mediation Roles of Memes Use and Depression Emoticon Empathy
Authors: Tang Yulun , Zhang Sensen , Wu Fan , Yang Liheng
Published: October 2024

The term “NEET” refers to individuals aged 15 to 34 years who are not involved in education, employment, or training programs. Recent studies have shown that NEET individuals are at a high risk of experiencing lower well-being and mental health issues. This study aimed to examine the relationship between intolerance of uncertainty (IU), meme use (MU), depression emoticon empathy (DEE), and career indecisiveness and anxiety (CIA) in NEETs who were locked down during the COVID-19 pandemic in China. We hypothesize positive interrelations among study variables. Then, mediation path models were carried out to study the relationship between IU and CIA through MU and DEE. We collected data through an online survey from NEETs (N = 1,404) in China, using questionnaires assessing IU, MU, DEE, and CIA, and Structural Equation Modeling analyses were performed to explore the interrelations among them. We found that IU influenced NEET’s CIA primarily through the independent intermediaries of MU and DEE. Additionally, the chain intermediary of MU → DEE was significant. Our study indicated that MU and DEE partially mediated the relationship between IU and CIA, respectively. Digital communications through MU and DEE are playing an important role in the relationship between IU and CIA, respectively. Therefore, MU and DEE as studied in this research may work as alarm to foretell early of the CIA among NEET. Moreover, our findings could be used as a reference for promoting employment and increasing the employment rate among NEET population and might be a potential target for intervention or service delivery.
Transformational Leadership and Climate of Trust: Mediating Role of Organizational Justice
Authors: Akter Kaniz Marium , Banik Subrata , Tang Swee Mei , Adnan Zurina
Published: October 2024

Despite universal agreement on the consequences of the organizational trust climate, little attention has been given to studying its determinants. This study aimed to investigate the role of managers’ transformational leadership behavior in developing trust climate in the hotel industry. Based on the social exchange theory, this study also examined the mediation effect of organizational justice in the relationship between managers’ transformational leadership and trust climate. Data were collected from 323 full-time employees engaged in three-star Bangladeshi hotels. The study employed a PLS-SEM approach to test the hypotheses. Results exposed the significant impact of managers’ transformational leadership on the hotels’ trust climate, and organizational justice mediates the aforementioned relationship. These findings highlight the role of managerial transformational leadership and organizational justice in developing and nurturing a climate of trust. Based on the results, the study offers theoretical and practical implications, along with further research directions.
A Computer Vision System for an Automated Scoring of a Hand-drawn Geometric Figure
Authors: Wahyuningrum Shinta Estri , van Luijtelaar Gilles , Sulastri Augustina , Hendriks Marc P.H. , Sanjaya Ridwan , Heskes Tom
Published: October 2024

Visual Reproduction is a condition to measure Visual Spatial Memory as one of the cognitive domains commonly used to measure visuo-spatial memory. Geometric figures serve as stimulus material, and probands have to reproduce the figures from memory through a hand drawing. The scoring of the drawing has subjective elements. This study aims to evaluate the scoring criteria for the Figural Reproduction Test (FRT), part of the Indonesian Neuropsychological Test Battery, and to develop and evaluate an automated scoring system based on computer vision technology (FRT-CVAS). Scoring evaluation conducted by Cohen Kappa analysis, accuracy, sensitivity, and specificity. The analyzes of the three criteria of the manual confirmed a subjective element in the scoring of the shape of triangles by a moderate (0.74) inter-rater agreement; this agreement could be improved to 0.84 by a slight modification of its criteria. FRT-CVAS, based on computer vision’s identification of the different elements of the hand drawing, was developed and trained using 290 drawings. The system was additionally tested by comparing its scoring with the scoring of two independent raters on 120 drawings from a second data set. FRT-CVAS recognized all elements, and its comparison between human raters showed a high accuracy and sensitivity (minimally 0.91), while the specificity was 0.80 for one of the three criteria. FRT-CVAS offers a highly standardized, consistent, precise, and objective output from the first card in the FRT. This approach is advantageous to data-hungry alternatives such as deep learning when applied to the automated scoring of hand drawings with relatively little data available for training.
The Relationship Between Entrepreneurial Alertness, Firm’s Outcomes, and SME-Specific Factors
Authors: Yamauchi Nao , Ichikohji Takeyasu , Sato Hidenori
Published: October 2024

This study focuses on the cognitive abilities of managers and examines the effect of entrepreneurial alertness (EA) of small and medium-sized enterprise (SME) managers on the quality of strategic decision-making and firm performance under uncertain environmental conditions. This study also sheds light on the antecedents of EA that are crucial for SMEs by focusing on the nuances of socio-emotional wealth (SEW) arising from business succession. The results of structural equation modeling based on a questionnaire survey of SMEs in Japan, where the society is aging rapidly and the business succession situation is becoming more serious, show that EA is positively related to the quality of strategic decision-making and firm performance. However, managers’ intrafamilial business succession attributes affect EA negatively and are positively moderated when social capital is formed within families. These findings contribute to the theoretical development of EA by extending the scope of study. Additionally, the findings provide a practical perspective by clarifying the nuances of business succession, which can be problematic for many firms.
Hepatitis B and C Virus Co-Infection and Their Association With Liver Disease in Persons With HIV in Nigeria
Authors: Odeghe Emuobor , Oyeleke Ganiyat , Odofin Mayowa , Duguru Mary , Davwar Pantong , Nyam David , Lesi Olufunmilayo , Okeke Edith , Adelabu Hameed , Odukoya Oluwakemi , Akanmu Alani , Adeyemo Wasiu , Abdulkareem Fatimah , Imade Godwin , Joyce Brian , Khan Imran , Chandler Ariel , Sagay Atiene , Murphy Robert , Hou Lifang , Hawkins Claudia
Published: October 2024

Background: The burden of chronic viral hepatitis among people living with human immunodeficiency virus (PLWH) and its association with liver disease in Nigeria has been seldom explored. Our objective was to compare characteristics in PLWH with and without significant liver fibrosis/cirrhosis, examining its association with viral hepatitis and other risk factors. Methods: Cross-sectional study among PLWH with and without significant fibrosis/cirrhosis (transient elastography ≥ 9.3 kPa) between July 2018 and August 2022. Data were compared between participant groups and logistic regression used to determine association between chronic viral hepatitis and significant fibrosis/cirrhosis. Results: Five hundred and thirty-seven participants (34.3% male), median age 46 years, 22.2% with significant fibrosis/cirrhosis were analyzed. Seroprevalence of hepatitis B virus (HBV) was 11.2% and hepatitis C virus (HCV) 5.7%. Male sex, diabetes, HBV, and HCV were associated with significant fibrosis/cirrhosis, while ART for >5 years was associated with reduced risk. Conclusion: The chronic hepatitis viruses are associated with significant liver fibrosis/cirrhosis in PLWH in Nigeria, highlighting the importance of viral hepatitis awareness, screening, and treatment in HIV programs to reduce the risk of liver disease.

Plain Language Summary

Hepatitis B and C infection and liver disease in people with HIV infection in Nigeria People living with human immunodeficiency virus (HIV) infection who have hepatitis B or C infection have a higher chance of developing advanced liver disease than those who do not have either of the hepatitis infections. This finding highlights the importance of awareness, screening, and treatment of the hepatitis viruses in HIV programs in order to reduce the risk of liver disease in this population.
Sound Localization in Single-Sided Deafness; Outcomes of a Randomized Controlled Trial on the Comparison Between Cochlear Implantation, Bone Conduction Devices, and Contralateral Routing of Signals Hearing Aids
Authors: van Heteren Jan A. A. , van Oorschot Hanneke D. , Wendrich Anne W. , Peters Jeroen P. M. , Rhebergen Koenraad S. , Grolman Wilko , Stokroos Robert J. , Smit Adriana L.
Published: October 2024

There is currently a lack of prospective studies comparing multiple treatment options for single-sided deafness (SSD) in terms of long-term sound localization outcomes. This randomized controlled trial (RCT) aims to compare the objective and subjective sound localization abilities of SSD patients treated with a cochlear implant (CI), a bone conduction device (BCD), a contralateral routing of signals (CROS) hearing aid, or no treatment after two years of follow-up. About 120 eligible patients were randomized to cochlear implantation or to a trial period with first a BCD on a headband, then a CROS (or vice versa). After the trial periods, participants opted for a surgically implanted BCD, a CROS, or no treatment. Sound localization accuracy (in three configurations, calculated as percentage correct and root-mean squared error in degrees) and subjective spatial hearing (subscale of the Speech, Spatial and Qualities of hearing (SSQ) questionnaire) were assessed at baseline and after 24 months of follow-up. At the start of follow-up, 28 participants were implanted with a CI, 25 with a BCD, 34 chose a CROS, and 26 opted for no treatment. Participants in the CI group showed better sound localization accuracy and subjective spatial hearing compared to participants in the BCD, CROS, and no-treatment groups at 24 months. Participants in the CI and CROS groups showed improved subjective spatial hearing at 24 months compared to baseline. To conclude, CI outperformed the BCD, CROS, and no-treatment groups in terms of sound localization accuracy and subjective spatial hearing in SSD patients.

TRIAL REGISTRATION Netherlands Trial Register ( https://onderzoekmetmensen.nl ): NL4457, CINGLE trial.
Prehospital Patient and Family Aftercare Service in Helicopter Emergency Medical Services: A Patient's Perspective
Authors: Rolfe Chris , Plumbley Stuart , Taneja Sarita , Griggs Joanne ,   On behalf of Air Ambulance Charity Kent Surrey Sussex
Published: October 2024

Over the past decade the medical profession has witnessed patient and family aftercare becoming increasingly rooted within a patient-centric approach. Furthermore, there has been strong consensus within the Helicopter Emergency Medical Service (HEMS) sector for a Patient and Family Aftercare Service (PFAS) at Air Ambulance Charity Kent Surrey Sussex to further support an individual's experience from their core primary retrieval, through to the rehabilitation experience. This patient narrative highlights key interconnections between HEMS and an aftercare team that are important to the patient experience. Firstly, the clinical team provide prompt and expert medical intervention, which is crucial in managing critical injury and illness at the scene of an injury. Secondly, the narrative explores the emotional support provided by the healthcare professionals. Thirdly, the role of the support network, comprising of family, friends, and the wider community is discussed as integral for both physical and emotional rehabilitation post-incident. Furthermore, the narrative highlights that ongoing engagement from PFAS is important to continued rehabilitation and enhanced quality of life.
Gaining Insights Into Patients’ Experiences of Remote Diagnostic Screening for Chronic Kidney Disease in Patients With Diabetes
Authors: Deaney Carl , Reesby Danielle
Published: October 2024

Introduction: Chronic kidney disease (CKD) affects a significant portion of the UK population and is a pressing public health issue. Current screening methods have a low patient uptake rate. This retrospective study explores the patient experience of remote diagnostic screening. Objective: This article retrospectively analyses patient-reported experiences, focusing on at-home urinary screening to detect CKD. Intervention: Our primary care network commissioned a remote diagnostic service for adult patients with diabetes (Types I and II) who had not taken urinary albumin: creatinine ratio test within 12 months. Patients were provided with an at-home kit and guided by a smartphone application. Qualitative clinical data was collected during screening, with a questionnaire capturing patients’ experiences. Impact: A total of 60% of eligible patients performed testing, and 35% were detected to have abnormal results. A total of 80% of patients preferred remote screening. Conclusions: This study provides evidence for remote CKD screening and opens avenues for innovation. Most patients reported a positive experience, underscoring the potential of this approach to improve health outcomes, especially in higher-risk populations.
Supporting Regional Upper Limb Arthroplasty: The Impact of Establishing an Upper Limb Orthopaedic Network
Authors: Oakley Ben , Marson Ben , Wijeratna Malin , Manning Paul , Geoghegan John , Gooding Ben
Published: October 2024

Background and Objectives

The management of complex upper limb arthroplasty has received national guidelines supporting the use of a regional network. An upper limb network was established for both elbow and shoulder arthroplasty. This study evaluates the impact of establishing this network over a 5-year period.

Methods

Data were collected from network meetings from June 2017 to December 2022. Hospital-level National Joint Registry data were obtained for analysis of case volume.

Results

A total of 243 cases were discussed. Network discussion changed the management plan in 53% of cases. Only 8% of cases required transfer to the tertiary center. The proportional caseload at either hub or spoke hospitals did not change after creation of the network.

Discussion

Regional network discussion aids decision-making for complex cases, with further management options realized in over half of the cases presented. The discussion allowed every patient to gain the advantage of regional expertise while being managed conveniently at their local hospital.
Why now? Questioning the confidence in eco-political experimentation in civil society
Authors: Dannemann Hauke , Haderer Margaret , Blühdorn Ingolfur
Published: October 2024

In the social sciences literature, experimentation in civil society as in food co-ops, urban gardens, repair cafés, or sharing platforms is widely considered as promising to address mounting socio-ecological problems. But is this confidence justified at a point in time when fundamental change is more urgent than ever? After all, these forms of experimentation have a history that reaches back to the very beginnings of environmentalism. Why should they trigger a comprehensive socio-ecological transformation today, if they have not done so in the past? For academic confidence in transformative change through experimentation to be plausible, at least one of two conditions would have to be fulfilled: either academic accounts plausibly demonstrate that the meanings and functions of present experiments fundamentally differ from those in the past. Or these accounts convincingly show that societal context conditions today are much more favourable for transformative change through experimentation than in the past. To assess whether or to what extent at least one of these conditions is fulfilled, we pursue a comparative analysis of past and present discourses on eco-political experimentation in civil society and a conjunctural analysis of current context conditions for transformative change through experimentation. Our findings suggest that neither the criterion of substantial difference nor that of favourable context conditions is fulfilled. For this reason, the current academic trust in transformative change through experimentation, arguably, remains implausible. Hence, we caution against spreading hope when doubt seems in order, for unwarranted narratives of hope may come with an unintended side-effect: ‘sustaining the unsustainable.'
Riskscapes: A framework for risk assessment in colonial contexts
Authors: Proulx Guillaume , Asselin Hugo
Published: October 2024

Risk assessment is a critical aspect of coping with environmental changes. The identification of values at risk — entities, attributes, and ideas that are important to a community — is a key component of a population's ability to resist or adapt to hazards. In colonial contexts, risk assessment must take into account the distinct relationality to the land of Indigenous and non-Indigenous groups and the historicized power relations. Most risk assessment frameworks ignore or oversimplify the cultural heterogeneity of human–environment relationships by using generalized value concepts. The few context-dependent frameworks that have been proposed do not account for different sociocultural groups living on the same land. We propose a spatial-based risk assessment approach inspired by the concept of riskscape, acknowledging diverse perceptions of risk and landscape among different sociocultural groups. We present a risk assessment method eliciting values for different sociocultural groups in their specific contexts using separate valuation methods, and then aggregating them into a joint geospatial interface to highlight convergent and competing interests. Illustrated with the boreal region of northwestern Quebec (Canada), we discuss how the riskscape framework balances Indigenous and non-Indigenous perspectives in a non-hierarchical assessment of values at risk.
Making the energy connection: A review of the geographies of high-voltage transmission
Authors: Kroot Maddy
Published: October 2024

Energy is a resurgent topic in geography and cognate fields, but its theoretical development and empirical exploration have been uneven. I argue that centering transmission as an analytical lens — rather than treating it as incidental to extraction, generation, and consumption — brings the multi-scalar spatial politics of energy systems into the foreground through attention to circulation. This article reviews work on transmission from energy geographies, science and technology studies, and the histories of energy, technology, and the environment, identifying four main themes. First, transmission is used as a lens to examine larger energy metabolisms and how the circulation of electricity entrenches spatial relations. Second, transmission is an instrument of state territorialization, both within and across borders. Third, transmission, as a particular form of electricity capital, is subject to specific regimes of accumulation and regulation. Finally, transmission lines can become objects of social contestation that entangle multi-scalar politics of energy transition, electrification, and development. The article concludes by identifying areas for further research — empirical, theoretical, and policy-oriented — through which scholarly attention to transmission can inform energy geographies, energy studies, and human-environment geography more broadly.
Paraplatforms
Authors: Steinberg Marc
Published: October 2024

In this short commentary, I suggest the term “paraplatform” as a means of expanding the purview of platform studies. The hope is that this conceptual term may open different analytic routes to platform histories and geographies; different formations of the platform society; different objects; and different lineages informing platforms and platform capitalism.
Evaluating the impact of uncertainty in ground motion forecasts for post-earthquake impact modeling applications
Authors: Engler Davis T , Jaiswal Kishor S , Ganesh Mahadevan
Published: October 2024

The US Geological Survey’s (USGS) ShakeMap system provides a rapid characterization of strong ground shaking in areas directly affected by an earthquake. This study focuses on studying the aggregate effects of macroseismic shaking estimates from ShakeMap, expressed in terms of modified Mercalli intensity (MMI), when accounting for the uncertainty in forecasted ground motions. We use a Monte Carlo approach to generate numerous spatially correlated realizations of ground motions by utilizing a combination of circulant embedding and kriging techniques for efficiently handling the correlations. We then assessed the aggregate effects of shaking by looking at bin counts across these realizations. We demonstrate that the aggregate shaking regarding the mean macroseismic intensity estimates (from the ShakeMap output) is a biased representation of the aggregate shaking when shaking uncertainty is included. Incorporating shaking uncertainty can help to improve various downstream earthquake impact applications, such as the USGS Prompt Assessment of Global Earthquakes for Response (PAGER) overall earthquake fatality distribution or estimates of shaking-induced ground failure impacts from consequential earthquakes.
Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia
Authors: Luo Meng-Xiao , Tan Tania , Trussart Marie , Poch Annika , Nguyen Thi Minh Hanh , Speed Terence P. , Hicks Damien G. , Bandala-Sanchez Esther , Peng Hongke , Chappaz Stéphane , Slade Charlotte , Utzschneider Daniel T. , Koldej Rachel M. , Ritchie David , Strasser Andreas , Thijssen Rachel , Ritchie Matthew E. , Tam Constantine S. , Lindeman Geoffrey J. , Huang David C. S. , Lew Thomas E. , Anderson Mary Ann , Roberts Andrew W. , Teh Charis E. , Gray Daniel H. D.
Published: October 2024

Venetoclax, a first-in-class BH3 mimetic drug that targets B-cell lymphoma-2 (BCL-2), has improved the outcomes of patients with chronic lymphocytic leukemia (CLL). Early measurements of the depth of the venetoclax treatment response, assessed by minimal residual disease, are strong predictors of long-term clinical outcomes. However, there are limited data on the early changes induced by venetoclax treatment that might inform strategies to improve responses. To address this gap, we conducted longitudinal mass cytometric profiling of blood cells from patients with CLL during the first 5 weeks of venetoclax monotherapy. At baseline, we resolved CLL heterogeneity at the single-cell level to define multiple subpopulations in all patients based on proliferative, metabolic, and cell survival proteins. Venetoclax induced a significant reduction in all CLL subpopulations and caused rapid upregulation of the prosurvival BCL-2, BCL-extra large, and mantle cell lymphoma-1 proteins in surviving cells, which had reduced sensitivity to the drug. In mouse models, the venetoclax-induced elevation of survival proteins in B cells and CLL-like cells that persisted was recapitulated, and genetic models demonstrated that extensive apoptosis and access to the B-cell cytokine, B-cell activating factor (BAFF), were essential. Accordingly, in patients with CLL who were treated with venetoclax or the anti-CD20 antibody obinutuzumab there was marked elevation in BAFF and an increase in prosurvival proteins in leukemic cells that persisted. Overall, these data highlight the rapid adaptation of CLL cells to targeted therapies through homeostatic factors and support cotargeting of cytokine signals to achieve deeper and more durable long-term responses.
Lymphopenia predicts poor outcomes in newly diagnosed multiple myeloma
Authors: Ferri Grace M. , Yildirim Cenk , Do Nhan V. , Brophy Mary , Park Joseph S. , Munshi Nikhil C. , Fillmore Nathanael R. , Edwards Camille V.
Published: October 2024

Bone marrow microenvironment plays an important role in promoting growth and survival of multiple myeloma (MM) cells. The tumor-promoting immune microenvironment is augmented while antitumor immune responses are inhibited. Although clinical and genomic markers of high-risk MM have been described, the immune status is just being recognized as a potential mediator of disease behavior. This is even more important with the development of a number of immune-based therapies. Based on these considerations, we evaluated peripheral blood absolute lymphocyte count (ALC) as an easily accessible marker representing immune microenvironment at diagnosis and after treatment of MM. We retrospectively evaluated 11 427 patients diagnosed with MM between 2000 and 2019 at Veterans Administration hospitals using ALC obtained closest to diagnosis and up to 2.5 years thereafter. Patients were stratified into 3 ALC categories: severely low, low, and normal (<1 × 103/μL, 1 × 103/μL to 1.5 × 103/μL, and >1.5 × 103/μL, respectively). Lymphopenia (including severely low and low ALC) was present in 53% of patients at MM diagnosis and was associated with inferior overall survival (OS). The median OS for patients with severely low, low, and normal ALC at diagnosis was 2.7, 3.3, and 4.2 years (P < .001), respectively. Moreover, persistent or new development of lymphopenia during treatment and follow-up was also associated with inferior OS. Our findings support the use of ALC as a biomarker for risk stratification in MM.
Cancer cachexia and weight loss before CAR T-cell therapy for lymphoma are independently associated with poor outcomes
Authors: Valtis Yannis K. , Devlin Sean , Shouval Roni , Rejeski Kai , Corona Magdalena , Luna De Abia Alejandro , Rivas-Delgado Alfredo , Luttwak Efrat , Cassanello Giulio , Landego Ivan , Schöder Heiko , Bedmutha Akshay , Boardman Alexander , Shah Gunjan L. , Scordo Michael , Perales Miguel-Angel , Salles Gilles , Palomba M. Lia , Shah Urvi A. , Park Jae H.
Published: October 2024

Chimeric antigen receptor (CAR) T-cell therapy has transformed the care of lymphoma, yet many patients relapse. Several prognostic markers have been associated with CAR T-cell outcomes, such as tumor burden, response to bridging chemotherapy, and laboratory parameters at the time of lymphodepletion or infusion. The effect of cancer cachexia and weight loss before CAR T cells on toxicity and outcomes is not well understood. Here, we present a retrospective single-institution cohort study of 259 patients with lymphoma treated with CAR T cells between 2017 and 2023. We observed that patients with >5% decrease in their body mass index in the 3 months preceding CAR T-cell treatment (weight loss group; all meeting one of the commonly accepted definitions of cancer cachexia) had higher disease burden and inflammatory parameters (C-reactive protein, ferritin, interleukin-6, and tumor necrosis factor α) at the time of lymphodepletion and CAR T-cell infusion. Patients with weight loss experienced higher rates of grade 3+ neurotoxicity and early hematotoxicity, but those effects were not seen upon multivariable adjustment. However, in both univariate and multivariable analysis, patients with weight loss had worse response rates, overall survival, and event-free survival, indicating that weight loss is an independent poor prognostic factor. Our data suggest that weight loss in the 3 months preceding CAR T-cell therapy represents a worrisome “alarm signal” and a potentially modifiable factor, alongside tumor burden and inflammation, and warrants further investigation in patients treated with CAR T-cell therapy.
Factors impacting post-nephrostomy-tube removal urine leak after percutaneous nephrolithotomy: does the calyx of access make a difference?
Authors: Maheshwari Pankaj N. , Goyal Aditya S. , Shrivastava Pushkar , Kolsawala Hussain , Agrawal Pratik J. , Bhatt Nakul J. , Harne Swapnil G.
Published: October 2024

Background

The aim of this study was to identify the factors that impact the post- percutaneous nephrolithotomy (PCNL) urine leak (UL) following nephrostomy tube removal and to assess if the calyx of entry made any difference.

Materials and methods

In this retrospective study, from April 2016 to May 2019, all the patients undergoing conventional percutaneous nephrolithotomy by a single 24 Fr access with complete stone clearance were evaluated. Patients with urine leak for > 4 h after nephrostomy tube removal were included in the urine leak group (n = 18), while the non-urine leak group (n = 60) comprised patients with urine leak for < 4 h. These groups were compared for demographic, renal, stone-related and peri-operative factors with special stress on calyx of access.

Results

The urine leak group had significantly older (mean 48 vs. 31 years, p = 0.003) patients with a higher proportion of diabetes mellitus (33% vs. 11%, p = 0.03). They also had a significantly greater (grade ≥ 3) hydronephrosis (55.5% vs. 10%, p < 0.001) and significantly reduced cortical thickness (mean 6.4 vs. 10.3 mm, p = 0.001). They had a nephrostomy tube in situ post-operatively for a longer duration (mean 52.3 vs. 34.5 h, p = 0.002). Interestingly 100% leaks happened from the middle/lower calyx tract and none from the upper calyceal access (p < 0.001). On multivariable regression analysis, grade ≥ 3 hydronephrosis with thin cortex, middle/lower calyceal access and keeping the nephrostomy tube for prolonged duration post-operatively were independent predictors of urine leak. There was no risk of leak from upper calyx access.

Conclusion

There is negligible risk of urine leak from upper calyx access so the possibility of hydrothorax after nephrostomy tube removal is minimal.
Synergistic potential of Leu10-teixobactin and cefepime against multidrug-resistant Staphylococcus aureus
Authors: Koh Augustine Jing Jie , Hussein Maytham , Thombare Varsha , Crawford Simon , Li Jian , Velkov Tony
Published: October 2024

Staphylococcus aureus (S. aureus) is a significant Gram-positive opportunistic pathogen behind many debilitating infections. β-lactam antibiotics are conventionally prescribed for treating S. aureus infections. However, the adaptability of S. aureus in evolving resistance to multiple β-lactams contributed to the persistence and spread of infections, exemplified in the emergence of methicillin-resistant S. aureus (MRSA). In the present study, we investigated the efficacies of the synthetic teixobactin analogue, Leu10-teixobactin, combined with the penicillinase-resistant cephalosporin cefepime against MRSA strains. The Leu10-teixobactin and cefepime combination exerted synergism against most strains tested in broth microdilution assay. Time-kill profiles showed that both Leu10-teixobactin and cefepime predominantly exhibited synergistic activity, with > 2.0-log10CFU decrease compared to monotherapy at 24 h. Moreover, biofilm assays revealed a significant inhibition of biofilm production in ATCC™43300 cells treated with sub-MICs of Leu10-teixobactin and cefepime. Subsequent electron microscopy studies showed more extensive damage with the combination therapy compared to monotherapies, including aberrant bacterial morphology, vesicle formation and substantial lysis, indicating combined damage to the cell wall. Quantitative real-time PCR revealed marked perturbation of genes mecA, sarA, atlA, and icaA, substantiating the apparent mode of combined antibacterial action of both antibiotics against peptidoglycan synthesis and initial biofilm production. Hence, the study highlights the prospective utility of the Leu10-teixobactin-cefepime combination in treating MRSA infections via β-lactam potentiation.
“The stay here is, of course, not appropriate for an old person”: the perspective of healthcare providers on older patients in the emergency department
Authors: Deutschbein Johannes , Wagenknecht Andreas , Gilles Gabriela , Möckel Martin , Schenk Liane
Published: October 2024

Background

In aging societies, emergency departments (ED) face an increasing number of older, geriatric patients. Research shows that older emergency patients have a greater burden of comorbidities and a higher risk of adverse events. It has been questioned whether contemporary ED structures can meet the specific needs and characteristics of older patients. Little is known about how professional health care providers perceive and experience ED care for older patients. This study aimed to get insight into the perspective of healthcare providers working with older ED patients and to explore the challenges they experience in their daily work.

Methods

The study used a qualitative research design with a social-constructivist perspective and a Grounded Theory based methodology. Data were collected through qualitative interviews with N = 25 healthcare providers from different urban EDs in Berlin, Germany, and adjacent healthcare institutions. Following the Ground Theory approach, categories and central themes were identified, analyzed, and interpreted to gain a comprehensive understanding of the healthcare provider perspective.

Results

The interviews revealed a significant and increasing relevance of geriatric ED patients for healthcare providers. However, there was no shared definition of ‘the geriatric patient’. Most interviewees found ED structures to be inadequate for older patients. They described specific challenges, such as information gathering and safety risks in the ED, as well as an increased use of resources (both time and personnel) when caring for older patients. In addition, specific problems in the collaboration with other professions and institutions were addressed, namely nursing homes, hospital wards, consultations, and the hospital social service.

Conclusion

Healthcare providers experience a structural mismatch between contemporary EDs and the specific needs of geriatric patients. They are aware of the vulnerabilities of geriatric patients and try to compensate for inherent structural shortcomings. Such structures and limited resources often cause practical, organizational, and ethical problems. There is a great need to develop, implement, and evaluate systematic approaches and care concepts that address the specifics of ED care for geriatric patients.
Medications for community pharmacists to dose adjust or avoid to enhance prescribing safety in individuals with advanced chronic kidney disease: a scoping review and modified Delphi
Authors: Wilson Jo-Anne , Ratajczak Natalie , Halliday Katie , Battistella Marisa , Naylor Heather , Sheffield Maneka , Marin Judith G. , Pitman Jennifer , Kennie-Kaulbach Natalie , Trenaman Shanna , Gillis Louise
Published: October 2024

Background

Community pharmacists commonly see individuals with chronic kidney disease (CKD) and are in an ideal position to mitigate harm from inappropriate prescribing. We sought to develop a relevant medication list for community pharmacists to dose adjust or avoid in individuals with an estimated glomerular filtration rate (eGFR) below 30 mL/min informed through a scoping review and modified Delphi panel of nephrology, geriatric and primary care pharmacists.

Methods

A scoping review was undertaken to identify higher risk medications common to community pharmacy practice, which require a dose adaptation in individuals with advanced CKD. A 3-round modified Delphi was conducted, informed by the medications identified in our scoping review, to establish consensus on which medications community pharmacists should adjust or avoid in individuals with stage 4 and 5 CKD (non-dialysis).

Results

Ninety-two articles and 88 medications were identified from our scoping review. Of which, 64 were deemed relevant to community pharmacy practice and presented for consideration to 27 panel experts. The panel consisted of Canadian pharmacists practicing in nephrology (66.7%), geriatrics (18.5%) and primary care (14.8%). All participants completed rounds 1 and 2 and 96% completed round 3. At the end of round 3, the top 40 medications to adjust or avoid were identified. All round 3 participants selected metformin, gabapentin, pregabalin, non-steroidal anti-inflammatory drugs, nitrofurantoin, ciprofloxacin and rivaroxaban as the top ranked medications.

Conclusion

Medications eliminated by the kidneys may accumulate and cause harm in individuals with advanced chronic kidney disease. This study provides an expert consensus of the top 40 medications that community pharmacists should collaboratively adjust or avoid to enhance medication safety and prescribing for individuals with an eGFR below 30 mL/min.
Sitting foot: posture dependent changes of volume, edema and perfusion of the foot. A prospective interventional study with 27 volunteers
Authors: Freund Wolfgang , Wikstroem Peter , Wunderlich Arthur P. , Schuetz Uwe , Beer Meinrad
Published: October 2024

Background

Sitting is known to be bad for your cardiovascular health. We furthermore hypothesized that sitting posture will reduce perfusion of the foot and increase edema, possibly predisposing to disease like osteochondritis.

Methods

We included 27 healthy volunteers and performed MRI measurements including arterial spin labelling (ASL) and intravoxel incoherent motion (IVIM) perfusion as well as short tau inversion recovery (STIR) edema measurement and 3D volumetry. After randomization, the elevation of one foot during the day was used as an intervention.

Results

Intra- and interrater variability was 1–6%. ASL perfusion measurement was hindered by artifacts. IVIM perfusion showed no significant changes during supine measurements. Volumetry could demonstrate a highly significant (p = 0.00005) volume increase, while the intervention led to a significant (p = 0.0076) volume decrease during the day. However, the water content in STIR remained unchanged and the normalized (quotient bone/muscle) edema was reduced on the control side (p = 0.006) and increased on the intervention side (p = 0.01).

Conclusions

Sitting all day leads to swelling of the healthy foot. Compensation in healthy subjects seems to prevent lasting perfusion changes or edema evolution in the bone despite an increase of muscle signal and volume increase. Thus, the etiology of osteochondritis needs further studies.