bluuebunny/crossref_metadata_2025 huggingface dataset:
Early left ventricular unloading after venoarterial extracorporeal membrane oxygenation: 1-year outcomes of the EARLY-UNLOAD randomized clinical trial
Authors: Lim Yongwhan , Kim Min Chul , Lee Seung Hun , Park Seongho , Ahn Joon Ho , Hyun Dae Young , Cho Kyung Hoon , Jung Yong Hun , Jeong In-Seok , Ahn Youngkeun
Published: January 2025

Aims

The long-term effects of early left ventricular (LV) unloading after venoarterial extracorporeal membrane oxygenation (VA-ECMO) remain unclear.

Methods and results

The EARLY-UNLOAD trial was a single-centre, investigator-initiated, open-label, randomized clinical trial involving 116 patients with cardiogenic shock (CS) undergoing VA-ECMO. The patients were randomly assigned to undergo either early routine LV unloading by transseptal left atrial cannulation within 12 h after randomization or the conventional approach, which permitted rescue transseptal cannulation in case of an increased LV afterload. The pre-specified secondary endpoints at 1 year included all-cause mortality, cardiac mortality, non-cardiac mortality, rehospitalization for heart failure (HF), and the composite of all-cause mortality or rehospitalization for HF. At 1 year, data for 114 of 116 patients (98.3%) were available for analysis. All-cause death had occurred in 33 of 58 patients (56.9%) in early group and 32 of 56 patients (57.1%) in conventional group {hazard ratio [HR], 0.97 [95% confidence interval (CI), 0.60 to 1.58], P = 0.887}. There was no significant difference in cardiac or non-cardiac mortality. Among 61 survivors at 30 days, the incidence of rehospitalization for HF at 1 year was comparable between two groups [HR, 1.17 (95% CI 0.43 to 3.24), P = 0.758]. The incidence of the composite outcome of all-cause mortality or rehospitalization for HF also did not differ between the groups [HR, 1.01 (95% CI 0.69 to 1.76), P = 0.692].

Conclusion

Among patients with CS undergoing VA-ECMO, early routine LV unloading did not improve clinical outcomes at 1 year of follow-up.

Registration

ClinicalTrials.gov: NCT04775472
Patients perspectives on integrating eHealth in regular care pathways for atrial fibrillation: evaluating photoplethysmography for remote self-assessment
Authors: van Mourik Manouk J W , Keijsers Lotte , van der Velden Rachel M J , Vorstermans Bianca , Crijns Harry J G M , Muris Jean W M , Linz Dominik K , Gidding-Slok Annerika
Published: January 2025

Aims

Smartphone applications for heart rate and rhythm assessment are increasingly used for the management of atrial fibrillation (AF). Although the use of a photoplethysmography (PPG)-based smartphone application with subsequent (tele)consultations for AF management has been proven feasible in the TeleCheck-AF project, specific needs, and expectations of patients with AF are unclear. The aim of this study is to evaluate patients’ perspectives on the use of remote PPG-based electronical health (eHealth) integrated in regular care pathways for AF.

Methods and results

A qualitative study was conducted among patients with known AF, who have used a PPG-based smartphone application around scheduled (tele)consultations. Semi-structured interviews were audio-recorded and transcribed verbatim. Data were analysed according to conventional content analysis.

In total, 14 patients were interviewed. Five main themes were defined after analysis, i.e. smartphone application usability, requirements for eHealth implementation, remote self-assessment, patient engagement, and blended care (i.e. combining digital and face-to-face care). Overall, the participants were positive about the use of the PPG-based smartphone application and subsequent (tele)consultation. Using this application made the participants feel involved and led to active participation. In addition, the healthcare provider-patient relationship appeared an important aspect for adequate implementation. Particularly, timely consultation was found important, to discuss the results with their healthcare provider.

Conclusion

The results of this study emphasize the importance of blended care for the implementation of remote PPG-based eHealth in AF management. The use of a PPG-based smartphone application in regular care can support patient engagement and subsequently the process of shared decision making.
Challenges and strategies for effective recruitment and retention of participants in clinical research studies
Authors: Klompstra Leonie , Strömberg Anna , Jaarsma Tiny , Hendriks Jeroen M
Published: January 2025

Effective recruitment and retention of participants in clinical research studies are critical to be able to draw meaningful and valid conclusions in research studies. However, there are multiple challenges related to communication, generalizability, and logistics. Researchers must address and overcome these challenges to ensure robust research outcomes. Effective strategies include honest and clear communication, awareness of reasons for (non)-participation, incentivization, and reimbursements of expenses as well as co-designing interventions and research protocols. This paper outlines common issues in participant recruitment and retention and provides practical strategies to overcome challenges.
Swarming bacteria exhibit developmental phase transitions to establish scattered colonies in new regions
Authors: Zdimal Amanda M , Di Dio Giacomo , Liu Wanxiang , Aftab Tanya , Collins Taryn , Colin Remy , Shrivastava Abhishek
Published: January 2025

The collective surface motility and swarming behavior of microbes play a crucial role in the formation of polymicrobial communities, shaping ecosystems as diverse as animal and human microbiota, plant rhizospheres, and various aquatic environments. In the human oral microbiota, T9SS-driven gliding bacteria transport non-motile microbes and bacteriophages as cargo, thereby influencing the spatial organization and structural complexity of these polymicrobial communities. However, the physical rules governing the dispersal of T9SS-driven bacterial swarms are barely understood. Here, we collected time-lapse images, under anaerobic conditions, of developing swarms of a T9SS-driven microbe common to the human oral microbiota. Tracking of swarms revealed that small peripheral flares emerging from a colony develop structures that resemble fireworks displaying a chrysanthemum effect and flower-like patterns that convert to wave-like patterns and which further evolve into scattered microcolonies. Particle-image velocimetry showed density-dependent phase transitions and initial vorticity within these emerging patterns. Numerical simulations demonstrate that these patterns arise due to changes in swarm speed and alignment strength. Our data reveal a strategy used by an anaerobic swarming bacterium to control swarm behavior, resulting in scattered microcolonies distant from the mother colony, thus reducing competition for resources among colony members. This might ensure species survival even if conditions change drastically in one location of the human oral cavity.
Electronic Health Record Design Impacts Clinician Ordering Behavior: An Interrupted Time Series Analysis
Authors: Wilber Eli P , Burd Eileen M , Fitts Eric C , Jacob Jesse T , Suchindran Sujit
Published: January 2025

Background

Diagnostic stewardship is the science of improving diagnostic test use. Whether electronic health record (EHR) design influences clinician diagnostic testing behavior and electronic medical record interventions can improve diagnostic stewardship outcomes are key questions. We leveraged the natural experiment of a recent change in EHR platforms to investigate if changing how 2 commonly misused tests, blood cultures for acid-fast bacilli (AFB) and fungi, are displayed affected their use.

Methods

We performed a retrospective chart review of all AFB and fungal blood cultures at 4 hospitals with a shared EHR. The preintervention and postintervention periods were 52 and 26 weeks, respectively. The culture rate was standardized per 1000 patient-days and segmented into 2-week periods. Pre- and postintervention median rates were compared with the Wilcoxon rank sum test and further analyzed with an interrupted time series (ITS) analysis using a quasi-Poisson regression model.

Results

The biweekly median AFB blood culture rate decreased by 41.6% in the postintervention period (0.46/1000 patient-days vs 0.79/1000 patient-days, P < 0.001). The median rate of fungal blood cultures decreased by 54.3% in the postintervention period (0.42/1000 patient-days vs 0.92/1000 patient-days, P < 0.001). In ITS analysis, the EHR change was associated with a level change in AFB (−31.8%, 95% CI: −54.6% to +2.6%) and fungal (−44.6%, 95% CI: −59.3% to −24.7%) blood culture use.

Conclusions

An electronic medical record design change resulted in decreased use of 2 commonly misused diagnostic tests. This highlights the impact of EHR design on clinician behavior and diagnostic stewardship programs’ potential to reduce waste.
The Role of the Clinical Laboratory in Diagnostic Stewardship and Population Health
Authors: Crawford James M , Shotorbani Khosrow , Swanson Kathleen
Published: January 2025

Background

As healthcare identifies new opportunities to provide patient services and moves from volume to value payment models, the clinical laboratory is in an ideal position to serve as a catalyst for these changes. In 2017, the Project Santa Fe Foundation (PSFF) was founded to support the clinical laboratory’s role to promote the objectives of population health and value-based healthcare. The initiative, known as Clinical Lab 2.0, uses longitudinal laboratory data to create actionable insights that can lead to improved patient and population outcomes, optimize the total cost of care, and reduce financial risk for stakeholders.

Content

The Clinical Lab 2.0 model was developed by a coalition of laboratory leaders to support clinical laboratories in the implementation of this new paradigm that moves beyond the provision of high-specificity and high-accuracy transactional test results and promotes “well care” and population health.

To provide leadership for Clinical Lab 2.0 across healthcare, promote dissemination of these concepts to clinical laboratories, and create evidence of laboratory’s value; the Foundation has several ongoing initiatives. The first initiative is the conduct of both single-site and multisite demonstration projects at PSFF member sites. The second ongoing initiative for the Foundation is the provision of guidance documents to support clinical laboratories in the implementation of Clinical Lab 2.0 and promote policy development. PSFF has developed 2 types of guidance document tools: Position Statements and Laboratory-Driven Care Models.

This review summarizes the history, background, and initiatives for Clinical Lab 2.0 supported by the Project Santa Fe Foundation.
Establishing Referral Laboratory Testing Governance and Addressing “Miscellaneous” Test Orders across an Academic Health System
Authors: Chambliss Allison B , Deignan Joshua L , Isip Charlemagne , Trinh Monique , Werre William , Ziman Alyssa
Published: January 2025

Background

Referral (send-out) laboratories support clinical needs but may cause issues for hospitals or health systems related to regulations and governance, specimen logistics, test result availability, and cost and reimbursement. The use of a “miscellaneous” referral test order can increase risks of specimen collection or processing errors, result delays, and repeat testing.

Methods

We established an approved referral laboratory test list and a digital form for providers to request new referral tests. We collated laboratory stewardship committee decisions over a 20-month period. Separately, we retrospectively reviewed referral tests ordered as miscellaneous across our health system over 1 year. Subject matter experts identified appropriate tests to build as discretely orderable in the electronic health record. Following targeted provider notification of the new tests, we assessed their uptake and impact on result turnaround times for the first 5 built tests over 6 months.

Results

Our laboratory stewardship committee approved 16 of 27 provider requests to build new referral tests over the first 20 months following implementation of the new request process. In addition, 37 of the 100 most frequently ordered miscellaneous tests were recommended to be built as discrete orders. Uptake of the first 5 built tests (relative to providers continuing to use miscellaneous orders) averaged 64% over the first 6 months. Result turnaround times improved by an average of 1.1 days when the discrete orders were used.

Conclusions

We successfully established oversight of referral laboratory testing across our health system, pivoted orders away from miscellaneous, and observed improvements in turnaround times.
Teaching the Laboratory’s Role in Diagnostic Stewardship: Engaging Pathology Residents in a Quality Initiative to Improve Autoverification Rates
Authors: Maggiore Jack A , Kanakis Constantine E , Gant Kanegusuku Anastasia , Kahn Stephen E
Published: January 2025

Background

Our institution involves our pathology residents in departmental quality initiatives and in identifying needs for operational improvements. The solutions achieved by these projects have effects beyond the laboratory, and ultimately help to improve diagnostic stewardship by supporting the clinician’s ability to obtain necessary biochemical information at the right time. A project highlighting a successful venture is described here in which our investment in new total laboratory automation was not meeting our goals for autoverification rates, resulting in less than expected improvements to turnaround times (TAT).

Methods

To improve efficiency of the new laboratory automation, our third-year pathology residents examined the limitations to the verification process and current delta checks. They performed a literature review for the most updated evidence-based practices, examined clinical metrics such as TAT. The residents assessed their findings combined with the laboratory’s quality goals, and contributed to updating middleware rule modifications. Several chemistry analyte software rules were revised while others were eliminated.

Results

After implementation of the modifications autoverification rates improved from 78% to 89% within 2 months of rule revisions. Average TAT for STAT basic metabolic profile improved from 51 to 46 minutes.

Conclusions

This study demonstrates the benefits of involving pathology residents in quality improvement initiatives. Residents are skilled resources capable of evaluating laboratory workflow processes in the context of clinical need. In this process, the residents experience the responsibilities of laboratory administration and learn the role of the laboratory in diagnostic stewardship.
Increasing the Diagnostic Utility of Heparin-Induced Thrombocytopenia (HIT) Testing: An Academic Medical Center’s Utilization Analysis and Intervention
Authors: Parsons Meredith G , Hobbs Ryan A , Schmidt Julie , Merrill Anna E
Published: January 2025

Background

Heparin-induced thrombocytopenia (HIT) is a potentially life-threatening adverse drug reaction with numerous diagnostic challenges. Diagnosis of HIT begins with 4T score clinical assessment, followed by laboratory testing for those not deemed low risk. Laboratory testing for HIT includes screening [enzyme-linked immunosorbent assay (ELISA)] and confirmatory [serotonin release assay (SRA)] assays, wherein SRA testing can be pursued following a positive ELISA result. These tests aid diagnosis of HIT, but also introduce interpretive challenges, additional costs, and delays in clinical intervention.

Methods

A retrospective review of 1011 HIT ELISA and 169 SRA tests performed over 5 years was conducted. ELISA percent inhibition and ELISA low-heparin optical density (OD) were evaluated for positive predictive value (PPV). Based on these findings, HIT ELISA reporting and management algorithm changes were implemented and metrics compared for 5 months pre- and post-intervention to assess intervention success.

Results

Equivocal and positive HIT ELISA interpretation showed poor PPV based on percent inhibition (0.20 and 0.32, respectively). However, rising low-heparin OD correlated with increasing PPV (PPV of 0.00 for OD values 0.40–1.00, 0.29 for values 1.00–1.99, and 0.91 for values >2.00). Data-driven intervention decreased ELISA positivity rates (13% to 5%), decreased rates of SRA confirmatory testing overall (13% to 9%), decreased SRA testing rates for patients with non-negative ELISAs (78% to 43%), and increased heparin resumption (20% to 57%). Hematology consults remained relatively stable (78% and 86%).

Conclusions

Low-heparin OD-based HIT ELISA interpretation yielded enhanced PPV compared with percent inhibition-based interpretation. Implementation of data-driven changes improved testing stewardship and clinical management for patients with non-negative ELISAs.
Blood Culture Contamination and Diagnostic Stewardship: From a Clinical Laboratory Quality Monitor to a National Patient Safety Measure
Authors: Bunn Jake D , Cornish Nancy E
Published: January 2025

Laboratory analysis of blood cultures is vital to the accurate and timely diagnosis of bloodstream infections. However, the reliability of the test depends on clinical compliance with standard operating procedures that limit the risk of inconclusive or incorrect results. False-negative blood culture results due to inadequate volumes of blood can result in misdiagnosis, delay therapy, and increase patients’ risk of developing or dying from bloodstream infections. Likewise, commonly occurring bacteria or fungi on human skin (i.e., commensal organisms) can contaminate the blood culture during collection and increase the risk of false positives, compromising care and leading to unnecessary antibiotic therapy and prolonged hospitalization.

In December 2022, a Centers for Medicare & Medicaid Services (CMS) consensus-based entity (CBE) endorsed the Centers for Disease Control and Prevention’s (CDC) proposal for a new patient safety measure to address these concerns. CDC developed this quality measure to promote the standardization of blood culture best practices and improve laboratory diagnosis of bloodstream infections nationally. This special report will emphasize the importance of standardizing blood culture collection and describe the need for a national patient safety measure, new quality tools, and next steps.
Diagnostic Laboratory Stewardship in a Growing Integrated Delivery Network
Authors: Wilhelms Kelly W , Braun Derek A , Mochon A Brian , Lainhart William D , Porter Sheelagh M , Beuthin Brandie M A , Blasko Diane M , Shapiro Meghan J , Proytcheva Maria A
Published: January 2025

Background

Many organizations institute laboratory diagnostic stewardship (DS) programs to improve the utilization of laboratory resources.

Methods

In this paper, we describe the road to implementing laboratory DS in a large, not-for-profit integrated delivery network located in the western United States.

Results

Program structure, projects, challenges, and future opportunities are discussed, providing tactics and opportunities that facilities can employ to maximize their initial foray into the DS landscape.

Conclusions

With effective planning and organization, laboratory DS can be implemented by any organization to realize resource optimization and financial benefits while maintaining high levels of patient care.
Financial Analytics for Laboratory Stewardship: Using Data and Informatics to Increase Financial Returns for Labs and Decrease Financial Harm to Patients
Authors: Ibrahim Khalda A , Astion Michael L
Published: January 2025

Background

As clinical laboratories struggle to maintain their financial footing and as patients face mounting out-of-pocket expenses for diagnostic testing, being able to perform financial analysis of laboratory stewardship efforts has become an increasingly important skill.

Content

Understanding the revenue cycle as it relates to diagnostic testing is fundamental to selecting, designing, implementing, and evaluating laboratory stewardship interventions for maximum financial return. Leveraging the data and processes driving the revenue cycle can inform informatics-based interventions (such as clinical decision support) and allow deliberate financial analyses of stewardship-focused projects. For labs striving not only to ensure their own financial health but also to help their patients avoid financial toxicity, the most effective strategies often depend on developing productive partnerships with key players along the revenue cycle.

Financial laboratory analytics is an emerging skill set that can power laboratory stewardship efforts and whose benefits accrue to patients, clinicians, laboratories, and health systems.
The substance-exposed birthing person-infant/child dyad and health information exchange in the United States
Authors: Bourgeois Fabienne C , Sinha Amrita , Tuli Gaurav , Harper Marvin B , Robbins Virginia K , Jeffrey Sydney , Brownstein John S , Jilani Shahla M
Published: January 2025

Objective

Timely access to data is needed to improve care for substance-exposed birthing persons and their infants, a significant public health problem in the United States. We examined the current state of birthing person and infant/child (dyad) data-sharing capabilities supported by health information exchange (HIE) standards and HIE network capabilities for data exchange to inform point-of-care needs assessment for the substance-exposed dyad.

Material and Methods

A cross-map analysis was performed using a set of dyadic data elements focused on pediatric development and longitudinal supportive care for substance-exposed dyads (70 birthing person and 110 infant/child elements). Cross-mapping was conducted to identify definitional alignment to standardized data fields within national healthcare data exchange standards, the United States Core Data for Interoperability (USCDI) version 4 (v4) and Fast Healthcare Interoperability Resources (FHIR) release 4 (R4), and applicable structured vocabulary standards or terminology associated with USCDI. Subsequent survey analysis examined representative HIE network sharing capabilities, focusing on USCDI and FHIR usage.

Results

91.11% of dyadic data elements cross-mapped to at least 1 USCDI v4 standardized data field (87.80% of those structured) and 88.89% to FHIR R4. 75% of the surveyed HIE networks reported supporting USCDI versions 1 or 2 and the capability to use FHIR, though demand is limited.

Discussion

HIE of clinical and supportive care data for substance-exposed dyads is supported by current national standards, though limitations exist.

Conclusion

These findings offer a dyadic-focused framework for electronic health record-centered data exchange to inform bedside care longitudinally across clinical touchpoints and population-level health.
Aristotle’s dilemma
Authors: Kapsner Andreas
Published: January 2025

The contra-classicality of connexive logics presents a challenge to classical logic that is interestingly different from other non-classical logics, and discussions of that difference have been a main feature of the literature around connexive logic. Seldom, if ever, however, is the following question addressed: is this challenge more severe or less severe than the one presented by sub-classical logics (i.e. almost all other non-classical projects)? This paper will aim to show that, in fact, the connexive project, suitably unpacked, contains a charge that is not only different, but qualitatively more weighty than other non-classical logics. In order to make that argument, I introduce a new principle I call Aristotle’s Dilemma that is, I argue, closely related to the connexive axioms, and that gives an answer to this question. It also suggests an answer to a second question, namely why connective logics are not better known in philosophical logical circles, or, to the extent that they are, why it has taken so long. In part, I suggest, this is down to the unusual formal guise in which the connexive cause is normally voiced. Aristotle’s Dilemma offers a remedy to this.
Comparison of Two Interferon-Gamma Release Assays for Pediatric Tuberculosis Infection
Authors: Gaensbauer James T , Reves Randall R , Katz Dolly , Ahmed Amina , Venkatappa Thara
Published: January 2025

Introduction

Identifying tuberculosis infection (TBI) using interferon-gamma release assays (IGRAs) is a primary component of clinical and public health efforts to prevent pediatric tuberculosis (TB). Pediatric data comparing the 2 IGRAs in the United States are very limited. We compared the performance of the 2 IGRAs among a large pediatric cohort tested for TBI and assessed whether discordance might be due to quantitative results close to test cutoff values.

Methods

Children aged 0-15 years with both T-SPOT.TB (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests were identified from a US multicenter study enrolling people at elevated risk of TBI or progression to TB disease. Results were compared using McNemar’s Chi-square tests with stratification by age category and testing reason. Percent agreement and kappa statistics were also calculated. We characterized quantitative test results among children with discordant QFT-GIT-positive/T-SPOT-negative results.

Results

Among 3793 children, a higher number had positive QFT-GIT than T-SPOT (10.1% vs 7.4%, P < .001). This difference was noted for all age categories except <2 years, and for children with close-contact and non-close contact test indications. Among discordant QFT-GIT-positive/T-SPOT-negative children, lowering the positive threshold for T-SPOT to include borderline spot counts (5-7) did not eliminate the discordance, nor were QFT-GIT antigen-minus-nil results concentrated in the range just above the standard cutoff of 0.35 IU/mL.

Conclusions

In a large pediatric cohort tested for TBI, QFT-GIT had a higher proportion of positive results than T-SPOT, and discordance was not related to quantitative results close to the established diagnostic cutoffs.
Sex-Specific Effects in Acute Nicotine Vapor Exposure on Binge Drinking and Activity in the Central Amygdala and Ventral Tegmental Area
Authors: Echeveste Sanchez Maria , Guerry Hayley , Grady Shyenne , Herman Melissa
Published: January 2025

Introduction

The increasing prevalence of electronic nicotine delivery systems and alcohol drinking has led to increases in nicotine and alcohol co-use. However, the impact of ENDs on brain activity and binge drinking behavior is not fully understood.

Aims and Methods

We subjected female and male C57BL/6J mice to a voluntary drinking and electronic nicotine vapor exposure paradigm. We first established baseline drinking using a drinking-in-the-dark paradigm. In the third week, mice were exposed to 3 hours sessions of electronic nicotine vapor prior to ethanol access, and ethanol and water drinking levels were measured. Following the last nicotine vapor and drinking session we measured blood alcohol levels (BAL) and collected tissue to measure brain activity by cFos expression.

Results

Nicotine vapor exposure decreased both alcohol and water intake in males, only reduced ethanol intake in females, and did not alter binge alcohol intake in either sex. Nicotine and alcohol increased activity in the central amygdala in females but had no effect in males. In the ventral tegmental area (VTA) nicotine increased activity in females but alcohol did not produce any additional increases. Nicotine and alcohol-exposed males had significantly lower BAL as compared to females, suggesting sex differences in drinking patterns where males appeared to “front-load” and females drank more throughout the end of the session.

Conclusions

These results highlight important sex differences in the impact of nicotine and alcohol co-exposure and underscore the importance of further investigating the neurobiological effects of alcohol and nicotine on brain activity and metabolism in males and females.

Implications

With increasing nicotine and alcohol use, it is imperative to understand the neurobiological and behavioral consequences of co-use with a focus on sex differences. Using passive nicotine vapor inhalation and a binge drinking paradigm, we investigated the effects of nicotine and alcohol co-use in mice. We found sex differences in alcohol intake and brain activity from this poly-substance use approach. Nicotine decreased alcohol and water intake in males, only reduced alcohol intake in females, and did not change binge alcohol drinking. Alcohol and nicotine produced sex-specific increases in the central amygdala and only nicotine increased VTA activity.
Can Equity Option Returns Be Explained by a Factor Model? IPCA Says Yes
Authors: Goyal Amit , Saretto Alessio
Published: January 2025

A number of delta-hedged equity option strategies exhibit very large average returns. We show that much of the profitability of these strategies can be explained by an IPCA factor model. The economic magnitude of the return-adjustment produced by IPCA is impressive: even before transaction costs, the average IPCA alpha of 46 long-short trading strategies constructed on previously discovered signals, is close to zero and contrasts with average realized returns of over 80 basis points per month. Our IPCA model can be used as a benchmark for assessing the performance of other option portfolios.
Gut barrier integrity disruption in atopic dermatitis: truth or myth—a case–control study
Authors: El Sayed Naglaa M , Riad Merna A , Taleb Raghda S Z , El Morsy Eman H
Published: January 2025

Background

Gut dysbiosis has been linked to the onset and progression of various diseases, including atopic dermatitis, by disrupting the intestinal barrier integrity. In turn, it allows the translocation of microbes and toxins into the systemic circulation, which triggers an immune response.

Objectives

To measure serum levels of the gut integrity markers claudin 3 and intestinal fatty acid-binding protein in patients with atopic dermatitis.

Methods

This prospective study was conducted on 43 patients with atopic dermatitis. Healthy volunteers (n = 35) served as controls. The serum level of claudin 3 and intestinal fatty acid-binding protein were measured using an enzyme-linked immunosorbent assay for all participants.

Results

There were no significant differences in serum levels of claudin 3 and intestinal fatty acid-binding protein between patients with atopic dermatitis and the control group (P = 0.61 and 0.81, respectively). In addition, there was no significant correlation between the two markers, and different clinical and laboratory parameters (onset of disease, eczema area severity index, other allergic manifestations and serum IgE).

Conclusion

Alterations in the intestinal barrier may be absent in the ethnically distinct group of patients with atopic dermatitis included in our study. Nevertheless, our findings might have been influenced by factors such as the duration of the disease, diet and characteristics of the study population. Further studies are needed to investigate additional biomarkers or mechanisms that may be involved in atopic dermatitis pathogenesis, especially those related to the gut–skin axis.
Single-cell RNA-seq reveals that granulosa cells are a target of phthalate toxicity in the ovary
Authors: Mattson Erik , Warner Genoa R
Published: January 2025

Phthalates are known endocrine-disrupting chemicals and ovarian toxicants that are used widely in consumer products. Phthalates have been shown to exert ovarian toxicity on multiple endpoints, altering transcription of genes responsible for normal ovarian function. However, the molecular mechanisms by which phthalates act on the ovary are not well understood. In this study, we hypothesized that phthalates specifically target granulosa cells within the ovarian follicle. To test our hypothesis, we cultured whole mouse antral follicles for 96 h in the presence of vehicle or 10 µg/ml of a phthalate metabolite mixture. At the end of the culture period, follicles were dissociated into single-cell suspensions and subjected to single-cell RNA-sequencing. We used markers from published studies to identify cell-type clusters, the largest of which were granulosa and theca/stroma cells. We further identified subpopulations of granulosa, theca, and stromal cells and analyzed differentially expressed genes between the phthalate treatment and control. Granulosa cells, specifically mural granulosa cells, had the most differentially expressed genes. Pathway analysis of differentially expressed genes from the overall granulosa cell cluster revealed disruption of cell cycle and mitosis, whereas pathway analysis of the mural granulosa cell subcluster identified terms related to translation, ribosome, and endoplasmic reticulum. Our findings suggest that phthalates have both broad impacts on cell types and specific impacts on cellular subtypes, emphasizing the complexity of phthalate toxicity and highlighting how bulk sequencing can mask effects on vulnerable cell types.
Haemotoxicity of snakes: a review of pathogenesis, clinical manifestations, novel diagnostics and challenges in management
Authors: Alvitigala Bhawani Yasassri , Dissanayake Harsha A , Weeratunga Praveen N , Padmaperuma P A Chanya D , Gooneratne Lallindra Viranjan , Gnanathasan Christeine Ariaranee
Published: January 2025

Haemotoxicity is the most common complication of systemic envenoming following snakebite, leading to diverse clinical syndromes ranging from haemorrhagic to prothrombotic manifestations. Key haematological abnormalities include platelet dysfunction, venom-induced consumption coagulopathy, anticoagulant coagulopathy and organ-threatening thrombotic microangiopathy. Diagnostic methods include the bedside whole blood clotting test, laboratory coagulation screening and other advanced methods such as thromboelastogram and clot strength analysis. The primary management strategies are venom neutralisation with antivenom and correction of coagulopathy with blood component transfusions, while options such as plasma exchange are utilised in certain cases. Recent advancements in understanding the pathogenesis of haemotoxicity have facilitated the development of new diagnostic and treatment modalities. This review summarises current knowledge on the pathogenesis, diagnosis, clinical and laboratory manifestations and treatment of the haematological effects of snake envenoming. Furthermore, it highlights important challenges concerning diagnosis and management. Addressing these challenges is crucial for achieving the WHO's goal of reducing deaths and disabilities caused by snakebites by 2030.
Health economics of snakebite envenomation: A sub-Saharan African perspective
Authors: Ayesiga Innocent , Gmanyami Jonathan Mawutor , Akaka Alex , Kubwimana Olivier , Ternor Joshua Naatey , Hashim Ukasha Musa , Gyabaah Gertrude Ahenewaa , Turzin Justice Kwadwo , Kahwa Ivan
Published: January 2025

Sub-Saharan Africa (SSA) is affected by the high direct and indirect costs of snakebite envenomation. With >30% of global mortality, different economic barriers still exist, and effective strategies must be employed to avert the burden and promote quality of life. With the WHO target of reducing the number of snakebites by one-half by 2030, different aspects concerning snakebite envenomation economics must be evaluated, and potential strategies must be developed. Strategies such as exploring the different snakebite prevention interventions, and the costs associated with these interventions, must be prioritized through extensive research and targeted surveys. Information obtained from these surveys can be used to draft effective policies to minimize snakebite envenomation incidence, reduce the economic burden associated with envenomation and improve the quality of life of people at risk. In this narrative review, we evaluate the different aspects concerning the health economics of snakebite envenomation and explore the financial capacity of SSA countries to mitigate envenomation. Additionally, we propose multiple steps that could be undertaken to mitigate the financial burden of envenomation in SSA. Furthermore, we propose critical research strategies to minimize direct and indirect costs arising from snakebite envenomation in the region.
Medically important snakes in Sudan: an overview of distribution, clinical features and present challenges
Authors: Baleela Rania M H , Elamin Muhammad E M O , Mohammad Abubakr , Saeed Sara A K
Published: January 2025

Snakebite envenomation (SBE) is a neglected tropical disease. It causes substantial morbidity and mortality in Sudan. Despite its endemicity, there is a substantial lack of up-to-date data on venomous snakes and their geographical distribution in Sudan, with most information dating back to the early twentieth century. To address this gap, we conducted a narrative review of the literature on snakes and SBE in Sudan. This review involved systematic searches of databases, historical publications and online resources from 1908 to 2024. Integrating literature findings with personal field experiences to provide a comprehensive overview of the SBE situation in Sudan, we identified 19 medically significant snake species in Sudan from four families. These species exhibit a range of venom types and clinical effects, including neurotoxic, hemotoxic and cytotoxic envenomation. The most dangerous and important species are the carpet viper (Echis pyramidum), the Nubian cobra (Naja nubiae) and the Sudan burrowing asp (Atractaspis phillipsi). Challenges in snakebite management include the non-availability of specific antivenoms, inadequate healthcare infrastructure and reliance on traditional medicine. We recommend establishing a national snakebite registry, improving healthcare infrastructure, developing training programs for healthcare professionals and increasing public awareness. Strengthening international collaborations for antivenom production and investing in molecular research are also crucial for reducing the severity and associated morbidity of SBE in Sudan.
Health-seeking behaviours and traditional healer practices for snakebite in rural and tribal communities in southern India
Authors: Ralph Ravikar , Ramesh Rohan Michael , Jambugulam Mohan , Deborah Arpitha Anbu , Aruldas Kumudha , Moorthy Neal A , John Sushil Mathew , Walson Judd L , Zachariah Anand , Ajjampur Sitara Swarna Rao
Published: January 2025

Background

Nearly 60 000 Indians die of snakebite envenoming each year. Most deaths occur in rural communities and remote tribal settlements. We describe snakebite-related epidemiology and health-seeking behaviours in a rural (Timiri) and remote tribal block (Jawadhu Hills) in Tamil Nadu, India.

Methods

This cross-sectional survey used structured questionnaires for information pertaining to snakebites and their treatment in the preceding year. Treatment-seeking behaviour from the moment reported until recovery was mapped. Traditional healers residing in the two blocks were also surveyed.

Results

Snakebite incidence and mortality were 174/100 000 population and 2.7/100 000 population in Jawadhu Hills and 194/100 000 population and 2.6/100 000 population in Timiri, respectively. More snakebite victims applied tourniquets in Jawadhu Hills (90%) than in Timiri (69%). Traditional healers were the first contact for 64% in Jawadhu Hills. Ambulances and buses were reported as unavailable in Jawadhu Hills. Traditional healers in Jawadhu Hills did not refer snakebite victims to hospitals.

Conclusions

Three challenges to snakebite mitigation in Indian rural and tribal communities highlighted in this study are potentially harmful first aid, a disconnect between traditional healers and the public health system and a lack of emergency transport to health facilities. Addressing these challenges would necessitate community awareness, traditional healer engagement and improved means of public transportation.
Snakebite envenomation through a gender intersectionality lens in low- and middle-income countries
Authors: Ayesiga Innocent , Naggayi Shamim , Gmanyami Jonathan Mawutor , Akaka Alex , Kubwimana Olivier , Gyabaah Gertrude Ahenewaa , Katusiime Elizabeth , Hashim Ukasha Musa , Kahwa Ivan
Published: January 2025

Snakebite envenomation continues to affect lives globally, with >1.2 million envenomations and approximately 120 000 annual mortalities. Unfortunately, low- and middle-income countries (LMICs) contribute to >80% of these global statistics. With different targets set to minimize the impact of snakebite envenoming, such as halving the envenoming cases by 2030 from the World Health Organization (WHO), multiple initiatives are inevitable. Gender intersectionality and tropical disease research for infectious diseases of poverty, developed by the WHO, has championed the exploration of neglected diseases, stratifying them using gendered domains. However, minimal research using the gender intersectionality framework has been conducted to explore snakebite envenoming, especially among LMICs. Exploring snakebite envenomation through a gendered lens is critical in developing gender-specific interventions for the prevention and treatment of envenomation. This narrative review explores the available literature about snakebite envenomation in LMICs through a gender intersectionality lens. It provides insights into the existing gaps, especially regarding research using intersectionality frameworks and the gendered matrix. It further proposes avenues of research using these domains to understand snakebite envenomation, especially through the intersectionality lens.
Knowledge, perceptions and healthcare practices of communities for management of snakebites in Kamuli District, Eastern Uganda
Authors: Tusabe Joan , Muhoozi Michael , Kajungu Dan , Mukose Aggrey , Kasasa Simon , Sebina Kibira Simon Peter
Published: January 2025

Background

Snakebite is one of the neglected tropical diseases in Uganda affecting rural areas, especially during the rainy season. Households mainly rely on traditional remedies for management, which are not always effective, leading to disability and sometimes death. We explored the knowledge, perceptions and healthcare practices related to snakebites in Kamuli District.

Methods

We used the participatory research appraisal (PRA) method to conduct the study. Six PRA sessions were carried out in five purposively selected villages of Wankole subcounty, Kamuli District, as they reported a high number of snakebites. In addition, we conducted 15 in-depth interviews with current and past snakebite victims and 10 key informant interviews with professional healthcare providers and traditional healers. Audio files were transcribed and translated verbatim and data were analysed to identify themes. Analysis was conducted using ATLAS.ti version 8.0.

Results

Overall, the community considered snakebites a big problem that worsens during rainy seasons. Knowledge of snakebite management was inadequate. Perceptions about snakes and snakebites included snakes are related to traditions, ancestral spirits and witchcraft. Practices following snakebites included applying a tourniquet and the use of herbs, paraffin and a 500-shilling coin. Snakebites were associated with out-of-pocket expenditures and limited capacity to manage.

Conclusions

The study calls for policy changes to improve snakebite management in Eastern Uganda, highlighting gaps in knowledge and harmful practices. It emphasizes the need for health education and financial support for affected households. Collaboration between healthcare providers, traditional healers and the community is crucial for effective prevention and management.
Characteristics of snakebite patients due to Naja samarensis in the Philippines: a prospective hospital-based study
Authors: Aoki Yoshihiro , Paghubasan Jonathan , Tiglao Patrick Joseph , Sarmiento Marvin Jay , Arrieta Rustan , Tan Mariedel A , Sarsalijo Mardie S , Aquino Grace Joy B , Beronilla-Uraga Mercy Grace , Comandante John David L , Santamaria Emelia B , Malijan Greco Mark B , Suzuki Shuichi , Takahashi Kensuke , Yamano Shuhei , Smith Chris , Hayakawa Koichi , Tasaki Osamu , Agosto Lourdes C , Warrell David A , Ariyoshi Koya
Published: January 2025

Background

Little is known about snakebites by Naja samarensis, a species unique to the Philippines. The aim here is to describe the clinical and epidemiological characteristics of patients bitten by this medically important cobra in the Eastern Visayas.

Methods

A hospital-based prospective study analysed the features of snakebite patients attending Eastern Visayas Medical Center between June 2022 and May 2023. Logistic regression analysis identified the factors associated with severity.

Results

A total of 175 snakebite patients with five fatalities were included. Naja samarensis was most commonly implicated (n=49, 28.0%), although it could be definitively identified, by examining photographs of the snake responsible, in only four cases. The N. samarensis bites occurred in grass or rice fields, in daytime, and during farming activities, but the people bitten were most frequently students (34.7%) who were bitten at home (36.7%). Patients bitten by N. samarensis often presented with cytotoxic (63.3%) and neurotoxic signs (46.9%). Traditional remedies were common, resulting in delayed presentation to the hospital. Bites by N. samarensis, and older age (>44 y) were independently associated with severity (adjusted OR of 10.33 and 7.89, respectively).

Conclusion

Naja samarensis is a major cause of severe snakebites in this region. Pre-hospital treatment frequently involves wasted time and unproven traditional methods. Enhancement of public awareness is urgently needed. Development of a diagnostic test for species identification is warranted to improve future surveys and management.
Antivenom ineffectiveness in Echis carinatus sochureki envenoming: a five-year, single-centre experience from India
Authors: Gopalakrishnan Maya , Kumar PH Akhilesh , Tanwar Divya , Bhat KS Samarth , Choudhary Bharat , Garg Mahendra K
Published: January 2025

Background

Snakebite is a neglected tropical disease that causes significant morbidity and mortality in India. In this study, we describe the clinical characteristics and outcomes of Echis carinatus sochureki envenoming from Western Rajasthan. We document the clinical ineffectiveness of the currently available Indian polyvalent antivenom in managing E. c. sochureki envenoming.

Methods

In this ambispective study, conducted from 14 April 2019 to 15 April 2024, we enrolled all patients presenting to our emergency department at a tertiary care centre in Jodhpur, Rajasthan, with a history of snakebite. After they provided informed consent, the demographic details, bite geo-location, bite-to-antivenom time, antivenom dose, coagulation profile, mortality and duration of hospital stay of those patients with E. c. sochureki envenoming were recorded.

Results

Of 210 patients screened, 105 had E. c. sochureki envenoming, 103 venom-induced consumption coagulopathy, 36 (34.3%) local bleeding and 55 (52.3%) systemic bleeding. The median bite-to-antivenom time was 2 (IQR: 1.13–4.0) h. The median antivenom dose was 22 (IQR: 10–30) vials. Of 92 patients who received antivenom, 63 (68.4%) were unresponsive. Total antivenom dose and geographical location (West zone) were significant predictors of antivenom unresponsiveness. Fifty-three of 70 patients (75.7%) had delayed hypofibrinogenaemia. The mean hospital stay was 8.3±7.1 d with nine (8.6%) mortalities.

Conclusions

Our study highlights the alarming finding of poor antivenom response to E. c. sochureki envenoming, with significant clinical bleeding and delayed coagulopathy. There is an urgent need for region-specific antivenom in Western India.