PLoS One. 2025 Feb 3;20(2):e0318070. doi: 10.1371/journal.pone.0318070. eCollection 2025.

ABSTRACT

Electrocardiogram (ECG) signals are crucial in diagnosing cardiovascular diseases (CVDs). While wavelet-based feature extraction has demonstrated effectiveness in deep learning (DL)-based ECG diagnosis, selecting the optimal wavelet base poses a significant challenge, as it directly influences feature quality and diagnostic accuracy. Traditional methods typically rely on fixed wavelet bases chosen heuristically or through trial-and-error, which can fail to cover the distinct characteristics of individual ECG signals, leading to suboptimal performance. To address this limitation, we propose a reinforcement learning-based wavelet base selection (RLWBS) framework that dynamically customizes the wavelet base for each ECG signal. In this framework, a reinforcement learning (RL) agent iteratively optimizes its wavelet base selection (WBS) strategy based on successive feedback of classification performance, aiming to achieve progressively optimized feature extraction. Experiments conducted on the clinically collected PTB-XL dataset for ECG abnormality classification show that the proposed RLWBS framework could obtain more detailed time-frequency representation of ECG signals, yielding enhanced diagnostic performance compared to traditional WBS approaches.

PMID:39899639 | DOI:10.1371/journal.pone.0318070

PLoS Comput Biol. 2025 Feb 3;21(2):e1012753. doi: 10.1371/journal.pcbi.1012753. Online ahead of print.

ABSTRACT

Animal behavior spans many timescales, from short, seconds-scale actions to daily rhythms over many hours to life-long changes during aging. To access longer timescales of behavior, we continuously recorded individual Drosophila melanogaster at 100 frames per second for up to 7 days at a time in featureless arenas on sucrose-agarose media. We use the deep learning framework SLEAP to produce a full-body postural dataset for 47 individuals resulting in nearly 2 billion pose instances. We identify stereotyped behaviors such as grooming, proboscis extension, and locomotion and use the resulting ethograms to explore how the flies' behavior varies across time of day and days in the experiment. We find distinct daily patterns in all stereotyped behaviors, adding specific information about trends in different grooming modalities, proboscis extension duration, and locomotion speed to what is known about the D. melanogaster circadian cycle. Using our holistic measurements of behavior, we find that the hour after dawn is a unique time point in the flies' daily pattern of behavior, and that the behavioral composition of this hour tracks well with other indicators of health such as locomotion speed and the fraction of time spend moving vs. resting. The method, data, and analysis presented here give us a new and clearer picture of D. melanogaster behavior across timescales, revealing novel features that hint at unexplored underlying biological mechanisms.

PMID:39899595 | DOI:10.1371/journal.pcbi.1012753

PLoS One. 2025 Feb 3;20(2):e0317359. doi: 10.1371/journal.pone.0317359. eCollection 2025.

ABSTRACT

Japanese table grapes are quite expensive because their production is highly labor-intensive. In particular, grape berry pruning is a labor-intensive task performed to produce grapes with desirable characteristics. Because it is considered difficult to master, it is desirable to assist new entrants by using information technology to show the recommended berries to cut. In this research, we aim to build a system that identifies which grape berries should be removed during the pruning process. To realize this, the 3D positions of individual grape berries need to be estimated. Our environmental restriction is that bunches hang from trellises at a height of about 1.6 meters in the grape orchards outside. It is hard to use depth sensors in such circumstances, and using an omnidirectional camera with a wide field of view is desired for the convenience of shooting videos. Obtaining 3D information of grape berries from videos is challenging because they have textureless surfaces, highly symmetric shapes, and crowded arrangements. For these reasons, it is hard to use conventional 3D reconstruction methods, which rely on matching local unique features. To satisfy the practical constraints of this task, we extend a deep learning-based unsupervised monocular depth estimation method to an omnidirectional camera and propose using it. Our experiments demonstrate the effectiveness of the proposed method for estimating the 3D positions of grape berries in the wild.

PMID:39899513 | DOI:10.1371/journal.pone.0317359

Circulation. 2025 Feb 4;151(5):e35-e36. doi: 10.1161/CIRCULATIONAHA.124.072688. Epub 2025 Feb 3.

NO ABSTRACT

PMID:39899631 | DOI:10.1161/CIRCULATIONAHA.124.072688

PLoS Genet. 2025 Feb 3;21(2):e1011582. doi: 10.1371/journal.pgen.1011582. Online ahead of print.

ABSTRACT

A first ethanol exposure creates three memory-like states in Drosophila. Ethanol memory-like states appear genetically and behaviorally paralleled to the canonical learning and memory traces anesthesia-sensitive, anesthesia-resistant, and long-term memory ASM, ARM, and LTM. It is unknown if these ethanol memory-like states are also encoded by the canonical learning and memory circuitry that is centered on the mushroom bodies. We show that the three ethanol memory-like states, anesthesia-sensitive tolerance (AST) and anesthesia resistant tolerance (ART) created by ethanol sedation to a moderately high ethanol exposure, and chronic tolerance created by a longer low concentration ethanol exposure, each engage the mushroom body circuitry differently. Moreover, critical encoding steps for ethanol memory-like states reside outside the mushroom body circuitry, and within the mushroom body circuitry they are markedly distinct from classical memory traces. Thus, the first ethanol exposure creates distinct memory-like states in ethanol-specific circuits and impacts the function of learning and memory circuitry in ways that might influence the formation and retention of other memories.

PMID:39899623 | DOI:10.1371/journal.pgen.1011582

Diabetes Care. 2025 Feb 3:dc242039. doi: 10.2337/dc24-2039. Online ahead of print.

ABSTRACT

OBJECTIVE: Glucocorticoids (GCs) are potent anti-inflammatory drugs, but strategies to prevent side effects are lacking. We investigated whether metformin could prevent GC-related toxicity and explored the underlying mechanisms.

RESEARCH DESIGN AND METHODS: This single-center, randomized, placebo-controlled, double-blind, crossover trial compared metformin with placebo during high-dose GC treatment in 18 lean, healthy, male study participants. The trial was conducted at the University Hospital Basel, Switzerland. Participants received prednisone 30 mg/d in combination with metformin or placebo for two 7-day periods (1:1 randomization). The primary outcome, change in insulin sensitivity, was assessed using a two-sided paired t test. Before and after each study period, we conducted a mixed-meal tolerance test, blood metabolomics, and RNA sequencing of subcutaneous adipose tissue biopsy specimens.

RESULTS: Metformin improved insulin sensitivity as assessed by the Matsuda index (n = 17; mean change: -2.73 ± 3.55 SD for placebo, 2.21 ± 3.95 for metformin; mean difference of change -4.94 [95% CI, -7.24, -2.65)]; P < 0.001). Metabolomic and transcriptomic analyses revealed that metformin altered fatty acid flux in the blood and downregulated genes involved in fatty acid synthesis in adipose tissue. Metformin reduced markers of protein breakdown and bone resorption. Furthermore, metformin downregulated genes responsible for AMPK inhibition and affected GLP1 and bile acid metabolism.

CONCLUSIONS: Metformin prevents GC-induced insulin resistance and reduces markers of dyslipidemia, myopathy, and, possibly, bone resorption through AMPK-dependent and -independent pathways.

PMID:39899467 | DOI:10.2337/dc24-2039

Diabetes. 2025 Feb 3:db240360. doi: 10.2337/db24-0360. Online ahead of print.

ABSTRACT

Glucolipotoxicity, caused by combined hyperglycemia and hyperlipidemia, results in β-cell failure and type 2 diabetes via cellular stress-related mechanisms. Activating transcription factor 4 (Atf4) is an essential effector of stress response. We show here that Atf4 expression in β-cells is minimally required for glucose homeostasis in juvenile and adolescent mice but it is needed for β-cell function during aging and under obesity-related metabolic stress. Henceforth, Atf4-deficient β-cells older than 2 months after birth display compromised secretory function under acute hyperglycemia. In contrast, they are resistant to acute free fatty acid-induced dysfunction and reduced production of several factors essential for β-cell identity. Atf4-deficient β-cells down-regulate genes involved in protein translation. They also upregulate several lipid metabolism or signaling genes, likely contributing to their resistance to free fatty acid-induced dysfunction. These results suggest that Atf4 activation is required for β-cell identity and function under high glucose. But Atf4 activation paradoxically induces β-cell failure in high levels of free fatty acids. Different transcriptional targets of Atf4 could be manipulated to protect β-cells from metabolic stress-induced failure.

PMID:39899446 | DOI:10.2337/db24-0360

PLoS One. 2025 Feb 3;20(2):e0317907. doi: 10.1371/journal.pone.0317907. eCollection 2025.

ABSTRACT

OBJECTIVES: To estimate the prevalence of polypharmacy among community-dwelling adults in the UK and determine its association with mortality, hospitalization, adverse drug reactions and falls at one and five years. To also determine the effect of polypharmacy on the outcomes in different patient groups.

METHODS: A retrospective cohort study was carried out using 1000 patients aged 75 years and above from the Clinical Practice Research Datalink. The study periods for the one- and five-years analysis were January 2010-December 2010 and January 2010-December 2014 respectively. Sociodemographic and clinical variables were retrieved using medical and product codes. Polypharmacy was defined as the use of five or more medicines. The association between polypharmacy and mortality, falls, adverse drug reactions, or hospitalization was determined using cox regression analysis while confounding for age, sex, Charlson's comorbidity index, potentially inappropriate medicines, hospitalization prior to study, and falls prior to study. Subgroup analysis was used to determine the effect of polypharmacy on the outcomes for different patient groups.

KEY FINDINGS: 977 people were reviewed. 36% were male and the mean age was 83 years. The prevalence of polypharmacy was 47%. Adjusted hazard ratios with their 95% confidence intervals for association between polypharmacy and outcomes at five years were: mortality 1.60 (1.30-2.00), hospitalization 1.49 (1.30-1.70), falls 1.49 (0.90-2.40) and adverse drug reactions 0.97 (0.50-1.80). The results for the one-year analysis were mortality 2.37 (1.40-3.90), hospitalization 2.47 (1.40-4.30), and falls 0.37 (0.03-4.00).

CONCLUSION: Polypharmacy was found to be a risk factor for mortality and hospitalization. The risk increased with an increase in age, potentially inappropriate medicines and comorbidities.

PMID:39899651 | DOI:10.1371/journal.pone.0317907

PLoS One. 2025 Feb 3;20(2):e0317734. doi: 10.1371/journal.pone.0317734. eCollection 2025.

ABSTRACT

INTRODUCTION: Chronic kidney disease (CKD) patients suffer from different comorbid conditions and are prone toward drug-related problems (DRPs) which affect their clinical parameters as well as quality of life (QoL). This study was aimed to evaluate the impact of clinical pharmacist-led interventions on the mean number of DRPs and the mean QoL score difference per patient DRPs in CKD patients.

METHOD: An open-labeled, randomized control trial performed from April 2023 to July 2023 in the nephrology unit of a tertiary care setting in Peshawar Pakistan. Those patients who met the inclusion criteria were randomized into two groups 1:1, i.e., control and intervention group. Clinical pharmacists identified the DRPs at baseline using Pharmaceutical Care Network Europe (PCNE) 9.1 guidelines. The QoL of patients were assessed at baseline and endpoint by using the Functional Assessment of Non-Life-Threatening Conditions (FANLTC) questionnaire.

RESULTS: A total of 100 patients were recruited having 50 in each group. The pharmacist identified a total of n = 230 DRPs in the intervention group, majority of the DRPs were attributed to inappropriate drug selection according to guidelines/formulary"; "inappropriate combinations of drugs or with herbal medications or dietary supplements"; and situations where "too many different drugs or active ingredients were prescribed". There was 46.52% reduction in the DRPs while comparing baseline and endpoint interventions suggested by pharmacist in the intervention group. The clinical pharmacist provided interventions in order to resolve the DRPs, and 37.40% interventions were accepted and fully implemented; 31.30% of the interventions were accepted and partially implemented. The clinical pharmacist identification and proposed intervention for DRPs contributed to a statistically significant improvement in QoL, from mean ± SD scored 58.64 ± 9.10 at the baseline to 74.48 ± 10.11 at the endpoint, with a p-value of < 0.001.

CONCLUSION: A significant improvement in the QoL and laboratory parameters for patients with CKD following clinical pharmacist-led interventions having proposed interventions were implemented successfully from baseline to endpoint; however, a considerable number of proposed interventions were not accepted and implemented.

PMID:39899613 | DOI:10.1371/journal.pone.0317734

Mol Divers. 2025 Feb 3. doi: 10.1007/s11030-025-11119-4. Online ahead of print.

ABSTRACT

Cancer remains one of the leading causes of death worldwide, with the rising incidence of breast cancer being a significant public health concern. Poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising therapeutic target for breast cancer treatment due to its crucial role in DNA repair. This study aimed to discover novel, targeted, and non-toxic PARP-1 inhibitors using an integrated approach that combines machine learning-based screening, molecular docking simulations, and quantum mechanical calculations. We trained a widely used machine learning models, Random Forest, using bioactivity data from known PARP-1 inhibitors. After evaluating the performance, it was used to screen an FDA-approved drug library, successfully identifying Atazanavir, Brexpiprazole, Raltegravir, and Nisoldipine as potential PARP-1 inhibitors. These compounds were further validated through molecular docking and all-atom molecular dynamics simulations, highlighting their potential for breast cancer therapy. The binding free energies indicated that Atazanavir at - 41.86 kJ/mol and Brexpiprazole at - 45.44 kJ/mol exhibited superior binding affinity compared to the control drug at - 30.42 kJ/mol, highlighting their promise as candidates for breast cancer therapy. Subsequent optimized geometries and electron density mappings of the two molecular structures revealed a Gibbs free energy of - 2334.610 Ha for the first molecule and - 1682.278316 Ha for the second, confirming enhanced stability compared to the standard drug. This study not only highlights the efficacy of machine learning in drug discovery but also underscores the importance of quantum mechanics in validating molecular stability, setting a robust foundation for future pharmacological explorations. Additionally, this approach could revolutionize the drug repurposing process by significantly reducing the time and cost associated with traditional drug development methods. Our results establish a promising basis for subsequent research aimed at optimizing these PARP-1 inhibitors for clinical use, potentially offering more effective treatment options for breast cancer patients.

PMID:39899126 | DOI:10.1007/s11030-025-11119-4

Heliyon. 2025 Jan 15;11(2):e41980. doi: 10.1016/j.heliyon.2025.e41980. eCollection 2025 Jan 30.

ABSTRACT

In light of the transition of COVID-19 from a pandemic to an endemic phase, there is still a dire need to address challenges associated with drug resistance, particularly among immunocompromised and high-risk populations. This review explores the current state of research on SARS-CoV-2 drug resistance and underscores the ongoing need for effective therapeutic strategies. It critically evaluates existing knowledge on resistance mechanisms and therapeutic options, aiming to consolidate information and highlight areas for future research. By examining the complex interactions between the virus and its host, the review advocates for a multifaceted approach, including combination therapies, targeted drug development, and continuous surveillance of viral mutations. It also emphasizes the impact of evolving viral variants on antiviral efficacy and suggests adaptive treatment protocols. This review aims to enhance our understanding of SARS-CoV-2 drug resistance and contribute to more effective management of COVID-19 through a discussion of promising strategies such as drug repurposing and combination therapies.

PMID:39897928 | PMC:PMC11786845 | DOI:10.1016/j.heliyon.2025.e41980

Targets (Basel). 2024 Dec;2(4):446-469. doi: 10.3390/targets2040025. Epub 2024 Dec 4.

ABSTRACT

Alzheimer's disease is a neurodegenerative disease that continues to have a rising number of cases. While extensive research has been conducted in the last few decades, only a few drugs have been approved by the FDA for treatment, and even fewer aim to be curative rather than manage symptoms. There remains an urgent need for understanding disease pathogenesis, as well as identifying new targets for further drug discovery. Alzheimer's disease (AD) is known to stem from a build-up of amyloid beta (Aβ) plaques as well as tangles of tau proteins. Furthermore, inflammation in the brain is known to arise from the degeneration of tissue and the build-up of insoluble material. Therefore, there is a potential link between the pathology of AD and inflammation in the brain, especially as the disease progresses to later stages where neuronal death and degeneration levels are higher. Proteins that are relevant to both brain inflammation and AD thus make ideal potential targets for therapeutics; however, the proteins need to be evaluated to determine which targets would be ideal for potential drug therapeutic treatments, or 'druggable'. Druggability analysis was conducted using two structure-based methods (i.e., Drug-Like Density analysis and SiteMap), as well as a sequence-based approach, SPIDER. The most druggable targets were then evaluated using single-nuclei sequencing data for their clinical relevance to inflammation in AD. For each of the top five targets, small molecule docking was used to evaluate which FDA approved drugs were able to bind with the chosen proteins. The top targets included DRD2 (inhibits adenylyl cyclase activity), C9 (binds with C5B8 to form the membrane attack complex), C4b (binds with C2a to form C3 convertase), C5AR1 (GPCR that binds C5a), and GABA-A-R (GPCR involved in inhibiting neurotransmission). Each target had multiple potential inhibitors from the FDA-approved drug list with decent binding infinities. Among these inhibitors, two drugs were found as top inhibitors for more than one protein target. They are C15H14N2O2 and v316 (Paracetamol), used to treat pain/inflammation originally for cataracts and relieve headaches/fever, respectively. These results provide the groundwork for further experimental investigation or clinical trials.

PMID:39897171 | PMC:PMC11786951 | DOI:10.3390/targets2040025

Int J Biol Sci. 2025 Jan 6;21(3):893-909. doi: 10.7150/ijbs.102461. eCollection 2025.

ABSTRACT

Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment. However, the underlying mechanism of NPC radioresistance remains poorly understood, and the promising radiosensitizer for NPC radiotherapy is also lacked. Overexpression of USP5 and EphA2 has been linked to various cancers, and both the proteins have attracted considerable attention for the development of new anti-cancer drugs. Here, we report that USP5 interacts with EphA2, and increases EphA2 protein stability and expression by ubiquitin proteasome pathway in the NPC cells. Mebendazole (MBZ), a broad-spectrum anthelmintic drug, transcriptionally inhibits USP5 expression, and then promotes EphA2 ubiquitination degradation in the NPC cells. Functionally, USP5 enhances in vitro and in vivo NPC cell radioresistance via stabilizing EphA2, and MBZ decreases in vitro and in vivo NPC cell radioresistance via targeting USP5/EphA2 axis. Moreover, the levels of USP5 and EphA2 are significantly higher in the radioresistant NPCs than those in the radiosensitive NPCs, and both proteins for predicting patient prognosis are superior to individual protein. These findings suggest that USP5 binds and stabilizes EphA2 by ubiquitin proteasome pathway to promote NPC radioresistance, and MBZ increases NPC radiosensitivity by targeting USP5/EphA2 axis, and is a potential radiosensitizer in NPC and perhaps in other cancers.

PMID:39897046 | PMC:PMC11781186 | DOI:10.7150/ijbs.102461

bioRxiv [Preprint]. 2025 Jan 21:2025.01.16.633410. doi: 10.1101/2025.01.16.633410.

ABSTRACT

Triple-negative breast cancer (TNBC), lacking expression of estrogen, progesterone, and HER2 receptors, is aggressive and lacks targeted treatment options. An RNA editing enzyme, adenosine deaminase acting on RNA 1 (ADAR1), has been shown to play important roles in TNBC tumorigenesis. We posit that ADAR1 functions as a homeostatic factor protecting TNBC from internal and external pressure, including metabolic stress. We tested the hypothesis that the iron- dependent cell death pathway, ferroptosis, is a ADAR1-protected metabolic vulnerability in TNBC by showing that ADAR1 knockdown sensitizes TNBC cells to GPX4 inhibitors. By performing single-reaction monitoring-based liquid chromatography coupled to mass spectrometry (LC-MS) to measure intracellular lipid contents, we showed that ADAR1 loss increased the abundance of polyunsaturated fatty acid phospholipids (PUFA-PL), of which peroxidation is the primary driver of ferroptosis. Transcriptomic analyses led to the discovery of the proto-oncogene MDM2 contributing to the lipid remodeling in TNBC upon ADAR1 loss. A phenotypic drug screen using a ferroptosis-focused library was performed to identify FDA- approved cobimetinib as a drug-repurposing candidate to synergize with ADAR1 loss to suppress TNBC tumorigenesis. By demonstrating that ADAR1 regulates the metabolic fitness of TNBC through desensitizing ferroptosis, we aim to leverage this metabolic vulnerability to inform basic, pre-clinical, and clinical studies to develop novel therapeutic strategies for TNBC.

PMID:39896528 | PMC:PMC11785053 | DOI:10.1101/2025.01.16.633410

J Pharm Anal. 2025 Jan;15(1):101084. doi: 10.1016/j.jpha.2024.101084. Epub 2024 Aug 27.

ABSTRACT

Protozoan infections (e.g., malaria, trypanosomiasis, and toxoplasmosis) pose a considerable global burden on public health and socioeconomic problems, leading to high rates of morbidity and mortality. Due to the limited arsenal of effective drugs for these diseases, which are associated with devastating side effects and escalating drug resistance, there is an urgent need for innovative antiprotozoal drugs. The emergence of drug repurposing offers a low-cost approach to discovering new therapies for protozoan diseases. In this review, we summarize recent advances in drug repurposing for various human protozoan diseases and explore cost-effective strategies to identify viable new treatments. We highlight the cross-applicability of repurposed drugs across diverse diseases and harness common chemical motifs to provide new insights into drug design, facilitating the discovery of new antiprotozoal drugs. Challenges and opportunities in the field are discussed, delineating novel directions for ongoing and future research.

PMID:39896318 | PMC:PMC11786068 | DOI:10.1016/j.jpha.2024.101084

Front Nutr. 2025 Jan 17;12:1524125. doi: 10.3389/fnut.2025.1524125. eCollection 2025.

ABSTRACT

Intermittent fasting has been linked to metabolic health by improving lipid profiles, reducing body weight, and increasing insulin sensitivity. However, several randomized clinical trials have shown that intermittent fasting is not more effective than standard daily caloric restriction for short-term weight loss or cardiometabolic improvements in patients with obesity. Observational studies also suggest cardiovascular benefits from extended rather than reduced eating windows, and indicate that long-term intermittent fasting regimens may increase the risk of cardiovascular disease mortality. In this perspective, we discuss evidence that may support potential adverse effects of intermittent fasting on cardiovascular health through the loss of lean mass, circadian misalignment and poor dietary choices associated with reward-based eating. Given the ongoing revolution in obesity pharmacotherapy, we argue that future research should integrate anti-obesity medications with dietary strategies that confer robust benefits to cardiometabolic health, combine exercise regimens, and consider genetic factors to personalize obesity treatment. Comprehensive approaches combining diet, pharmacotherapy, and lifestyle modifications will become crucial for managing obesity and minimizing long-term cardiovascular risk.

PMID:39895836 | PMC:PMC11782017 | DOI:10.3389/fnut.2025.1524125

Int J Qual Health Care. 2025 Feb 3:mzaf015. doi: 10.1093/intqhc/mzaf015. Online ahead of print.

ABSTRACT

BACKGROUND: Medications are a major cause of harm to patients in hospitals, and several studies have found that they cause approximately 20% of injuries that occur in medical institutions. It was found that the rate of adverse drug events (ADEs) in pediatric hospitalizations ranges from 11 to 40 events per 100 hospitalizations and 1% of cases caused death.Objectives: This is a comparative and retrospective study. The overarching objective is to adapt the Pediatric Trigger Tool (PTT) of the 'Child Health Corporation of America' to pediatric wards in Israel, with the intention of using it to assess the rate of adverse events that occur during medication given in pediatric wards. The study characterized ADEs and examined the ability of the PTT to identify ADEs in relation to those that were voluntarily reported by the staff.

METHOD: This study included internal and surgical pediatric wards at an academic pediatric medical center. The PTT was validated on medical record data from 700 hospitalizations between the years 2015 - 2017. The study also determined, among other things: the stage of drug administration at which the events occurred, the percentage of all events that could have been prevented, the degrees of damage the ADE caused and more.

RESULTS: The Positive Predictive Value (PPV) of the customized tool stands at 16.91%.The study found 108 ADEs in 78 hospitalizations. The ADE rate per 100 hospitalizations was 15.4, the ADE rate per 1,000 drug doses was 3.9, and the ADE rate per 1,000 hospitalization days was 22.8, of which 18.5% were preventable. The category of drugs that led to the highest number of ADEs was painkillers. Those ADEs led to a large number of adverse clinical effects: constipation, hypokalemia, vomiting, and rash. The most common reason for coming to the hospital was suspicion or treatment of a hematologic disease, followed by hospitalization due to a burn. The customized tool found 10.8 times more ADEs than those reported voluntarily-subjectively by the clinicalstaff.

CONCLUSIONS: The study found that, properly adapted, the PTT tool can be used to detectADEs in internal and surgical pediatric wards.

PMID:39898918 | DOI:10.1093/intqhc/mzaf015

Pediatr Pulmonol. 2025 Feb;60(2):e27491. doi: 10.1002/ppul.27491.

ABSTRACT

INTRODUCTION: The Cystic Fibrosis (CF) Foundation guideline for the treatment of pulmonary exacerbations (PEx) does not address empiric antibiotic selection. The primary objective of this study is to characterize how patient-specific microbiological histories are utilized in initial antibiotic selection for CF-related PEx at a pediatric institution. The secondary outcome was to characterize why changes were made to empiric antibiotic regimens.

METHODS: This single-center, retrospective study evaluated individuals aged 1-21 years hospitalized for CF-related PEx at Children's Medical Center Dallas between August 1, 2016 and July 31, 2018.

RESULTS: Among 285 screened hospital encounters, 156 encounters met inclusion criteria. Median age was 12.9 years with a median baseline forced expiratory volume (FEV1) of 84% predicted. Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia were the organisms most targeted by empiric antibiotics with median months since last growth of 1.5, 9.2, and 5.5, respectively. A difference was observed in median time since last growth for targeted organisms versus those not targeted by the initial antibiotics, but wide overlapping timeframes were noted. Organisms isolated on admission cultures were sensitive to the initial antibiotics regimen in 78.2% of encounters.

CONCLUSION: While variable, patient-specific microbiologic history and time since last growth of historical organisms are taken into consideration when selecting initial antibiotics for the treatment of PEx in children with CF. Expanding initial antibiotic coverage to target microbiological growth histories beyond 1 year prior to a hospital admission did not appear to increase the likelihood of providing coverage for organism(s) isolated on the admission sputum culture in children hospitalized for CF-related PEx.

PMID:39898731 | DOI:10.1002/ppul.27491

Pediatr Pulmonol. 2025 Feb;60(2):e27506. doi: 10.1002/ppul.27506.

ABSTRACT

BACKGROUND: CF R.I.S.E is a program that helps people with Cystic Fibrosis (pwCF) transition from pediatric to adult care. In 2022, we adapted it to CF S.O.B.E in Turkish during a training session. This project aims to present the results of the CF S.O.B.E program.

METHODS: This study included 81 pwCF aged 16-25, divided into two groups: the standard CF S.O.B.E. group (n = 39) and the modified group (n = 42). The standard group received face-to-face education. Both groups participated in online training sessions and received written materials. The knowledge levels were evaluated with Knowledge Assessment Questionnaires (KAQ).

RESULTS: The standard group showed higher post-training scores in "Lung Health and Airway Clearance" and "Equipment Maintenance and Infection Control" (p = 0.014 and 0.002). Modified group showed improvements in all KAQs except "Lung Health and Airway Clearance", "CF-related Liver Disease," "Pancreatic Insufficiency and Nutrition," and "Male Sexual Health." Regarding Pancreatic Insufficiency & Nutrition and CF-related Diabetes, individuals with these conditions demonstrated higher pretest scores than those without these conditions (p = 0.01 and 0.002, respectively). Both groups and their parents reported high satisfaction, and healthcare providers endorsed the program's effectiveness.

CONCLUSION: Our study demonstrated the CF S.O.B.E program's success in enhancing knowledge, disease management skills, and self-confidence among pwCF. While the modified CF S.O.B.E program may be suitable for resource-limited centers, the priority should be to implement the standard program due to its superior outcomes in self-confidence and disease management. This study lays the foundation for incorporating CF S.O.B.E as a standard practice and evaluating its long-term clinical impact.

PMID:39898696 | DOI:10.1002/ppul.27506

Pediatr Pulmonol. 2025 Feb;60(2):e27510. doi: 10.1002/ppul.27510.

NO ABSTRACT

PMID:39898620 | DOI:10.1002/ppul.27510