bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness, nephrotoxicity, and therapeutic drug monitoring of polymyxin B in nosocomial pneumonia among critically ill patients
Authors: Ye Qinghua , Wang Qianlin , Chen Ziying , Chen Wenqian , Zhan Qingyuan , Wang Chen 
Published: May 2022

AbstractObjectivesWe aimed to assess the effectiveness and nephrotoxicity of polymyxin B in critically ill patients with nosocomial pneumonia and to evaluate the utility of its therapeutic drug monitoring (TDM).MethodsWe retrospectively analyzed patients who received polymyxin B treatment for ≥48 h since the establishment of polymyxin B TDM in a 26‐bed tertiary referral intensive care unit. Univariate and multivariate analyses were conducted to assess the variables associated with polymyxin B effectiveness and nephrotoxicity.ResultsA total of 62 patients were enrolled. Most (56.5%) of the patients performed TDM, 54.3% of them reached the therapeutic target of area under curve across 24 h at steady state (AUCss,24h) of 50–100 mg h L−1, and 10 patients had an AUCss,24h value of <50 mg h L−1. Thirty‐six (58.1) and 31 (50.0%) patients had favorable clinical and microbiological responses, respectively. Reaching the therapeutic target of AUCss,24h (odds ratio [OR] = 13.15, p = 0.015), a favorable microbiological response (OR = 40.80, p = 0.00), and complicated with septic shock (OR = 0.12, p = 0.021) were independently associated with favorable clinical outcomes of polymyxin B treatment. The incidence of acute kidney injury (AKI) was 45.2%. A lower creatinine clearance (OR = 0.96, p = 0.008) and concomitant treatment with loop diuretics (OR = 5.93, p = 0.046) were predictive of nephrotoxicity.ConclusionOur findings show that TDM of polymyxin B is a valuable intervention, and the achievement of its optimal pharmacodynamic target can improve treatment outcome. Renal insufficiency and concomitant treatment with loop diuretics were found to be associated with the risk of nephrotoxicity.
Pharmacokinetics of vaginal versus buccal misoprostol for labor induction at term
Authors: Vorontsova Yana , Haas David M. , Flannery Kathleen , Masters Andrea R. , Silva Larissa L. , Pierson Rebecca C. , Yeley Brittany , Hogg Graham , Guise David , Heathman Michael , Quinney Sara K. 
Published: May 2022

AbstractThe IMPROVE study (NCT02408315) compared the efficacy and safety of vaginal and buccal administration of misoprostol for full‐term, uncomplicated labor induction. This report compares the pharmacokinetics of misoprostol between vaginal and buccal routes. Women greater than or equal to 14 years of age undergoing induction of labor greater than or equal to 37 weeks gestation without significant complications were randomized to vaginal or buccal misoprostol 25 μg followed by 50 μg doses every 4 h. Misoprostol acid concentrations were determined using liquid chromatography‐tandem mass spectrometry for the first 8 h in a subgroup of participants. A population pharmacokinetic model was developed using NONMEM. Plasma concentrations (n = 469) from 47 women were fit to a one‐compartment nonlinear clearance model. The absorption rate constant (ka) was dependent on both route and dose of administration: buccal 25 μg 0.724 (95% confidence interval, 0.54–0.92) h−1; 50 μg 0.531 (0.37–0.63) h−1; vaginal 25 μg 0.507 (0. 2–1. 4) h−1; and 50 μg 0.246 (0.103–0.453) h−1. Relative bioavailability for vaginal compared to buccal route was 2.4 (1.63–4.77). There was no effect of body mass index or age on apparent clearance 705 (431–1099) L/h or apparent volume of distribution 632 (343–1008) L. The area under the concentration–time curve to 4 h following the first 25 μg dose of misoprostol was 16.5 (15.4–17.5) pg h/ml for buccal and 34.3 (32.5–36.1) pg h/ml for vaginal administration. The rate of buccal absorption was two times faster than that of vaginal, whereas bioavailability of vaginal administration was 2.4 times higher than that of buccal. Decreased time to delivery observed with vaginal dosing may be due to higher exposure to misoprostol acid compared to buccal.
Evolution of preclinical characterization and insights into clinical pharmacology of checkpoint inhibitors approved for cancer immunotherapy
Authors: Kasichayanula Sreeneeranj , Mandlekar Sandhya , Shivva Vittal , Patel Maulik , Girish Sandhya 
Published: May 2022

AbstractCancer immunotherapy has significantly advanced the treatment paradigm in oncology, with approvals of immuno‐oncology agents for over 16 indications, many of them first line. Checkpoint inhibitors (CPIs) are recognized as an essential backbone for a successful anticancer therapy regimen. This review focuses on the US Food and Drug Administration (FDA) regulatory approvals of major CPIs and the evolution of translational advances since their first approval close to a decade ago. In addition, critical preclinical and clinical pharmacology considerations, an overview of the pharmacokinetic and dose/regimen aspects, and a discussion of the future of CPI translational and clinical pharmacology as combination therapy becomes a mainstay of industrial immunotherapy development and in clinical practice are also discussed.
Canagliflozin and atrial fibrillation in type 2 diabetes mellitus: A secondary analysis from the CANVAS Program and CREDENCE trial and meta‐analysis
Authors: Li Chao , Yu Jie , Hockham Carinna , Perkovic Vlado , Neuen Brendon L. , Badve Sunil V. , Houston Lauren , Lee Vivian Y. J. , Barraclough Jennifer Y. , Fletcher Robert A. , Mahaffey Kenneth W. , Heerspink Hiddo J. L. , Cannon Christopher P. , Neal Bruce , Arnott Clare 
Published: May 2022

AbstractAimTo assess the effects of canagliflozin on the incidence of atrial fibrillation/atrial flutter (AF/AFL) and other key cardiorenal outcomes in a pooled analysis of the CANVAS and CREDENCE trials.Materials and MethodsParticipants with type 2 diabetes and high risk of cardiovascular disease or chronic kidney disease were included and randomly assigned to canagliflozin or placebo. We explored the effects of canagliflozin on the incidence of first AF/AFL events and AF/AFL‐related complications (ischaemic stroke/transient ischaemic attack/hospitalization for heart failure). Major adverse cardiovascular events and a renal‐specific outcome by baseline AF/AFL status were analysed using Cox regression models.ResultsOverall, 354 participants experienced a first AF/AFL event. Canagliflozin had no detectable effect on AF/AFL (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.67‐1.02) compared with placebo. Subgroup analysis, however, suggested a possible reduction in AF/AFL in those with no AF/AFL history (HR 0.78, 95% CI 0.62‐0.99). Canagliflozin was also associated with a reduction in AF/AFL‐related complications (HR 0.74, 95% CI 0.65‐0.86). There was no evidence of treatment heterogeneity by baseline AF/AFL history for other key cardiorenal outcomes (all Pinteraction > 0.14). Meta‐analysis of five sodium‐glucose cotransporter‐2 (SGLT2) inhibitor trials demonstrated a 19% reduction in AF/AFL events with active treatment (HR 0.81, 95% CI 0.72‐0.92).ConclusionsOverall, a significant effect of canagliflozin on the incidence of AF/AFL events could not be shown, however, a possible reduction in AF/AFL events in those with no prior history requires further investigation. Meta‐analysis suggests SGLT2 inhibition reduces AF/AFL incidence.
Liquid fluorophore taggants for mark‐release‐recapture research: a survey of potential arthropod targets
Authors: Hagler James R. , Casey Miles T. , Hull Allya M. , Machtley Scott A. 
Published: May 2022

AbstractWe evaluated a method for marking arthropods that could serve as a valuable tool for mark‐release‐recapture dispersal research. The taggants tested consisted of three liquid fluorophores labeled cartax green, magenta, and orange. The manufacturer markets these fluorescent markers as forensic theft deterrents. Specimens of 16 genera of arthropods were externally marked with either one of the colored fluorophores or with water (negative control treatment). The specimens were then qualitatively and quantitatively inspected for fluorescence 24 h later. For the qualitative analysis, three independent observers scored each specimen by direct observation for the presence of a fluorescent mark. The specimens were scored using a portable ultraviolet (UV) tube lantern and a specialized NIGHTSEA‐brand LED UV light. The three fluorophores were readily detected on many but not all the species examined, regardless of the type of UV light used. Moreover, the NIGHTSEA LED light yielded fewer false‐negative observer errors than the lantern. Each specimen's fluorescence was measured with an automated dual‐wavelength microplate fluorometer for the quantitative analysis. Overall, the quantitative analysis was very reliable at detecting fluorescence on a few taxa [e.g.,Bemisia tabaci(Gennadius) (Hemiptera: Aleyrodidae),Chrysoperlaspp. (Neuroptera: Chrysopidae)], effective on most taxa, and unreliable on several others [e.g.,Collops vittatus(Say) (Coleoptera: Melyridae),Geocorisspp. (Hemiptera: Geocoridae),Mecaphesa celer(Hentz) (Araneae: Thomisidae)]. The cartax green marker was more readily detected than the magenta and orange markers with both visual and automated detection. Overall, the results show that these fluorophores could be effective markers for many arthropod species.
Clinical characteristics and long‐term outcome of cerebral cavernous malformations‐related epilepsy
Authors: Shih Yen‐Cheng , Chou Chien‐Chen , Peng Syu‐Jyun , Yu Hsiang‐Yu , Hsu Sanford P. C. , Lin Chun‐Fu , Lee Cheng‐Chia , Yang Huai‐Che , Chen Yi‐Chieh , Kwan Shang‐Yeong , Chen Chien , Wang Shuu‐Jiun , Lin Chung‐Jung , Lirng Jiing‐Feng , Shih Yang‐Hsin , Yen Der‐Jen , Liu Yo‐Tsen 
Published: May 2022

AbstractObjectiveCerebral cavernous malformations (CCMs) present variably, and epileptic seizures are the most common symptom. The factors contributing to cavernoma‐related epilepsy (CRE) and drug resistance remain inconclusive. The outcomes of CRE after different treatment modalities have not yet been fully addressed. This study aimed to characterize the clinical features of patients with CRE and the long‐term seizure outcomes of medical and surgical treatment strategies.MethodsThis was a retrospective cohort of 135 patients with CCM who were diagnosed in 2007–2011 and followed up for 93.6 months on average. The patients were divided into drug‐resistant epilepsy (DRE;n = 29), non‐DRE (n = 45), and no epilepsy (NE;n = 61).ResultsTemporal CCM was the factor most strongly associated with the development of both CRE and DRE. The majority of patients with single temporal CCMs had CRE (86.8%,n = 33), and 50% had DRE, whereas only 14.7% (n = 5) with a nontemporal supratentorial CCM had DRE (p < .05). The most common lesion site in the DRE group was the mesiotemporal lobe (50%). Multiple CCMs were more frequently observed in the CRE (29.2%) than the NE (11.5%) group (p < .05). In patients with CRE, multiple lesions were associated with a higher rebleeding rate (odds ratio = 11.1), particularly in those with DRE (odds ratio = 15.4). The majority of patients who underwent resective surgery for DRE (76.5%,n = 13) achieved International League Against Epilepsy Class I and II seizure outcomes even after a long disease course.SignificanceTemporal CCM not only predisposes to CRE but also is a major risk factor for drug resistance. The mesiotemporal lobe is the most epileptogenic zone. Multiple CCMs are another risk factor for CRE and increase the rebleeding risk in these patients. Surgical resection could provide beneficial long‐term seizure outcomes in patients with DRE.
Detection rate and variables associated with incidental prostate cancer by holmium laser enucleation of the prostate
Authors: Banno Taro , Nakamura Kazutaka , Kaneda Yudai , Ozaki Akihiko , Kouchi Yukiko , Ohira Tadashi , Shimmura Hiroaki 
Published: May 2022

ObjectivesHolmium laser enucleation of the prostate is well‐established and effective for bladder outlet obstruction due to benign prostatic hyperplasia. The objective of this study was to examine the detection rate of incidental prostate cancer by holmium laser enucleation of the prostate and variables associated with them.MethodsA total of 612 patients were enrolled. We retrospectively examined the detection rate of incidental prostate cancer and perioperative variables associated with them.ResultsForty‐nine of 612 patients were diagnosed with incidental prostate cancer. Univariate logistic regression analysis showed that higher prostate‐specific antigen density (odds ratio 3.34, 95% confidence interval 1.02–10.94, P = 0.05), higher prostate‐specific antigen density of the transition zone (odds ratio 2.28, 95% confidence interval 1.02–5.09, P = 0.04), and findings of the prostate cancer on magnetic resonance imaging (peripheral zone: odds ratio 4.71, 95% confidence interval 1.70–13.1, P = 0.003; transition zone: odds ratio 3.46, 95% confidence interval 1.74–6.86, P < 0.001; peripheral and transition zones: odds ratio 6.00, 95% confidence interval 1.51–23.8, P = 0.01) were significantly associated with incidental prostate cancer. Multivariate logistic regression analysis showed that findings of the prostate cancer on magnetic resonance imaging (peripheral zone: odds ratio 4.36, 95% confidence interval 1.49–12.8, P = 0.001; transition zone: odds ratio 3.54, 95% confidence interval 1.75–7.16, P < 0.001; peripheral and transition zones: odds ratio 6.14, 95% confidence interval 1.53–24.5, P = 0.01) was an independent risk factor for incidental prostate cancer.ConclusionThe detection rate of incidental prostate cancer was 8.0%, and findings of the prostate cancer on magnetic resonance imaging were an independent predictive factor for incidental prostate cancer.
Potential of propolis antifungal activity for clinical applications
Authors: Cerqueira Patrícia , Cunha Ana , Almeida-Aguiar Cristina 
Published: May 2022

AbstractThe high incidence of skin diseases of microbial origin along with the widespread increase of microbial resistance demand for therapeutic alternatives. Research on natural compounds has been opening new perspectives for the development of new therapies with health-positive impacts. Propolis, a resinous mixture produced by honeybees from plant exudates, is widely used as a natural medicine since ancient times, mainly due to its antimicrobial properties. More recently, antioxidant, anti-tumour, anti-inflammatory, hepatoprotective and immunomodulatory activities were also reported for this natural product, highlighting its high potential pharmacological interest. In the present work, an extensive review of the main fungi causing skin diseases as well as the effects of natural compounds, particularly propolis, against such disease-causing micro-organisms was organized and compiled in concise handy tables. This information allows to conclude that propolis is a highly effective antimicrobial agent suggesting that it could be used as an alternative skin treatment against pathogenic micro-organisms and also as a cosmeceutical component or as a source of bioactive ingredients.
Delineation of blacktip shark (Carcharhinus limbatus) nursery habitats in the north‐western Gulf of Mexico
Authors: Matich Philip , Bigelow Camryn L. , Chambers Barrett , Dodds Jillian J. , Hebert Jessica A. , Lemieux Alexis , Pittman Christy M. , Trapp Julianna , Bianco Brooke , Cadena Carolina P. , Castillo Emily I. , Castillo Gabriela I. , Dawdy Alexandra , Dominguez Alina I. , Dominique Nicholas , French Donavon R. , Glenn Callie F. , Jackson Elena C. H. , Johnson Breidon , Kohl Gunnar , Manka Cameron , Martin Jared K. , Pappas Matthew , Reedholm Audrey J. , Snead Kailey M. , Tyree Matthew K. , Fisher Mark 
Published: May 2022

AbstractCoevolution with predators leads to the use of low‐risk habitats by many prey species, which promotes survival during early developmental phases. These nurseries are valued by conservation and management agencies because of their contributions to adult populations. However, the physical and geographic characteristics, like shallow depths and isolation from other marine habitats, that restrict access to predators and thereby reduce risk to juvenile animals can also limit scientific research. Consequently, many nursery habitats are still unidentified and understudied. Here we used gillnet monitoring from 1982 to 2018 to delineate blacktip shark (Carcharhinus limbatus) nurseries in the north‐western Gulf of Mexico and elucidated their physical, environmental and biological characteristics. Nursery habitats within estuaries (<2% of spatial area) were proximate to the Gulf of Mexico and exhibited significantly lower variability in salinity than non‐nurseries. However, relative abundances of predators and prey were not significant delineators of nursery habitats. As such, food and risk may not influence juvenile blacktip habitat use as expected. Alternatively, reduced osmoregulatory stress attributed to predictable environments likely provides advantageous conditions for blacktips to develop foraging and antipredator tactics, which is vital prior to the winter migration of juvenile sharks into the Gulf of Mexico.
Preparation, characterization, and evaluation of anti‐tyrosinase activity of solid lipid nanoparticles containing Undecylenoyl phenylalanine (Sepiwhite®)
Authors: Kabiri Homa , Tayarani‐Najaran Zahra , Rahmanian‐devin Pouria , Vaziri Mohadeseh Sadat , Nasirizadeh Samira , Golmohammadzadeh Shiva , Kamali Hossein 
Published: May 2022

AbstractBackgroundHyperpigmentation is darkened patches or spots on the skin occurred by increased melanin. Undecylenoyl phenylalanine (Sepiwhite®), as a commercial lipophilic derivative of phenylalanine, is a powerful new brightener that can be used in the treatment of skin pigmentation disorders.AimsSolid lipid nanoparticles (SLNs) increase the efficiency of hydrophobic drugs. The current study aimed to prepare and characterize SLNs containing Sepiwhite (SEPI‐SLN).MethodsIn this study, an optimized SEPI‐SLN formulation was selected by applying the response surface method. In vitro drug loading content, the release profile of SEPI, and cell viability were investigated. The permeation rate of SEPI‐SLN was also compared to conventional cream containing Sepiwhite (SEPI‐CREAM). Furthermore, the anti‐tyrosinase activity of Sepiwhite was also evaluated.ResultsThe optimized formulation showed a spherical morphology with particle size and entrapment efficiency of 218.6 ± 11.1 nm and % 87.31 ± 0.65, respectively. Differential scanning calorimetry (DSC) analysis confirmed SEPI‐loaded SLN formulation with no drug‐lipid incompatibility. The in vitro permeation experiment revealed the enhanced cutaneous uptake of SEPI‐SLN. The results also showed that Sepiwhite could stop melanogenesis with inhibition of the tyrosinase enzyme.ConclusionOur findings confirm that SLNs could be a proper nanocarrier for the relevant usage of Sepiwhite as a powerful brightener agent.
A rapid evidence assessment of sickle cell disease educational interventions
Authors: Oti Anthonia Etonlogbo , Heyes Kim , Bruce Faye , Wilmott Danita 
Published: May 2022

AbstractAims and objectivesTo assess the impact of educational interventions on the knowledge and attitude of healthcare professionals (HCPs) regarding sickle cell disease (SCD) pain management in the UK.BackgroundVariations and inadequate pain management due toHCPs’ lack of knowledge and negative attitude is still an ongoing global concern for SCD patients despite availability of effective treatment and evidence‐based guidelines. Several international studies have implemented interventions aimed at improving knowledge, attitude, and pain management. No review on the effectiveness of these interventions was found. Also, no previous intervention done in the UK was found from the thorough search of research databases. However, there are estimated 240,000 genetic carriers with about 12,500–15,000 estimated people living with SCD in the UK.DesignRapid Evidence Assessment of existing evidence.MethodsA rapid evidence assessment was conducted between March 2021–January 2022 following the PRISMA 2020 guidelines. Included papers must have an educational intervention about SCD or related symptom management where the learners were HCPs. Excluded papers were those not published in English or before 2010. The following databases were searched: CINAHL, MEDLINE, PubMed America and Europe, Scopus, PsycINFO and Web of Science. Data quality was assessed using the Mixed Methods Assessment Tool (MMAT) and analysed using a narrative approach.ResultsTen studies were included in the final review. Overall, they reported improved outcomes in six main themes: knowledge, attitude, perception, adoption, satisfaction and efficiency. Five studies reported statistically significant improvement in at least one outcome, four studies reported positive improvement, and two studies reported no significant improvement in knowledge and attitude. These heterogeneous studies were implemented once, and all designs were prone to bias; this makes it difficult to state how effective interventions are for SCD.ConclusionCurrent evidence of positive improvement in HCPs’ knowledge and attitude is insufficient for generalisation and recommendation for adoption. However, we believe that implementing validated educational interventions remains essential for effective acute SCD pain management and patient‐centred care. Further research is needed to find a suitable educational intervention that can be replicated.Relevance to clinical practiceQuality SCD education, timely crisis management and reduced patient stigma are crucial in reducing the risk of rapid clinical decompensation to avoid developing life‐threatening complications. Understanding SCD can also support the building of therapeutic relationships between the patient and practitioner.Trial registrationThis review was not registered.
ASNM and ASN joint guidelines for transcranial Doppler ultrasonic monitoring: An update
Authors: Razumovsky Alexander Y. , Jahangiri Faisal R. , Balzer Jeffrey , Alexandrov Andrei V. 
Published: May 2022

AbstractToday, it seems prudent to reconsider how ultrasound technology can be used for providing intraoperative neurophysiologic monitoring that will result in better patient outcomes and decreased length and cost of hospitalization. An extensive and rapidly growing literature suggests that the essential hemodynamic information provided by transcranial Doppler (TCD) ultrasonography neuromonitoring (TCDNM) would provide effective monitoring modality for improving outcomes after different types of vascular, neurosurgical, orthopedic, cardiovascular, and cardiothoracic surgeries and some endovascular interventional or diagnostic procedures, like cardiac catheterization or cerebral angiography. Understanding, avoiding, and preventing peri‐ or postoperative complications, including neurological deficits following abovementioned surgeries, endovascular intervention, or diagnostic procedures, represents an area of great public and economic benefit for society, especially considering the aging population. The American Society of Neurophysiologic Monitoring and American Society of Neuroimaging Guidelines Committees formed a joint task force and developed updated guidelines to assist in the use of TCDNM in the surgical and intensive care settings. Specifically, these guidelines define (1) the objectives of TCD monitoring; (2) the responsibilities and behaviors of the neurosonographer during monitoring; (3) instrumentation and acquisition parameters; (4) safety considerations; (5) contemporary rationale for TCDNM; (6) TCDNM perspectives; and (7) major recommendations.