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1.
Eur J Heart Fail ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837516

ABSTRACT

AIMS: Heart failure (HF) elicits a pro-inflammatory state, which is associated with impaired clinical outcomes, but no anti-inflammatory therapies have demonstrated a clinical benefit yet. Inflammatory pathways related with the interleukin-1 axis are overactivated during episodes of acute HF. Colchicine, an anti-inflammatory drug with proven benefits in acute pericarditis and ischaemic heart disease, may target this inflammatory response. This study aims to assess the efficacy of colchicine in acute HF patients. METHODS: COLICA is a multicentre, randomized, double-blind, placebo-controlled trial enrolling 278 patients across 12 sites. Patients presenting with acute HF, clinical evidence of congestion requiring ≥40 mg of intravenous furosemide and N-terminal pro-B-type natriuretic peptide (NT-proBNP) >900 pg/ml, are eligible for participation. Patients are enrolled irrespective of left ventricular ejection fraction, HF type (new-onset or not) and setting (hospital or outpatient clinic). Patients are randomized 1:1 within the first 24 h of presentation to either placebo or colchicine, with an initial loading dose of 2 mg followed by 0.5 mg every 12 h for 8 weeks (reduced dose if <70 kg, >75 years old, or glomerular filtration rate <50 ml/min/1.73 m2). The primary efficacy endpoint is the time-averaged proportional change in NT-proBNP concentrations from baseline to week 8. Key secondary and exploratory outcomes include symptoms, diuretic use, worsening HF episodes, related biomarkers of cardiac stress and inflammation, total and cardiovascular readmissions, mortality and safety events. CONCLUSION: COLICA will be the first randomized trial testing the efficacy and safety of colchicine for acute HF.

2.
Sensors (Basel) ; 24(11)2024 May 31.
Article in English | MEDLINE | ID: mdl-38894355

ABSTRACT

This paper presents the results of a study on data preprocessing and modeling for predicting corrosion in water pipelines of a steel industrial plant. The use case is a cooling circuit consisting of both direct and indirect cooling. In the direct cooling circuit, water comes into direct contact with the product, whereas in the indirect one, it does not. In this study, advanced machine learning techniques, such as extreme gradient boosting and deep neural networks, have been employed for two distinct applications. Firstly, a virtual sensor was created to estimate the corrosion rate based on influencing process variables, such as pH and temperature. Secondly, a predictive tool was designed to foresee the future evolution of the corrosion rate, considering past values of both influencing variables and the corrosion rate. The results show that the most suitable algorithm for the virtual sensor approach is the dense neural network, with MAPE values of (25 ± 4)% and (11 ± 4)% for the direct and indirect circuits, respectively. In contrast, different results are obtained for the two circuits when following the predictive tool approach. For the primary circuit, the convolutional neural network yields the best results, with MAPE = 4% on the testing set, whereas for the secondary circuit, the LSTM recurrent network shows the highest prediction accuracy, with MAPE = 9%. In general, models employing temporal windows have emerged as more suitable for corrosion prediction, with model performance significantly improving with a larger dataset.

3.
J Infect ; 89(2): 106197, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38879134

ABSTRACT

Implant-based reconstructions are increasingly utilized following mastectomy in the prevention and treatment of breast cancer. However, these implants are associated with a high rate of infection, which is a major complication that can lead to implant removal, delay in adjuvant radiation and chemotherapy, and increase in health care costs. Early clinical signs and symptoms of infection, such as erythema, warmth, and tenderness, are challenging to discern from expected postsurgical responses. Furthermore, when atypical features are present or the patient's condition does not improve on adequate antimicrobials, the clinician should be prompted to consider an alternative noninfectious etiology. Herein we highlight the key elements of the preventive, diagnostic, and multidisciplinary therapeutic approach to salvaging the infected breast implant; review several infectious disease mimickers; and provide many pearls of wisdom that the practicing clinician must be familiar with and be able to manage in an effective and successful manner.

4.
Tex Heart Inst J ; 51(1)2024 May 15.
Article in English | MEDLINE | ID: mdl-38748549

ABSTRACT

BACKGROUND: Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. METHODS: A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. RESULTS: Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). CONCLUSION: No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.


Subject(s)
Anticoagulants , Obesity , Venous Thromboembolism , Warfarin , Humans , Retrospective Studies , Female , Male , Warfarin/adverse effects , Warfarin/administration & dosage , Warfarin/therapeutic use , Obesity/complications , Anticoagulants/adverse effects , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Middle Aged , Venous Thromboembolism/epidemiology , Venous Thromboembolism/drug therapy , Administration, Oral , Aged , Treatment Outcome , Factor Xa Inhibitors/adverse effects , Factor Xa Inhibitors/administration & dosage , Factor Xa Inhibitors/therapeutic use , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Follow-Up Studies
5.
JMIR Form Res ; 8: e53000, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38621237

ABSTRACT

BACKGROUND: The syndemic nature of gonococcal infections and HIV provides an opportunity to develop a synergistic intervention tool that could address the need for adequate treatment for gonorrhea, screen for HIV infections, and offer pre-exposure prophylaxis (PrEP) for persons who meet the criteria. By leveraging information available on electronic health records, a clinical decision support (CDS) system tool could fulfill this need and improve adherence to Centers for Disease Control and Prevention (CDC) treatment and screening guidelines for gonorrhea, HIV, and PrEP. OBJECTIVE: The goal of this study was to translate portions of CDC treatment guidelines for gonorrhea and relevant portions of HIV screening and prescribing PrEP that stem from a diagnosis of gonorrhea as an electronic health record-based CDS intervention. We also assessed whether this CDS solution worked in real-world clinic. METHODS: We developed 4 tools for this CDS intervention: a form for capturing sexual history information (SmartForm), rule-based alerts (best practice advisory), an enhanced sexually transmitted infection (STI) order set (SmartSet), and a documentation template (SmartText). A mixed methods pre-post design was used to measure the feasibility, use, and usability of the CDS solution. The study period was 12 weeks with a baseline patient sample of 12 weeks immediately prior to the intervention period for comparison. While the entire clinic had access to the CDS solution, we focused on a subset of clinicians who frequently engage in the screening and treatment of STIs within the clinical site under the name "X-Clinic." We measured the use of the CDS solution within the population of patients who had either a confirmed gonococcal infection or an STI-related chief complaint. We conducted 4 midpoint surveys and 3 key informant interviews to quantify perception and impact of the CDS solution and solicit suggestions for potential future enhancements. The findings from qualitative data were determined using a combination of explorative and comparative analysis. Statistical analysis was conducted to compare the differences between patient populations in the baseline and intervention periods. RESULTS: Within the X-Clinic, the CDS alerted clinicians (as a best practice advisory) in one-tenth (348/3451, 10.08%) of clinical encounters. These 348 encounters represented 300 patients; SmartForms were opened for half of these patients (157/300, 52.33%) and was completed for most for them (147/300, 89.81%). STI test orders (SmartSet) were initiated by clinical providers in half of those patients (162/300, 54%). HIV screening was performed during about half of those patient encounters (191/348, 54.89%). CONCLUSIONS: We successfully built and implemented multiple CDC treatment and screening guidelines into a single cohesive CDS solution. The CDS solution was integrated into the clinical workflow and had a high rate of use.

6.
Diagn Microbiol Infect Dis ; 109(1): 116246, 2024 May.
Article in English | MEDLINE | ID: mdl-38452556

ABSTRACT

Providencia rettgeri, belonging to the genus Providencia, had gained significant interest due to its increasing prevalence as a common pathogen responsible for healthcare-associated infections in hospitals. P. rettgeri isolates producing carbapenemases have been reported to reduce the efficiency of carbapenems in clinical antimicrobial therapy. However, coexistence with other resistance determinants is rarely reported. The goal of this study was the molecular characterization of carbapenemase-producing Providencia spp. clinical isolates. Among 23 Providencia spp. resistant to imipenem, 21 were positive to blaNDM-1; one positive to blaNDM-1 and blaOXA-58 like; and one isolate co-producing blaIMP-27, blaOXA-24/40 like, and blaOXA-58 like were identified. We observed a low clonal relationship, and the incompatibility groups Col3M and ColRNAI were identified in the plasmid harboring blaNDM-1. We report for the first time a P. rettgeri strain co-producing blaIMP-27, blaOXA-24-like, and blaOXA-58 like. The analysis of these resistance mechanisms in carbapenemase co-producing clinical isolates reflects the increased resistance.


Subject(s)
Anti-Bacterial Agents , Providencia , Humans , Anti-Bacterial Agents/pharmacology , Providencia/genetics , Mexico/epidemiology , Microbial Sensitivity Tests , beta-Lactamases/genetics , Bacterial Proteins/genetics
7.
Anthropol Anz ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500366

ABSTRACT

This study analyzed the paleopathological conditions of a 30-year-old male unearthed at the site of Ya'amun in northern Jordan. The skeleton was dated back to Iron age. The paleopathological examinations were performed using macroscopic and radiological analyses. The results revealed multiple significant bone lesions, including periosteal osteosarcoma of the right femur, plagiocephaly, asymmetry of the sacrum, vertebral fractures, anemia, and osteoarthritis. This case represents the first example of neoplasm and plagiocephaly in the Iron Age of the region. Despite enduring severe health conditions, the individual managed to reach the third decade while facing the demands of strenuous daily activities that exemplified the harsh living and subsistence conditions characteristic of the Iron Age.

8.
Animals (Basel) ; 14(5)2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38473127

ABSTRACT

A retrospective study of microbiological laboratory results from 2020 to 2022, obtained from a veterinary diagnostic laboratory of the island of Gran Canaria, Spain, focused on canine otitis cases, was performed. The objective of this study was to analyze the pathogen distribution, antimicrobial susceptibility, prevalence of multidrug resistant phenotypes and the role of coinfections in otitis cases in order to provide up-to-date evidence that could support effective control strategies for this prevalent pathology. A total of 604 submissions were processed for the diagnosis of canine external otitis. Of the samples analyzed, 472 were positive for bacterial or fungal growth (78.1%; 95% CI: 74.8-81.4%). A total of 558 microbiological diagnoses were obtained, divided in 421 bacterial (75.4%; 95% CI: 71.8-79.0%) and 137 fungal (24.6%; 95% CI: 20.9-28.1%) identifications. Staphylococcus pseudintermedius, Malassezia pachydermatis and Pseudomonas aeruginosa were the most prevalent microorganisms detected in clinical cases of otitis. High level antimicrobial resistance was found for Pseudomonas aeruginosa (30.7%), Proteus mirabilis (29.4%), Staphylococcus pseudintermedius (25.1%) and Escherichia coli (19%). Multidrug-resistant phenotypes were observed in 47% of the bacteria isolated. In addition, a 26.4% prevalence of methicillin-resistant Staphylococcus pseudintermedius was detected. The high prevalence of antimicrobial resistant phenotypes in these bacteria highlights the current necessity for constant up-to-date prevalence and antimicrobial susceptibility data that can support evidence-based strategies to effectively tackle this animal and public health concern.

10.
Clin Spine Surg ; 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38446588

ABSTRACT

STUDY DESIGN: A prospective, randomized, placebo-controlled, double-blinded study. OBJECTIVE: To examine the effect of intraoperative epidural administration of Depo-Medrol on postoperative back pain and radiculitis symptoms in patients undergoing Transforaminal Lumbar Interbody Fusion (TLIF). SUMMARY OF BACKGROUND DATA: Postoperative pain is commonly experienced by patients undergoing spinal fusion surgery. Adequate management of intense pain is necessary to encourage early ambulation, increase patient satisfaction, and limit opioid consumption. Intraoperative steroid application has been shown to improve postoperative pain in patients undergoing lumbar decompression surgeries. There have been no studies examining the effect of epidural steroids on both back pain and radicular pain in patients undergoing TLIF. METHOD: In all, 151 patients underwent TLIF surgery using rh-BMP2 with 3 surgeons at a single institution. Of those, 116 remained in the study and were included in the final analysis. Based on a 1:1 randomization, a collagen sponge saturated with either Saline (1 cc) or Depo-Medrol (40 mg/1 cc) was placed at the annulotomy site on the TLIF level. Follow-up occurred on postoperative days 1, 2, 3, 7, and postoperative months 1, 2, and 3. Lumbar radiculopathy was measured by a modified symptom- and laterality-specific Visual Analog Scale (VAS) regarding the severity of back pain and common radiculopathy symptoms. RESULTS: The patients who received Depo-Medrol, compared with those who received saline, experienced significantly less back pain on postoperative days 1, 2, 3, and 7 (P<0.05). There was no significant difference in back pain beyond day 7. Radiculopathy-related symptoms such as leg pain, numbness, tingling, stiffness, and weakness tended to be reduced in the steroid group at most time points. CONCLUSION: This study provides Level 1 evidence that intraoperative application of Depo-Medrol during a TLIF surgery with rh-BMP2 significantly reduces back pain for the first week after TLIF surgery. The use of epidural Depo-Medrol may be a useful adjunct to multimodal analgesia for pain relief in the postoperative period.

11.
Neuropathology ; 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38414131

ABSTRACT

Herein, we report a case of a collision tumor involving a multinodular and vacuolating neuronal tumor (MVNT) and a diffuse astrocytoma. A collision tumor between these two entities has not previously been reported. The patient is a 35-year-old woman who presented with new-onset hearing loss and ringing in her right ear. Magnetic resonance imaging identified a non-enhancing mass involving the gray matter and subcortical white matter of the left middle frontal gyrus. Additionally, tiny clustered nodules were noted along the underlying subcortical ribbon and superficial subcortical white matter of the left superior frontal gyrus. The patient underwent a left frontal craniotomy and complete resection of the mass. Histologic examination of the resected specimen demonstrated a collision tumor consisting of a diffuse astrocytoma (isocitrate dehydrogenase [IDH] mutant, central nervous system [CNS] World Health Organization [WHO] grade 2) and an MVNT, with the latter demonstrating characteristic morphologic and immunohistochemical features.

12.
J Comp Pathol ; 208: 50-53, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38194723

ABSTRACT

A mild pneumocoelom was diagnosed by computed tomography in a stranded juvenile loggerhead sea turtle (Caretta caretta). After gas extraction by ultrasound-guided puncture, the animal did not improve and was subjected to hyperbaric oxygen therapy (HBOT). After HBOT, the turtle developed marked subcutaneous emphysema and was found dead the following morning. Gross lesions included a distended right atrium with numerous gas bubbles within the epicardium, gas bubbles in the hepatic, gastric and mesenteric veins, a small gas-filled bulla in the left lung and diffuse haemorrhages in the encephalon. Histological lesions included gas-like emboli in the lumen of the right atrium with myocardial necrosis, gas-like emboli in the lumina of intestinal, pulmonary and renal blood vessels and severe meningeal haemorrhages. From a forensic pathology perspective, the subcutaneous emphysema of immediate onset after HBOT and the greater severity of the histological lesions in blood vessels, heart, lung and brain differentiate this case from other cases of gas embolism in turtles due to incidental capture. Two factors contributed to this outcome: the existence of a probably unresolved pneumocoelom and the application of HBOT without an initial diagnosis that accurately indicated its use. Therefore, as in human medicine, the use of HBOT in sea turtles with lung lesions and pneumocoelom is discouraged. This is the first description of an iatrogenic gas embolism in a sea turtle.


Subject(s)
Embolism, Air , Subcutaneous Emphysema , Turtles , Humans , Animals , Embolism, Air/veterinary , Hemorrhage/veterinary , Subcutaneous Emphysema/veterinary , Iatrogenic Disease/veterinary
13.
Curr Opin Ophthalmol ; 35(3): 192-196, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38295156

ABSTRACT

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is a leading cause of visual impairment, and the increasing prevalence of diabetes and obesity will impact rates of visual impairment moving forward. Our review aims to synthesize the current body of evidence regarding the impact of lifestyle interventions, such as weight loss, bariatric surgery, and novel antidiabetic drugs, on DR. RECENT FINDINGS: Literature review revealed insufficient evidence regarding the impact of weight loss on DR. Preoperative DR patients undergoing bariatric surgery were found to have similar short-term chances of improvement or worsening DR. Progression of DR with glucagon-like peptide 1 receptor agonists treatments appears unrelated to specific drugs and was also observed with traditional antidiabetic medications. SUMMARY: Rapidly correcting HbA1c levels (≥2%) can paradoxically lead to early worsening DR. Patients considering weight loss, bariatric surgery, and novel antidiabetic drugs should be aware of the potential for DR progression, but they should not be discouraged, as achieving glycemic control is essential for reducing long-term morbidity and mortality from other diabetes-related complications. It is advisable to conduct a baseline retinal examination before treatment and continue monitoring during therapy. Further research is needed to understand the long-term effects of these treatments on DR.


Subject(s)
Bariatric Surgery , Diabetes Mellitus , Diabetic Retinopathy , Humans , Hypoglycemic Agents/therapeutic use , Diabetic Retinopathy/diagnosis , Bariatric Surgery/adverse effects , Weight Loss , Vision Disorders , Diabetes Mellitus/drug therapy
14.
Vet Pathol ; 61(1): 140-144, 2024 01.
Article in English | MEDLINE | ID: mdl-37377060

ABSTRACT

Citrobacter freundii, an opportunistic bacterial pathogen belonging to the family Enterobacteriaceae, has been sporadically reported in sea turtles. Here, the authors describe 3 unusual lesions associated with C. freundii infection in 3 loggerhead sea turtles stranded on the coast of Gran Canaria Island, Spain. It is possible that these 3 distinct lesions played a major role in the death of these turtles. The first turtle had caseous cholecystitis, a lesion not previously described in sea turtles. The second turtle had large intestinal diverticulitis, a rare condition in loggerheads. The third turtle had bilateral caseous salt gland adenitis. Histologically, numerous gram-negative bacilli were observed at the deepest edge of inflammation in all cases. Pure cultures of C. freundii were obtained from these 3 lesions. Molecular detection of C. freundii DNA in formalin-fixed paraffin-embedded samples from the lesions of the 3 turtles confirmed the microbiological isolation. These cases, in addition to expanding the limited body of knowledge on bacterial infections in sea turtles, highlight the potential pathogenic role of C. freundii in loggerhead turtles.


Subject(s)
Lymphadenitis , Turtles , Animals , Citrobacter freundii , Turtles/microbiology , Inflammation/veterinary , Lymphadenitis/veterinary , Spain
15.
Nanomaterials (Basel) ; 13(24)2023 Dec 14.
Article in English | MEDLINE | ID: mdl-38133033

ABSTRACT

Amorphous, glassy or disordered materials play important roles in developing structural materials from metals or ceramics, devices from semiconductors or medicines from organic compounds. Their local structure is frequently similar to crystalline ones. A computer program is presented here that runs under the Windows operating system on a PC to extract pair distribution function (PDF) from electron diffraction in a transmission electron microscope (TEM). A polynomial correction reduces small systematic deviations from the expected average Q-dependence of scattering. Neighbor distance and coordination number measurements are supplemented by either measurement or enforcement of number density. Quantification of similarity is supported by calculation of Pearson's correlation coefficient and fingerprinting. A rough estimate of fractions in a mixture is computed by multiple least-square fitting using the PDFs from components of the mixture. PDF is also simulated from crystalline structural models (in addition to measured ones) to be used in libraries for fingerprinting or fraction estimation. Crystalline structure models for simulations are obtained from CIF files or str files of ProcessDiffraction. Data from inorganic samples exemplify usage. In contrast to previous free ePDF programs, our stand-alone program does not need a special software environment, which is a novelty. The program is available from the author upon request.

16.
Braz Dent J ; 34(5): 1-21, 2023.
Article in English | MEDLINE | ID: mdl-38133464

ABSTRACT

BACKGROUND: The purpose of this article was to Evaluate the influence of sealer on the outcome of non-surgical endodontic treatment or retreatment of permanent teeth with apical periodontitis (PROSPERO registration: CRD42020205951). METHODOLOGY: A systematic review of original clinical studies was carried out following PRISMA guidelines to answer whether the type of sealer used in endodontic treatment or retreatment influences the repair of apical periodontitis determined by clinical and radiographic parameters. Electronic searches were performed in PubMed, Embase, Web of Science, Scopus, and the Cochrane Library database, until May 2023. Gray literature and a hand search of reference lists were also performed. The risk of bias was assessed using Cochrane RoB2 for randomized trials and the Newcastle-Ottawa Scale (NOS) for prospective and retrospective cohort and case-control studies. RESULTS: Among 1046 studies, a total of 819 were selected by title and abstract, resulting in 23 for full-text review. In total, 11 studies met the inclusion criteria (1467 patients/teeth with apical periodontitis). The quality assessment using RoB2 included five randomized control trials, of which four had medium risk and one had a low risk of bias. According to the NOS scale, five studies were classified as low risk and one study was considered as medium risk of bias. The sealer type and obturation techniques varied, and the mean follow-up time was 3.7 years. Most studies used two-dimensional radiographic criteria to assess the treatment outcome sealers and not cements. Eight studies did not find significant differences when comparing cements. The healing rates ranged from 56.7% to 90%. CONCLUSIONS: The results of this review support that the current endodontic sealers do not seem to influence the treatment outcome of permanent teeth with apical periodontitis. Although the studies had medium and low risk of bias, the results should be interpreted with caution. More randomized studies of long-term outcomes comparing filling materials are needed to strengthen this claim and allow for a meta-analysis.


Subject(s)
Periapical Periodontitis , Humans , Case-Control Studies , Periapical Periodontitis/therapy , Prospective Studies , Retrospective Studies , Treatment Outcome
17.
Support Care Cancer ; 32(1): 67, 2023 Dec 27.
Article in English | MEDLINE | ID: mdl-38150163

ABSTRACT

PURPOSE: The ADAURA trial demonstrated the superiority of osimertinib over a placebo with regard to disease-free survival, showing it to be indicated as an adjuvant therapy for treatment of non-small cell lung cancer with mutated epidermal growth factor receptor (EGFR). The aim of the present study was to conduct a cost-utility analysis and an analysis of the budgetary impact of adjuvant therapy with osimertinib in patients with non-small cell lung cancer with mutated EGFR who had undergone resection surgery with curative intent. METHODS: Analyses were based on the outcomes of the ADAURA clinical trial and were conducted through a Spanish National Health Service perspective. The outcome measures used were quality-adjusted life years (QALY). RESULTS: The average overall cost of adjuvant treatment with osimertinib over a period of 100 months in the overall sample of trial patients (stages IB-IIIA) was 220,961 €, compared with 197,849 € in the placebo group. Effectiveness, estimated according to QALY, was 6.26 years in the osimertinib group and 5.96 years in the placebo group, with the incremental cost-utility ratio being 77,040 €/QALY. With regard to the budgetary impact, it was estimated that, in 2021, approximately 1130 patients would be subsidiaries to receive osimertinib. This pertains to a difference of 17,375,330 € over 100 months to fund this treatment relative to no treatment. CONCLUSION: Taking into account a Spanish threshold of 24,000 €/QALY, the reduction in the acquisition cost of osimertinib will have to be greater than 10%, to obtain a cost-effective alternative.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Small Cell Lung Carcinoma , Humans , Cost-Benefit Analysis , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , State Medicine , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , ErbB Receptors/genetics
18.
Entropy (Basel) ; 25(11)2023 Oct 25.
Article in English | MEDLINE | ID: mdl-37998171

ABSTRACT

The black hole information puzzle can be resolved if two conditions are met. The first is that the information about what falls inside a black hole remains encoded in degrees of freedom that persist after the black hole completely evaporates. These degrees of freedom should be capable of purifying the information. The second is if these purifying degrees of freedom do not significantly contribute to the system's energy, as the macroscopic mass of the initial black hole has been radiated away as Hawking radiation to infinity. The presence of microscopic degrees of freedom at the Planck scale provides a natural mechanism for achieving these two conditions without running into the problem of the large pair-creation probabilities of standard remnant scenarios. In the context of Hawking radiation, the first condition implies that correlations between the in and out Hawking partner particles need to be transferred to correlations between the microscopic degrees of freedom and the out partners in the radiation. This transfer occurs dynamically when the in partners reach the singularity inside the black hole, entering the UV regime of quantum gravity where the interaction with the microscopic degrees of freedom becomes strong. The second condition suggests that the conventional notion of the vacuum's uniqueness in quantum field theory should fail when considering the full quantum gravity degrees of freedom. In this paper, we demonstrate both key aspects of this mechanism using a solvable toy model of a quantum black hole inspired by loop quantum gravity.

19.
BMC Res Notes ; 16(1): 334, 2023 Nov 14.
Article in English | MEDLINE | ID: mdl-37964369

ABSTRACT

OBJECTIVES: The hypermucoviscous-like phenotype has been described in Klebsiella pneumoniae species complex (KpSC) and was described as a contributor of increased virulence. This study described the characterization and whole-genome sequencing of an antibiotic susceptible and hypermucoviscous-like Klebsiella michiganensis 9273 clinical isolate. DATA DESCRIPTION: Here, we report the genome sequence of a K. michiganensis clinical isolate obtained from a urinary tract infection exhibiting the hypermucoviscous-like phenotype. The draft genome sequence consisted of 145 contigs and ~ 6.6 Mb genome size. The annotation revealed 6648 coding DNA sequences and 56 tRNA genes. The strain belongs to the sequence type (ST) 50, and the OXY-1 beta-lactam resistance gene, aph(3')-Ia gene for aminoglycoside resistance and multidrug efflux pumps were identified. The fyuA siderophore receptor of yersiniabactin siderophore was identified. Increased virulence was observed in Galleria mellonella larvae model and increased capsule production was determined by uronic acid quantification. The clinical implications of this phenotype are unknown, but the patient outcome might worsen compared to susceptible- or MDR-classical K. michiganensis isolates.


Subject(s)
Klebsiella Infections , Siderophores , Humans , Klebsiella pneumoniae , Anti-Bacterial Agents/pharmacology , beta-Lactamases/genetics
20.
Cureus ; 15(10): e46850, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37954775

ABSTRACT

We report on a case study involving a 58-year-old male with a pigmented corneal ulcer. The patient presented with a two-month history of an unresolved corneal ulcer in the oculus sinister (OS), accompanied by increasing ocular discomfort. His best corrected visual acuity (BCVA) was 20/20 oculus dexter and hand motion OS. Examination of OS revealed mild conjunctival injection, diffuse corneal edema, and the presence of a central pigmented lesion. Microbiological analysis via culture identified the causative agent as Ochroconis fungi, belonging to the dematiaceous species. Subsequently, the patient's condition was managed through a comprehensive regimen that included multiple topical antifungal agents, a topical antibiotic, and povidone-iodine drops. After two months of treatment, the patient exhibited improvement in his condition. His BCVA improved to counting fingers at a distance of two feet OS.

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