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1.
Radiol Med ; 2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39243293

RESUMO

PURPOSE: Artificial intelligence (AI) has revolutionized medical diagnosis and treatment. Breakthroughs in diagnostic applications make headlines, but AI in department administration (admin AI) likely deserves more attention. With the present study we conducted a systematic review of the literature on clinical impacts of admin AI in radiology. METHODS: Three electronic databases were searched for studies published in the last 5 years. Three independent reviewers evaluated the records using a tailored version of the Critical Appraisal Skills Program. RESULTS: Of the 1486 records retrieved, only six met the inclusion criteria for further analysis, signaling the scarcity of evidence for research into admin AI. CONCLUSIONS: Despite the scarcity of studies, current evidence supports our hypothesis that admin AI holds promise for administrative application in radiology departments. Admin AI can directly benefit patient care and treatment outcomes by improving healthcare access and optimizing clinical processes. Furthermore, admin AI can be applied in error-prone administrative processes, allowing medical professionals to spend more time on direct clinical care. The scientific community should broaden its attention to include admin AI, as more real-world data are needed to quantify its benefits. LIMITATIONS: This exploratory study lacks extensive quantitative data backing administrative AI. Further studies are warranted to quantify the impacts.

2.
Microb Pathog ; 196: 106932, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39303957

RESUMO

Pseudomonas aeruginosa demonstrates a remarkable capacity for adaptation and survival in diverse environments. Furthermore, its clinical importance is underscored by its intrinsic and acquired resistance to a wide range of antimicrobial agents, posing a substantial challenge in healthcare settings. Amidst this complex landscape of resistance, the Type VI Secretion System (T6SS) in P. aeruginosa adds yet another layer of intricacy and allows bacteria to engage in interbacterial competition, potentially influencing their resilience and pathogenicity. Whole genome sequencing (WGS) was conducted on the five isolates under investigation, enabling the identification of antibiotic resistance genes (ARGs) and mutations associated with resistance. All isolates exhibit class C and D ß-lactamases, displaying variant differences. The Resistance-nodulation-division (RND) antibiotic efflux pumps, crucial for multidrug resistance, have been encoded chromosomally. When exploring the role of the T6SS in urinary tract infections involving other bacteria, it was noted that P. aeruginosa isolates exhibited reduced counts when co-cultivated with other bacteria. The downregulation of the tssJ gene, associated with the T6SS under bacterial stress, and the exclusion of several cluster genes in this study suggest the hypothesis of a basal state rather than an attack/defence mechanism in the initial contact.

3.
Cureus ; 16(8): e66643, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39258079

RESUMO

Magnesium is an essential mineral with pivotal roles in various physiological processes, including enzyme function, neuromuscular regulation, and cardiovascular health. Magnesium's importance in critically ill pediatric patients is magnified due to its involvement in maintaining cellular homeostasis and potential therapeutic benefits. This review comprehensively analyzes magnesium's role in critical care pediatrics, focusing on its physiological mechanisms, clinical impact, and therapeutic strategies. Magnesium's functions in energy production, protein synthesis, and electrolyte balance underscore its significance in critical illness, where imbalances can lead to severe complications such as arrhythmias, neuromuscular disturbances, and respiratory issues. The review examines the clinical consequences of magnesium deficiency, including its impact on various body systems and the potential exacerbation of critical conditions. It also explores therapeutic strategies to optimize patient care, including supplementation practices, dosing considerations, and monitoring protocols. By summarizing recent research and clinical guidelines, this review aims to enhance understanding of magnesium's role in critical care and provide evidence-based recommendations for its management. The insights provided are intended to guide clinicians in integrating magnesium therapy into critical care practices, ultimately improving patient outcomes and advancing the management of critically ill pediatric patients.

4.
Cancers (Basel) ; 16(16)2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39199641

RESUMO

Glioblastoma: a highly aggressive brain tumor, presents substantial challenges in treatment and management, with surgical intervention playing a pivotal role in improving patient outcomes. Disparities in access to brain tumor surgery arise from a multitude of factors, including socioeconomic status, geographical location, and healthcare resource allocation. Low- and middle-income countries (LMICs) often face significant barriers to accessing surgical services, such as shortages of specialized neurosurgical expertise, limited healthcare infrastructure, and financial constraints. Consequently, glioblastoma patients in LMICs experience delays in diagnosis, suboptimal treatment, and poorer clinical outcomes compared to patients in high-income countries (HICs). The clinical impact of these disparities is profound. Patients in LMICs are more likely to be diagnosed at advanced disease stages, receive less effective treatment, and have lower survival rates than their counterparts in HICs. Additionally, disparities in access to surgical care exacerbate economic and societal burdens, emphasizing the urgent need for targeted interventions and health policy reforms to address healthcare inequities. This review highlights the importance of addressing global disparities in access to brain tumor surgery for glioblastoma through collaborative efforts, policy advocacy, and resource allocation, aiming to improve outcomes and promote equity in surgical care delivery for all glioblastoma patients worldwide.

5.
Genet Med ; 26(11): 101239, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-39140258

RESUMO

PURPOSE: To determine the frequency and clinical impact of loss-of-interruption (LOI) and duplication-of-interruption modifier variants of the HTT CAG and CCG repeat in a cohort of individuals with Huntington disease (HD). METHODS: We screened symptomatic HD participants from the UBC HD Biobank and 5 research sites for sequence variants. After variant identification, we examined the clinical impact and frequency in the reduced penetrance range. RESULTS: Participants with CAG-CCG LOI and CCG LOI variants have a similar magnitude of earlier onset of HD, by 12.5 years. The sequence variants exhibit ancestry-specific differences. Participants with the CAG-CCG LOI variant also have a faster progression of Total Motor Score by 1.9 units per year. Symptomatic participants with the CAG-CCG LOI variant show enrichment in the reduced penetrance range. The CAG-CCG LOI variant explains the onset of 2 symptomatic HD participants with diagnostic repeats below the pathogenetic range. CONCLUSION: Our findings have significant clinical implications for participants with the CAG-CCG LOI variant who receive inaccurate diagnoses near diagnostic cutoff ranges. Improved diagnostic testing approaches and clinical management are needed for these individuals. We present the largest and most diverse HTT CAG and CCG sequence variant cohort and emphasize their importance in clinical presentation in HD.

6.
Infect Drug Resist ; 17: 3579-3591, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39165848

RESUMO

Purpose: Infections cause high rates of illness and death in children worldwide. However, studies on the clinical value of metagenomic next-generation sequencing (mNGS) for immunocompromised children are still limited. Patients and Methods: From June 2021 to December 2023, 119 samples were collected at Pediatric Intensive Care Unit (PICU) of a single-center pediatric hospital and classified into two groups based on their immune states. We compared the diagnostic performance of mNGS and conventional microbiological test (CMT) for pathogen identification, and assessed the clinical impacts of mNGS. Results: Among the 119 samples, 48 (40.34%) belonged to the immunocompromised children. mNGS had a higher positivity rate than CMT (76.47% vs 55.46%, P = 0.0006). The positive percent agreement (PPA) of mNGS for immunocompromised children was higher compared to immunocompetent children (95.24% vs 77.78%). The most common pathogens for immunocompromised patients were gram-negative bacteria and herpesvirus. However, immunocompetent children showed a higher detection rate for gram-positive bacteria and respiratory viruses. Furthermore, the proportions of the positive impact of mNGS results were significantly higher in immunocompromised patients compared to immunocompetent patients for both diagnosis (91.67% vs 57.75%) and treatment (95.83% vs 64.79%) (P < 0.0001). Immunocompromised state, length of hospital stays, times stay in ICU, Pediatric Risk of Mortality (PRISM) score, neutrophil percentage (NEUT%) and the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) were considered independent factors for poor prognosis in critically ill pediatric patients. Conclusion: In patients from PICU, mNGS had a greater clinical significance in immunocompromised children compared to immunocompetent children. mNGS technology is an important auxiliary method for achieving accurate diagnosis and treatment of critically ill pediatric patients.

7.
Clin Transplant ; 38(6): e15375, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39031785

RESUMO

BACKGROUND: Cytomegalovirus infection (CMV) is a common complication after allogeneic hematopoietic stem cell transplantation (AHSCT). CMV infection increases transplantation costs; however, the extent of the financial burden may vary in different countries. This study aims to determine the clinical and economic impact of CMV infection in patients undergoing AHSCT in a middle-income country. METHODS: A total of 150 adult and pediatric patients post-AHSCT were included for analysis. In addition to incidence of CMV infections, data on graft versus host disease (GVHD) were also collected. Standard hospital charges for AHSCT and any additional transplantation-related expenditure within 12 months were also retrieved in 104 patients. RESULTS: CMV infection, acute GVHD and chronic GVHD occurred in 38.7%, 60.7%, and 22.0% of patients, respectively. Patients with CMV infections had higher readmission rates compared to those who did not (67.2% vs. 47.8%; p = 0.020). Additional expenditure was seen in HLA-haploidentical AHSCT and CMV infection (MYR11 712.25/USD2 504.49; p < 0.0001 and MYR5 807.24/USD1 241.79; p = 0.036), respectively. CONCLUSION: This single-center study demonstrated that patients who underwent HLA-haploidentical AHSCT and subsequently developed CMV infection had higher transplantation expenditures compared to those who had matched-related transplantation. Further studies should be conducted to evaluate if primary prophylaxis against CMV is cost-effective, especially in patients who undergo HLA-haploidentical AHSCT.


Assuntos
Infecções por Citomegalovirus , Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante Homólogo , Humanos , Infecções por Citomegalovirus/economia , Infecções por Citomegalovirus/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/economia , Masculino , Feminino , Adulto , Seguimentos , Citomegalovirus/isolamento & purificação , Criança , Doença Enxerto-Hospedeiro/economia , Doença Enxerto-Hospedeiro/etiologia , Adolescente , Pessoa de Meia-Idade , Adulto Jovem , Prognóstico , Fatores de Risco , Pré-Escolar , Estudos Retrospectivos , Incidência , Condicionamento Pré-Transplante/efeitos adversos
8.
J Infect Dis ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008608

RESUMO

BACKGROUND: Clinical impact of plasma metagenomic next-generation sequencing (mNGS) on infection diagnosis and antimicrobial therapy in immunocompromised patients with suspected infection remains unclear. METHODS: Between March and December 2022, 424 cases with fever, infection history, mechanical ventilation, or imaging abnormalities underwent plasma mNGS testing at a single center. Eleven patients have received solid organ transplantation, and the remaining patients were categorised into febrile neutropenia (FN), non-neutropenia (NN), and non-haematologic disease (NTHD) groups based on immunosuppression severity. The diagnostic rate of infection and the utilisation of antimicrobial agents based on mNGS were assessed. RESULTS: The use of mNGS significantly improved the diagnostic rates for fungi in the FN (56.1%, P = 0.003) and NN (58.8%, P = 0.008) groups versus the NHD group (33.3%). Positive impacts associated with therapy were significantly greater than negative impacts across all three groups (all P < 0.001), and the utilisation of escalation therapy was significantly more frequent in the FN group than in the NN groups (P = 0.006). Over 70% of cases with negative mNGS results across the three groups underwent de-escalation therapy, with >1/3 being discontinued, preventing antimicrobial overuse. CONCLUSIONS: Plasma mNGS has a clinically confirmed positive impact in immunocompromised patients with neutropenia, improving the diagnosis of fungal infections and antimicrobial therapy.

9.
Transpl Int ; 37: 12469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952482

RESUMO

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.


Assuntos
Farmacorresistência Bacteriana Múltipla , Transplante de Órgãos , Humanos , Transplante de Órgãos/efeitos adversos , Transplantados , Antibacterianos/uso terapêutico , Prevalência , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/epidemiologia , Países em Desenvolvimento
10.
Curr Pharm Teach Learn ; 16(8): 102117, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38824814

RESUMO

INTRODUCTION: Cardiovascular disease (CVD) is currently the leading cause of mortality and morbidity worldwide. A competent healthcare workforce working in primary care delivering disease management services efficiently is the cornerstone of well performing health systems, impacting patient outcomes positively. The aim of this study was to evaluate the effectiveness of a training course to support pharmacists working in General Practitioner (GP) practices; and to evaluate its impact on practice. METHODS: A before and after evaluation model was employed to assess the effectiveness of training resorting to a survey exploring self-confidence and knowledge on clinical management of three CVD topics: Atrial Fibrillation (AF), Hypertension and hyperlipidaemia. Before and after training data (immediate and retained after 6 months) were analysed at the Primary Care Network (PCN) and GP Practice level of the pharmacists who took part in the training sessions. Data were analysed in IBM SPSS v.29 resorting to paired samples t-test and Cohen's d for estimation of the effect size. Independent samples t-tests were performed for a sample group of PCNs and GP practices with and without training (comparator group). RESULTS: An improvement with large effect size was observed in pharmacists' self-confidence and knowledge related to the hypertension topic, suggesting potential practical benefit. For the topics of AF and hyperlipidaemia, pharmacists' confidence also increased with a large effect size, but for knowledge, the effect size of the increase was medium or small. Data suggests that pharmacists' practice has improved in both groups after 6 months, which suggests that it was not a sole result of the training. CONCLUSIONS: This study provide evidence that the course improved pharmacists' knowledge and self-confidence, likely to contribute to performance in their clinical practice. Patients' clinical benefit is expected from pharmacists' improved capacity to effectively engage in medicines optimisation.


Assuntos
Doenças Cardiovasculares , Farmacêuticos , Atenção Primária à Saúde , Humanos , Atenção Primária à Saúde/estatística & dados numéricos , Farmacêuticos/psicologia , Farmacêuticos/estatística & dados numéricos , Doenças Cardiovasculares/terapia , Masculino , Feminino , Inquéritos e Questionários , Adulto , Empoderamento , Pessoa de Meia-Idade , Gerenciamento Clínico
11.
Eur Heart J Cardiovasc Imaging ; 25(10): 1441-1450, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38860493

RESUMO

AIMS: Transthoracic echocardiography is recommended in all patients with acute coronary syndrome but is time-consuming and lacks an evidence base. We aimed to assess the feasibility, diagnostic accuracy, and time efficiency of hand-held echocardiography in patients with acute coronary syndrome and describe the impact of echocardiography on clinical management in this setting. METHODS AND RESULTS: Patients with acute coronary syndrome underwent both hand-held and transthoracic echocardiographies with agreement between key imaging parameters assessed using kappa statistics. The immediate clinical impact of hand-held echocardiography in this population was systematically evaluated. Overall, 262 patients (65 ± 12 years, 71% male) participated. Agreement between hand-held and transthoracic echocardiographies was good-to-excellent (kappa 0.60-1.00) with hand-held echocardiography having an overall negative predictive value of 95%. Hand-held echocardiography was performed rapidly (7.7 ± 1.6 min) and completed a median of 5 (interquartile range 3-20) h earlier than transthoracic echocardiography. Systematic hand-held echocardiography in all patients with acute coronary syndrome identified an important cardiac abnormality in 50%, and the clinical management plan was changed by echocardiography in 42%. In 85% of cases, hand-held echocardiography was sufficient for patient decision-making, and transthoracic echocardiography was no longer deemed necessary. CONCLUSION: In patients with acute coronary syndrome, hand-held echocardiography provides comparable results to transthoracic echocardiography, can be more rapidly applied, and gives sufficient imaging information for decision-making in the vast majority of patients. Systematic echocardiography has clinical impact in half of patients, supporting the clinical utility of echocardiography in this population and providing an evidence base for current guidelines.


Assuntos
Síndrome Coronariana Aguda , Ecocardiografia , Humanos , Síndrome Coronariana Aguda/diagnóstico por imagem , Masculino , Feminino , Ecocardiografia/métodos , Idoso , Pessoa de Meia-Idade , Estudos de Viabilidade , Hospitalização , Estudos de Coortes
12.
Front Neurol ; 15: 1394476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779218

RESUMO

Background: This study aimed to develop a nomogram for predicting temporary acute agitated delirium after surgery in patients with chronic subdural hematoma (CSH) without neurological compromise and hospitalized in the neurosurgery. Methods: We included 289 patients with chronic subdural hematoma (CSH) from the medical information system of Yuebei People's Hospital of Shaoguan City, Guangdong Province, and collected 16 clinical indicators within 24 h of admission. We used the least absolute shrinkage and selection operator (LASSO) regression to identify risk factors. We established a multivariate logistic regression model and constructed a nomogram. We performed internal validation by 1,000 bootstrap samples; we plotted a receiver operating curve (ROC) and calculated the area under the curve (AUC), sensitivity, and specificity. We also evaluated the calibration of our model by the calibration curve and the Hosmer-Lemeshow goodness-of-fit test (HL test). We performed a decision curve analysis (DCA) and a clinical impact curve (CIC) to assess the net clinical benefit of our model. Results: The nomogram included alcoholism history, hepatic insufficiency, verbal rating scale for postoperative pain (VRS), pre-hospital modified Rankin Scale (mRS), and preoperative hematoma thickness as predictors. Our model showed satisfactory diagnostic performance with an AUC value of 0.8474 in the validation set. The calibration curve and the HL test showed good agreement between predicted and observed outcomes (p = 0.9288). The DCA and CIC showed that our model had a high predictive ability for the occurrence of postoperative delirium in patients with CSDH. Conclusion: We identified alcoholism, liver dysfunction, pre-hospital mRS, preoperative hematoma thickness, and postoperative VRS pain as predictors of postoperative delirium in chronic subdural hematoma patients. We developed and validated a multivariate logistic regression model and a nomogram.

14.
Alzheimers Dement (N Y) ; 10(1): e12451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505833

RESUMO

INTRODUCTION: Biomarker-informed criteria were proposed for the diagnosis of Alzheimer's disease (AD) by the National Institute on Aging and the Alzheimer's Association (NIA-AA) in 2011; however, the adequacy of this criteria has not been sufficiently evaluated. METHODS: ReDeMa (Red de Demencias de Madrid) is a regional cohort of patients attending memory and neurology clinics. Core cerebrospinal fluid biomarkers were obtained, NIA-AA diagnostic criteria were considered, and changes in diagnosis and management were evaluated. RESULTS: A total of 233 patients were analyzed (mean age 70 years, 50% women, 73% AD). The diagnostic language was modified significantly, with a majority assumption of NIA-AA definitions (69%). Confidence in diagnosis increased from 70% to 92% (p < 0.0005) and management was changed in 71% of patient/caregivers. The influence of neurologist's age or expertise on study results was minimal. DISCUSSION: The NIA-AA criteria are adequate and utile for usual practice in memory and neurology clinics, improving diagnostic confidence and significantly modifying patient management. HIGHLIGHTS: Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers increase diagnostic certainty regardless of the neurologist.AD CSF biomarkers lead to changes in disease management .Biomarker-enriched, 2011 NIA-AA diagnostic criteria are adequate for usual practice.

15.
Clin Chem Lab Med ; 62(6): 1158-1166, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38353154

RESUMO

OBJECTIVES: To accurately evaluate non-ST-elevated acute cardiac syndrome (NSTE-ACS), the quality of high-sensitive cardiac troponin (hs-cTn) assays is of vital importance. The 2020 revision of the NSTE-ACS guideline includes clinical decision-limits (CDL's) to both rule-in and rule-out NSTE-ACS for most commercially available platforms, providing both 0/1 h and 0/2 h delta limits. Our study evaluated whether laboratories are able to meet the analytical performance specifications for imprecision (APS) for hs-cTnT. METHODS: Results from external quality assurance (EQA) in commutable samples were used to evaluate the current and historic performance of analyzers. The performance of analyzers that either passed or failed to comply with 0/1 h-APS were used on a real-world dataset of first hs-cTnT-values to simulate 10.000 samples of t=0, t=1 and t=2 h values with multiple delta's for all relevant CDL's. We compared the simulated values to the input values to obtain the percentage of aberrant results simulated. RESULTS: The majority of analyzers complies with APS for rule-in in 2022 (0/1 h: 90.4 % and 0/2 h: 100 %), compliance for the 0/1 h rule-out is still far from optimal (0/1 h: 30.7 %, 0/2 h: 75.4 %), with improving compliance over the past years (rule-in p=<0.0001, rule-out p=0.011, χ2). Whilst 0/1 h-APS-passing analyzers have a minute risk to falsely rule-out patients whom should be ruled-in (0.0001 %), failing performance increases this risk to 2.1 % upon using 0/1 h CDL's. Here, adopting 0/2 h CDL's is favorable (0.01 %). CONCLUSIONS: Laboratories that fail to meet hs-cTnT 0/1 h-APS should improve their performance to the required and achievable level. Until performance is reached clinics should adopt the 0/2 h CDL's.


Assuntos
Troponina T , Humanos , Troponina T/sangue , Troponina T/análise , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/sangue , Controle de Qualidade , Garantia da Qualidade dos Cuidados de Saúde , Guias de Prática Clínica como Assunto
16.
EJHaem ; 5(1): 93-104, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38406551

RESUMO

Flow cytometry-based immunophenotyping is a mainstay of diagnostics in acute myeloid leukaemia (AML). Aberrant CD56 and T-cell antigen expression is observed in a fraction subset of AML cases, but the clinical relevance remains incompletely understood. Here, we retrospectively investigated the association of CD56 and T-cell marker expression with disease-specific characteristics and outcome of 324 AML patients who received intensive induction therapy at our centre between 2011 and 2019. We found that CD2 expression was associated with abnormal non-complex karyotype, NPM1 wild-type status and TP53 mutation. CD2 also correlated with a lower complete remission (CR) rate (47.8% vs. 71.6%, p = 0.03). CyTdT and CD2 were associated with inferior 3-year event-free-survival (EFS) (5.3% vs. 33.5%, p = 0.003 and 17.4% vs. 33.1%, p = 0.02, respectively). CyTdT expression was also correlated with inferior relapse-free survival (27.3% vs. 48.8%, p = 0.04). In multivariable analyses CD2 positivity was an independent adverse factor for EFS (HR 1.72, p = 0.03). These results indicate a biological relevance of aberrant T-cell marker expression in AML and provide a rationale to further characterise the molecular origin in T-lineage-associated AML.

17.
J Pharm Sci ; 113(5): 1401-1414, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38220088

RESUMO

Silicone oil is a commonly used lubricant in pre-filled syringes (PFSs) and can migrate over time into solution in the form of silicone oil particles (SiOPs). The presence of these SiOPs can result in elevated subvisible particle counts in PFS drug products compared to other drug presentations such as vials or cartridges. Their presence in products presents analytical challenges as they complicate quantitation and characterization of other types of subvisible particles in solution. Previous studies have suggested that they can potentially act as adjuvant resulting in potential safety risks for patients. In this paper we present several analytical case studies describing the impact of the presence of SiOPs in biotherapeutics on the analysis of the drug as well as clinical case studies examining the effect of SiOPs on patient safety. The analytical case studies demonstrate that orthogonal techniques, especially flow imaging, can help differentiate SiOPs from other types of particulate matter. The clinical case studies showed no difference in the observed patient safety profile across multiple drugs, patient populations, and routes of administration, indicating that the presence of SiOPs does not impact patient safety.


Assuntos
Produtos Biológicos , Óleos de Silicone , Humanos , Óleos de Silicone/análise , Tamanho da Partícula , Preparações Farmacêuticas , Material Particulado , Seringas
18.
J Neurol ; 271(2): 733-747, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37891417

RESUMO

The role of genetic testing in neurologic clinical practice has increased dramatically in recent years, driven by research on genetic causes of neurologic disease and increased availability of genetic sequencing technology. Genetic testing is now indicated for adults with a wide range of common neurologic conditions. The potential clinical impacts of a genetic diagnosis are also rapidly expanding, with a growing list of gene-specific treatments and clinical trials, in addition to important implications for prognosis, surveillance, family planning, and diagnostic closure. The goals of this review are to provide practical guidance for clinicians about the role of genetics in their practice and to provide the neuroscience research community with a broad survey of current progress in this field. We aim to answer three questions for the neurologist in practice: Which of my patients need genetic testing? What testing should I order? And how will genetic testing help my patient? We focus on common neurologic disorders and presentations to the neurology clinic. For each condition, we review the most current guidelines and evidence regarding indications for genetic testing, expected diagnostic yield, and recommended testing approach. We also focus on clinical impacts of genetic diagnoses, highlighting a number of gene-specific therapies recently approved for clinical use, and a rapidly expanding landscape of gene-specific clinical trials, many using novel nucleotide-based therapeutic modalities like antisense oligonucleotides and gene transfer. We anticipate that more widespread use of genetic testing will help advance therapeutic development and improve the care, and outcomes, of patients with neurologic conditions.


Assuntos
Doenças do Sistema Nervoso , Neurociências , Adulto , Humanos , Doenças do Sistema Nervoso/diagnóstico , Doenças do Sistema Nervoso/genética , Doenças do Sistema Nervoso/terapia , Testes Genéticos , Neurologistas , Instituições de Assistência Ambulatorial
19.
Clin Infect Dis ; 78(2): 248-258, 2024 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-37738153

RESUMO

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Humanos , Acinetobacter baumannii/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Estudos Prospectivos , Testes de Sensibilidade Microbiana , Infecções por Acinetobacter/tratamento farmacológico , Infecções por Acinetobacter/epidemiologia , Infecções por Acinetobacter/microbiologia , beta-Lactamases/genética , Proteínas de Bactérias/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico
20.
Pancreatology ; 24(1): 137-145, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38016862

RESUMO

BACKGROUND: /Objectives: This study aimed to evaluate the frequency, clinical impact, and risk factors of post-pancreatectomy acute pancreatitis (PPAP) after pancreatoduodenectomy (PD) according to the definition proposed by the International Study Group for Pancreatic Surgery (ISGPS). METHODS: patients undergoing PD between 2010 and 2021 were retrospectively analyzed. PPAP was defined according to the ISGPS criteria, including elevated serum amylase for 48 h and concurring pancreatitis alterations on a CT scan. RESULTS: 272 patients were finally included in the study. PPAP occurred in 40 (14.7 %) patients, and it was significantly related to higher rates of clinically-relevant postoperative pancreatic fistula (CR-POPF) (p < 0.001), post-pancreatectomy hemorrhage (PPH) (p < 0.001) and major complications (Clavien-Dindo ≥ 3a) (p < 0.001). Moreover, PPAP in the absence of CR-POPF (n = 18) was significantly related to longer hospital stay (p < 0.001), PPH (p < 0.001), major complications (Clavien-Dindo≥ 3a, p = 0.001) and higher intensive care unit costs (p = 0.029) compared to patients not developing PPAP. In the univariable and multivariable analysis, the duct size (p = 0.004) and high-risk pathologies (p = 0.004) but not intraoperative bleeding (p = 0.066) represented independent risk factors for PPAP. In the same analysis, patients receiving a bridging therapy with low molecular-weight heparin showed significantly lower rates of PPAP (p = 0.045). CONCLUSIONS: PPAP represents a relevant complication after PD. Its risk factors are similar to those for CR-POPF, while anticoagulants could represent a possible prevention strategy.


Assuntos
Pancreatectomia , Pancreatite , Propilaminas , Humanos , Pancreatectomia/efeitos adversos , Pancreaticoduodenectomia/efeitos adversos , Estudos Retrospectivos , Pancreatite/etiologia , Pancreatite/complicações , Doença Aguda , Fatores de Risco , Fístula Pancreática/etiologia , Fístula Pancreática/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
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