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3.
Front Neurol ; 15: 1395413, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711561

RESUMO

Background: Diagnosing Dementia with Lewy Bodies (DLB) remains a challenge in clinical practice. The use of 123I-ioflupane (DaTscan™) SPECT imaging, which detects reduced dopamine transporter (DAT) uptake-a key biomarker in DLB diagnosis-could improve diagnostic accuracy. However, DAT imaging is underutilized despite its potential, contributing to delays and suboptimal patient management. Methods: This review evaluates DLB diagnostic practices and challenges faced within the U.S. by synthesizing information from current literature, consensus guidelines, expert opinions, and recent updates on DaTscan FDA filings. It contrasts DAT SPECT with alternative biomarkers, provides recommendations for when DAT SPECT imaging may be indicated and discusses the potential of emerging biomarkers in enhancing diagnostic approaches. Results: The radiopharmaceutical 123I-ioflupane for SPECT imaging was initially approved in Europe (2000) and later in the US (2011) for Parkinsonism/Essential Tremor. Its application was extended in 2022 to include the diagnosis of DLB. DaTscan's diagnostic efficacy for DLB, with its sensitivity, specificity, and predictive values, confirms its clinical utility. However, US implementation faces challenges such as insurance barriers, costs, access issues, and regional availability disparities. Conclusion: 123I-ioflupane SPECT Imaging is indicated for DLB diagnosis and differential diagnosis of Alzheimer's Disease, particularly in uncertain cases. Addressing diagnostic obstacles and enhancing physician-patient education could improve and expedite DLB diagnosis. Collaborative efforts among neurologists, geriatric psychiatrists, psychologists, and memory clinic staff are key to increasing diagnostic accuracy and care in DLB management.

5.
J Am Pharm Assoc (2003) ; : 102124, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38759794

RESUMO

BACKGROUND: People with diabetes who inject insulin with pen devices may reuse the pen needles (PNs), a practice that can cause PN tip deformity, breakage, and contamination, and that is associated with lipohypertrophy and injection-related pain. OBJECTIVE: This retrospective study aimed to estimate the extent of PN reuse among people with diabetes in two insured populations in the United States. METHODS: Using claims data for Commercial Fully Insured (CFI) and Medicare Advantage (MA) populations from 1-Oct-2018 to 31-Dec-2022, we identified adults with type 1 or type 2 diabetes (T1D/T2D) who had ≥1 claim for PNs and ≥2 claims for insulin from 1-Jan-2019 to 31-Dec-2021, with continuous medical/pharmacy eligibility for 3 months before first claim and 1 year after (follow-up). Those receiving hospice or palliative care or using mail-order prescriptions were excluded. We compared actual annual fill rate of PNs with expected fill rate (assuming single use) according to prescribed insulin regimen. Whether the annual actual-to-expected ratio for PN numbers equaled 1 was evaluated using sign tests with 2-sided p-values. RESULTS: Median annual actual-to-expected ratios ranged from 0.41 (T1D basal+prandial cohort) to 0.82 (T2D basal cohort; all p<0.001) in the CFI population (N=10,854), and from 0.55 (TID basal+prandial) to 1.10 (T2D basal and basal+prandial; p=0.382 to <0.001) in the MA population (N=32,495); medians were 0.34 and 0.55 for four expected T2D basal+prandial injections/day in CFI and MA populations, respectively (p<0.001). Annual actual-to-expected ratios were <1 for 62% and 47% of CFI and MA populations, respectively. An estimated 2-27% and 0-17%, respectively, depending on insulin regimen, had inadequate supplies of PNs suggesting that PNs could have been used ≥5 times. CONCLUSIONS: These findings highlight the need for educating people with diabetes about reasons for avoiding PN reuse and the key role that pharmacists can play in providing this information and adequate supplies of PNs.

6.
J Pharm Pract ; : 8971900241256725, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38807033

RESUMO

Objective: This review aims to emphasize the role of pharmacists for optimization of evidence-based outcomes of finerenone in multidisciplinary kidney care teams during the early detection process of CKD patients. Data Sources: A PubMed literature search was performed using keywords pharmacists, chronic kidney disease (CKD), type 2 diabetes (T2D), and finerenone. Study Selection and Data Extraction: All English-language studies on the role of pharmacists in managing CKD patients or finerenone prescriptions were evaluated. Data Synthesis: CKD is a major health problem affecting millions worldwide, especially those with T2D. In recent years, new drugs have been added to the treatment options for patients with T2D and CKD, which have been shown to reduce the risk of cardiovascular and renal complications in large clinical trials. Conclusions: Pharmacists can help detect and treat CKD in patients with T2D. They may use indicators to identify potential candidates for appropriate finerenone therapy, such as stage of CKD, albuminuria level, serum potassium concentration, and use of RAAS inhibitors. Pharmacists can provide education on the benefits and usage of finerenone, monitor response to therapy, adjust the medications and doses, prevent drug interactions, help with adherence and tolerability issues, and coordinate with other healthcare providers.

7.
Infect Control Hosp Epidemiol ; : 1-7, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38818881

RESUMO

OBJECTIVE: To evaluate the clinical impact and features associated with repeat tracheal aspirate (TA) cultures in children admitted to the intensive care unit. DESIGN: Retrospective cohort study. SETTING: A 338-bed freestanding, tertiary pediatric academic medical center with pediatric medical intensive care unit (PICU) and cardiac intensive care units (CICU). PATIENTS: Children ≤18 years of age who were admitted to either the PICU or CICU who had ≥2 TA cultures in a single intensive care admission. METHODS: Patients with ≥2 TA cultures between 2018 and 2019 were included in this study. The following information was collected: patient demographics, clinical data summarizing patient condition at the time of culture collection, number of TA cultures per patient, antibiotic usage, and microbiologic data. Descriptive statistics established the frequency of TA collection, time between culturing, clinical reasoning for collection, antibiotic exposure, and development of multidrug-resistant organisms (MDRO). RESULTS: Sixty-three patients had repeat TA cultures and accounted for 252 TA cultures during the study period. Most patients with repeat TA cultures were admitted to the PICU (71%) and were male (65%). A median of 3 TA cultures per patient were obtained with 50% of repeat cultures occurring within 7 days from the previous culture. Sixty-six percent of patients had the same organism cultured on ≥2 TA cultures. Most antibiotics were not modified or continued to treat the results of the TA culture. CONCLUSIONS: Repeat TA cultures frequently show the same pathogens, and results do not often influence antibiotic selection or usage. Repeat TA cultures did demonstrate the development of MDROs.

8.
MedEdPORTAL ; 20: 11391, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654890

RESUMO

Introduction: Many people experience trauma, and its cumulative effects throughout the life span can alter health, development, and well-being. Despite this, few publications focusing on interpersonal trauma include a holistic understanding of the nature and widespread exposure of trauma experiences for patients. We developed an educational resource to teach residents about identifying and intervening with patients who experience trauma across the life span using a trauma-informed care (TIC) perspective. Methods: We created a 4-hour educational session for residents that included didactics, a virtual visit with a domestic violence shelter, a discussion with a person who had experienced trauma, and role-playing. A pretest/posttest retrospective survey assessed resident confidence level in identifying and intervening with patients who may have experienced trauma. We used the Wilcoxon signed rank test to compare pretest and posttest scores and the Kruskal-Wallis test to compare responses by residency type and year. Free-text questions were analyzed for thematic content. Results: During the 2021-2022 academic year, 72 of 90 residents (80%) from four residency programs attended and evaluated the session. More than 90% of respondents reported the session met their educational needs and provided them with new ideas, information, and practical suggestions to use in their clinical endeavors. The results demonstrated significantly increased confidence on most of the metrics measured. Discussion: This session significantly improved residents' confidence in identifying and intervening with patients who have had trauma experiences using a TIC perspective, which may lead them to provide improved patient care to those who have experienced trauma.


Assuntos
Internato e Residência , Humanos , Internato e Residência/métodos , Inquéritos e Questionários , Estudos Retrospectivos , Médicos/psicologia , Educação de Pós-Graduação em Medicina/métodos , Feminino
9.
Ann Plast Surg ; 92(4S Suppl 2): S234-S240, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38556680

RESUMO

BACKGROUND: Simultaneous free flap breast reconstruction combined with contralateral mastopexy or breast reduction can increase patient satisfaction and minimize the need for a second procedure. Surgeon concerns of increases in operative time, postoperative complications, and final breast symmetry may decrease the likelihood of these procedures being done concurrently. This study analyzed postoperative outcomes of simultaneous contralateral mastopexy or breast reduction with free flap breast reconstruction. METHODS: By using the American College of Surgeons National Surgical Quality Improvement Program database (2010-2020), we analyzed 2 patient cohorts undergoing (A) free flap breast reconstruction only and (B) free flap breast reconstruction combined with contralateral mastopexy or breast reduction. The preoperative variables assessed included demographic data, comorbidities, and perioperative data. Using a neighbor matching algorithm, we performed a 1:1 propensity score matching of 602 free flap breast reconstruction patients and 621 with concurrent contralateral operation patients. Bivariate analysis for postoperative surgical and medical complications was performed for outcomes in the propensity-matched cohort. RESULTS: We identified 11,308 cases who underwent microsurgical free flap breast reconstruction from the American College of Surgeons National Surgical Quality Improvement Program database from the beginning of 2010 to the end of 2020. A total of 621 patients underwent a free flap breast reconstruction combined with contralateral mastopexy or breast reduction. After propensity score matching, there were no significant differences in patient characteristics, perioperative variables or postoperative medical complications between the 2 cohorts. CONCLUSIONS: Simultaneous free flap breast reconstruction combined with contralateral mastopexy or breast reduction can be performed safely and effectively without an increase in postoperative complication rates. This can improve surgeon competence in offering this combination of procedures as an option to breast cancer survivors, leading to better patient outcomes in terms of symmetrical and aesthetically pleasing results, reduced costs, and elimination of the need for a second operation.


Assuntos
Neoplasias da Mama , Retalhos de Tecido Biológico , Mamoplastia , Humanos , Feminino , Melhoria de Qualidade , Estudos Retrospectivos , Mamoplastia/métodos , Mastectomia/efeitos adversos , Neoplasias da Mama/cirurgia , Neoplasias da Mama/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia
10.
Am J Public Health ; 114(S5): S402-S404, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38547464

RESUMO

We explored the role of school nurses during the COVID-19 pandemic by conducting interviews and focus groups with them in 2022 and 2023 in an urban public school district. Findings indicated that school nurses played an essential public health role in engaging the school community, overseeing COVID-19 testing, and enforcing risk mitigation strategies during the pandemic. Our results contribute to understanding school nurses' experiences during the pandemic and highlight the need for training and support for their vital role. (Am J Public Health. 2024;114(S5):S402-S404. https://doi.org/10.2105/AJPH.2024.307591).


Assuntos
COVID-19 , Papel do Profissional de Enfermagem , Serviços de Enfermagem Escolar , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Serviços de Enfermagem Escolar/organização & administração , Grupos Focais , SARS-CoV-2 , Instituições Acadêmicas/organização & administração , Feminino , Masculino
11.
bioRxiv ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38405939

RESUMO

Parkinson's disease (PD) is associated with autoimmune T cells that recognize the protein alpha-synuclein in a subset of individuals. Multiple neuroantigens are targets of autoinflammatory T cells in classical central nervous system autoimmune diseases such as multiple sclerosis (MS). Here, we explored whether additional autoantigenic targets of T cells in PD. We generated 15-mer peptide pools spanning several PD-related proteins implicated in PD pathology, including GBA, SOD1, PINK1, parkin, OGDH, and LRRK2. Cytokine production (IFNγ, IL-5, IL-10) against these proteins was measured using a fluorospot assay and PBMCs from patients with PD and age-matched healthy controls. This approach identified unique epitopes and their HLA restriction from the mitochondrial-associated protein PINK1, a regulator of mitochondrial stability, as an autoantigen targeted by T cells. The T cell reactivity was predominantly found in male patients with PD, which may contribute to the heterogeneity of PD. Identifying and characterizing PINK1 and other autoinflammatory targets may lead to antigen-specific diagnostics, progression markers, and/or novel therapeutic strategies for PD.

12.
JAMA Netw Open ; 7(2): e2355707, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38349656

RESUMO

Importance: There are an increasing number of medications with a high level of evidence for pharmacogenetic-guided dosing (PGx drugs). Knowledge of the prevalence of dispensings of PGx drugs and their associated genes may allow hospitals and clinical laboratories to determine which pharmacogenetic tests to implement. Objectives: To investigate the prevalence of outpatient dispensings of PGx drugs among Medicaid-insured youths, determine genes most frequently associated with PGx drug dispenses, and describe characteristics of youths who were dispensed at least 1 PGx drug. Design, Setting, and Participants: This serial cross-sectional study includes data from 2011 to 2019 among youths aged 0 to 17 years in the Marketscan Medicaid database. Data were analyzed from August to December 2022. Main Outcomes and Measures: PGx drugs were defined as any medication with level A evidence as determined by the Clinical Pharmacogenetics Implementation Consortium (CPIC). The number of unique youths dispensed each PGx drug in each year was determined. PGx drugs were grouped by their associated genes for which there was CPIC level A evidence to guide dosing, and a dispensing rate (No. of PGx drugs/100 000 youths) was determined for each group for the year 2019. Demographics were compared between youths dispensed at least 1 PGx drug and those not dispensed any PGx drugs. Results: The number of Medicaid-insured youths queried ranged by year from 2 078 683 youths in 2011 to 4 641 494 youths in 2017, including 4 126 349 youths (median [IQR] age, 9 [5-13] years; 2 129 926 males [51.6%]) in 2019. The proportion of Medicaid-insured youths dispensed PGx drugs increased from 289 709 youths (13.9%; 95% CI, 13.8%-14.0%) in 2011 to 740 072 youths (17.9%; 95% CI, 17.9%-18.0%) in 2019. Genes associated with the most frequently dispensed medications were CYP2C9, CYP2D6, and CYP2C19 (9197.0 drugs [95% CI, 9167.7-9226.3 drugs], 8731.5 drugs [95% CI, 8702.5-8759.5 drugs], and 3426.8 drugs [95% CI, 3408.1-3443.9 drugs] per 100 000 youths, respectively). There was a higher percentage of youths with at least 1 chronic medical condition among youths dispensed at least 1 PGx drug (510 445 youths [69.0%; 95% CI, 68.8%-69.1%]) than among 3 386 277 youths dispensed no PGx drug (1 381 544 youths [40.8%; 95% CI, 40.7%-40.9%) (P < .001) in 2019. Conclusions and Relevance: In this study, there was an increasing prevalence of dispensings for PGx drugs. This finding suggests that pharmacogenetic testing of specific drug-gene pairs should be considered for frequently prescribed PGx drugs and their implicated genes.


Assuntos
Medicaid , Testes Farmacogenômicos , Masculino , Estados Unidos , Humanos , Adolescente , Pré-Escolar , Criança , Estudos Transversais , Citocromo P-450 CYP2D6 , Bases de Dados Factuais
13.
J Parkinsons Dis ; 14(1): 135-166, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38277303

RESUMO

BACKGROUND: Parkinson's disease (PD) is a complex neurodegenerative disorder impacting everyday function and quality of life. Rehabilitation plays a crucial role in improving symptoms, function, and quality of life and reducing disability, particularly given the lack of disease-modifying agents and limitations of medications and surgical therapies. However, rehabilitative care is under-recognized and under-utilized in PD and often only utilized in later disease stages, despite research and guidelines demonstrating its positive effects. Currently, there is a lack of consensus regarding fundamental topics related to rehabilitative services in PD. OBJECTIVE: The goal of the international Parkinson's Foundation Rehabilitation Medicine Task Force was to develop a consensus statement regarding the incorporation of rehabilitation in PD care. METHODS: The Task Force, comprised of international multidisciplinary experts in PD and rehabilitation and people directly affected by PD, met virtually to discuss topics such as rehabilitative services, existing therapy guidelines and rehabilitation literature in PD, and gaps and needs. A systematic, interactive, and iterative process was used to develop consensus-based statements on core components of PD rehabilitation and discipline-specific interventions. RESULTS: The expert-based consensus statement outlines key tenets of rehabilitative care including its multidisciplinary approach and discipline-specific guidance for occupational therapy, physical therapy, speech language pathology/therapy, and psychology/neuropsychology across all PD stages. CONCLUSIONS: Rehabilitative interventions should be an essential component in the comprehensive treatment of PD, from diagnosis to advanced disease. Greater education and awareness of the benefits of rehabilitative services for people with PD and their care partners, and further evidence-based and scientific study are encouraged.


Assuntos
Pessoas com Deficiência , Terapia Ocupacional , Doença de Parkinson , Humanos , Qualidade de Vida , Fonoterapia
14.
Pediatrics ; 153(2)2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38174350

RESUMO

BACKGROUND AND OBJECTIVES: Drug-drug interactions (DDIs) can cause adverse drug events, but little is known about DDI exposure in children in the outpatient setting. This study aimed to determine the prevalence of major DDI exposure and factors associated with higher DDI exposure rates among children in an outpatient setting. METHODS: We performed a cross-sectional study of children aged 0 to 18 years with ≥1 ambulatory encounter, and ≥2 dispensed outpatient prescriptions study using the 2019 Marketscan Medicaid database. DDIs (exposure to a major DDI for ≥1 day) and the adverse physiologic effects of each DDI were identified using DrugBank's interaction database. Primary outcomes included the prevalence and rate of major DDI exposure. We used logistic regression to assess patient characteristics associated with DDI exposure. We examined the rate of DDI exposures per 100 children by adverse physiologic effects category, and organ-level effects (eg, heart rate-corrected QT interval prolongation). RESULTS: Of 781 019 children with ≥2 medication exposures, 21.4% experienced ≥1 major DDI exposure. The odds of DDI exposure increased with age and with medical and mental health complexity. Frequently implicated drugs included: Clonidine, psychiatric medications, and asthma medications. The highest adverse physiologic effect exposure rate per 100 children included: Increased drug concentrations (14.6), central nervous system depression (13.6), and heart rate-corrected QT interval prolongation (9.9). CONCLUSIONS: One in 5 Medicaid-insured children with ≥2 prescription medications were exposed to major DDIs annually, with higher exposures in those with medical or mental health complexity. DDI exposure places children at risk for negative health outcomes and adverse drug events, especially in the harder-to-monitor outpatient setting.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Pacientes Ambulatoriais , Criança , Humanos , Estudos Transversais , Medicaid , Interações Medicamentosas
15.
Mov Disord ; 39(1): 17-28, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38173220

RESUMO

BACKGROUND: Subjective cognitive complaints (SCCs) in Parkinson's disease (PD) are reported frequently, but their prevalence and association with changes on objective testing are not fully known. OBJECTIVE: We aimed to determine the prevalence, clinical correlates, and predictive value of SCCs in PD. METHODS: We conducted a systematic review and meta-analysis. From 204 abstracts, we selected 31 studies (n = 3441 patients), and from these, identified the prevalence, clinical features, associations with neuropsychiatric symptoms, and predictive values of SCCs in PD. RESULTS: The meta-analysis showed an SCC prevalence of 36%. This prevalence, however, was significantly moderated by study heterogeneity regarding female sex, disease severity, levodopa equivalent daily dosage, exclusion from the overall sample of patients with objective cognitive impairment, and measurement instrument. SCC prevalence did not differ between de novo and treated PD patients. SCCs were weakly and negligibly associated with cognitive changes on objective testing in cross-sectional studies. However, in cognitively healthy patients, SCCs had a risk ratio of 2.71 for later cognitive decline over a mean follow-up of 3.16 years. Moreover, SCCs were moderately related to co-occurring symptoms of depression, anxiety, or apathy and were more strongly related to these neuropsychiatric symptoms than objective cognitive functioning. CONCLUSION: Our analyses suggest that SCCs in patients with and without objective cognitive impairment are frequent, occurring in more than one third of PD patients. Establishing uniform measurement instruments for identifying PD-related SCCs is critical to understand their implications. Even in cases lacking evidence of objective cognitive impairment and where SCCs might reflect underlying neuropsychiatric symptoms, the possibility of later cognitive deterioration should not be excluded. Therefore, SCCs in PD patients warrant close monitoring for opportunities for targeted and effective interventions. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Transtornos Cognitivos , Disfunção Cognitiva , Doença de Parkinson , Humanos , Feminino , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Doença de Parkinson/psicologia , Estudos Transversais , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Cognição
16.
PLoS One ; 19(1): e0295410, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38215178

RESUMO

Documentation of adverse drug reactions (ADRs) is a key factor in guiding future prescribing. However, incomplete documentation is common and often fails to distinguish implicated drugs as true allergies. This in turn leads to unnecessary avoidance of implicated drug classes and may result in sub-optimal prescribing. Pharmacovigilance (PV) programs utilize a systematic approach to clarify ADR documentation and are known to improve patient safety. Yet it remains unclear if PV alters prescribing. Or, if the existence of the ADR documentation itself continues to prompt avoidance of implicated drugs. To address this, our work presents a retrospective cohort study assessing if clarification of antibiotic ADRs by a hospital-wide PV team was associated with future, safe, re-prescribing at a freestanding pediatric hospital in the midwestern United States. First, we compared the likelihood of future prescribing in an antibiotic class with an active ADR, as compared to alternative drug classes, between PV-clarified and non-clarified patients. Second, we assessed differences in adverse event rates 30-days after future prescribing based on PV clarification status. For robustness, analyses were performed on patients with ADRs in four antibiotic classes: penicillin-based beta-lactams (n = 45,642), sulfonamides/trimethoprim (n = 5,329), macrolides (n = 3,959), and glycopeptides (n = 622). Results illustrate that clarification of an ADR by PV was associated with an increased odds of future prescribing in the same drug class (Odds Ratio [95%-CI]): penicillin-based beta-lactams (1.59 [1.36-1.89]), sulfonamides/trimethoprim (2.29 [0.89-4.91]), macrolides (0.77 [0.33-1.61]), and glycopeptide (1.85 [1.12-3.20]). Notably, patients clarified by PV experienced no increase in the rate of adverse events within 30-days following the prescribing of antibiotics in the same class as an active ADR. Overall, this study provides strong evidence that PV reviews safely increase the rate of re-prescribing antibiotics even in the presence of an existing implicated drug ADR.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacovigilância , Criança , Humanos , Estudos Retrospectivos , Antibacterianos/efeitos adversos , Hospitais Pediátricos , Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Meio-Oeste dos Estados Unidos , Penicilinas , beta-Lactamas , Macrolídeos , Sulfonamidas , Trimetoprima
18.
Neuroinformatics ; 22(1): 75-87, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37981636

RESUMO

To simulate whole brain dynamics with only a few equations, biophysical, mesoscopic models of local neuron populations can be connected using empirical tractography data. The development of mesoscopic mean-field models of neural populations, in particular, the Adaptive Exponential (AdEx mean-field model), has successfully summarized neuron-scale phenomena leading to the emergence of global brain dynamics associated with conscious (asynchronous and rapid dynamics) and unconscious (synchronized slow-waves, with Up-and-Down state dynamics) brain states, based on biophysical mechanisms operating at cellular scales (e.g. neuromodulatory regulation of spike-frequency adaptation during sleep-wake cycles or anesthetics). Using the Virtual Brain (TVB) environment to connect mean-field AdEx models, we have previously simulated the general properties of brain states, playing on spike-frequency adaptation, but have not yet performed detailed analyses of other parameters possibly also regulating transitions in brain-scale dynamics between different brain states. We performed a dense grid parameter exploration of the TVB-AdEx model, making use of High Performance Computing. We report a remarkable robustness of the effect of adaptation to induce synchronized slow-wave activity. Moreover, the occurrence of slow waves is often paralleled with a closer relation between functional and structural connectivity. We find that hyperpolarization can also generate unconscious-like synchronized Up and Down states, which may be a mechanism underlying the action of anesthetics. We conclude that the TVB-AdEx model reveals large-scale properties identified experimentally in sleep and anesthesia.


Assuntos
Anestésicos , Encéfalo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Neurônios/fisiologia , Cabeça , Metodologias Computacionais , Modelos Neurológicos
19.
J Pediatr Pharmacol Ther ; 28(7): 643-648, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025152

RESUMO

PURPOSE: Etoposide, a topoisomerase II inhibitor used clinically to treat cancer, has been associated with severe anaphylactic infusion related adverse drug reactions (ADRs). In a previous study we identified a hydrophilic polyethersulfone filter as a possible cause of increased rates of pediatric etoposide infusion reactions. In this multidisciplinary follow-up analytical study, we aimed to assess the chemical structure of etoposide after passing through the same hydrophilic polyethersulfone filter. METHODS: An etoposide 0.4 mg/mL infusion was prepared under aseptic conditions and then passed through a standard IV infusion set with an in-line filter in place. Samples were taken in triplicate using a needle-less access system to include sampling sites directly from the IV bag port and from the IV tubing both before and after the in-line filter. Samples were diluted into mobile phase, then an aliquot was injected into a high-performance liquid chromatography mass spectrometry HPLC-MS (Thermo TSQ Quantum Ultra) system coupled to a Diode Array Detector (DAD) (Thermo Dionex Ultimate 3000). Etoposide was monitored using a selected reaction monitoring scan (SRM) of 606.2/228.8 and wavelengths of 210, 220, 254, and 280 nm for 30 minutes. RESULTS: No detectable differences were observed upon comparing the three samples. Based on these results, a chemical change in etoposide resulting from an in-line filter is unlikely to be the primary cause of increased rates of infusion reactions. CONCLUSION: Pharmacists working in healthcare systems, observe many ADRs, but rarely have the resources necessary to investigate the potential etiology or causality. This report highlights importance of multi-disciplinary collaboration to investigate serious ADRs.

20.
Front Med (Lausanne) ; 10: 1213889, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901413

RESUMO

Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN) is a predominantly drug-induced disease, with a mortality rate of 15-20%, that engages the expertise of multiple disciplines: dermatology, allergy, immunology, clinical pharmacology, burn surgery, ophthalmology, urogynecology, and psychiatry. SJS/TEN has an incidence of 1-5/million persons per year in the United States, with even higher rates globally. One of the challenges of SJS/TEN has been developing the research infrastructure and coordination to answer questions capable of transforming clinical care and leading to improved patient outcomes. SJS/TEN 2021, the third research meeting of its kind, was held as a virtual meeting on August 28-29, 2021. The meeting brought together 428 international scientists, in addition to a community of 140 SJS/TEN survivors and family members. The goal of the meeting was to brainstorm strategies to support the continued growth of an international SJS/TEN research network, bridging science and the community. The community workshop section of the meeting focused on eight primary themes: mental health, eye care, SJS/TEN in children, non-drug induced SJS/TEN, long-term health complications, new advances in mechanisms and basic science, managing long-term scarring, considerations for skin of color, and COVID-19 vaccines. The meeting featured several important updates and identified areas of unmet research and clinical need that will be highlighted in this white paper.

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