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1.
Artículo en Inglés | MEDLINE | ID: mdl-38946676

RESUMEN

Introduction: Studies show that acute cannabis use significantly increases heart rate (HR) and mildly raises blood pressure in the minutes following smoked or inhaled use of cannabis. However, less is known about how the THC concentration of the product or an individual's frequency of use (i.e., tolerance) may affect the magnitude of the change in HR. It is also relatively unexamined how the physical effects of increased HR after acute cannabis use relate to self-reported drug effects or blood THC levels. Aims: To describe the relationship between THC concentration of product used, self-reported subjective intoxication, THC blood levels, and frequency of cannabis use with the change in HR after acute cannabis use. Materials and Methods: Participants (n = 140) were given 15 min to smoke self-supplied cannabis ad libitum, HR was measured at baseline and an average of 2 min post-cannabis smoking. The ARCI-Marijuana scale and Visual Analog Scales (VAS) were administered, and blood samples were taken at both time points. Participants were asked about their frequency of use. Information about the product used was recorded from the package. Linear regression was used to analyze the relationship between changes in HR (post-pre cannabis use) and post-cannabis use HR, blood THC concentration, THC product concentration, frequency of use, and self-reported drug effect. Results: There was a significantly higher HR among those who smoked cannabis compared to the controls (p < 0.001), which did not significantly differ by frequency of use (p = 0.18). Higher concentration THC (extract) products did not produce a significantly different HR than lower concentration (flower) products (p = 0.096). VAS score was associated with an increase in HR (p < 0.05). Overall, blood THC levels were not significantly related to the change in HR (p = 0.69); however, when probed, there was a slight positive association among the occasional use group only. Discussion: Cardiovascular effects of cannabis consumption may not be as subject to tolerance with daily cannabis use and do not directly increase with THC concentration of the product. This is a departure from other effects (i.e., cognitive, subjective drug effects) where tolerance is well established. These findings also suggest that, at least among those with daily use, higher concentration THC products (>60%) do not necessarily produce cardiovascular physiological effects that are significantly more robust than lower concentration (<20%) products.

2.
Langmuir ; 40(23): 12027-12034, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38814003

RESUMEN

The ability to deposit pattern-specific molecular layers onto silicon with either regional p-/n-doping properties or that act as chemoselective resists for area-selective deposition is highly sought after in the bottom-up manufacturing of microelectronics. In this study, we demonstrate a simple protocol for the covalent attachment and patterning of a phosphorus-based dopant precursor onto silicon(100) functionalized with reactive carbene species. This method relies on selective surface reactions, which provide terminal functionalities that can be photochemically modified via ultraviolet-assisted contact printing between the carbene-functionalized substrate and an elastomeric stamp inked with the inorganic dopant precursor. X-ray photoelectron spectroscopy (XPS) analysis combined with scanning electron microscopy (SEM) imaging was used to characterize the molecule attachment and patterning ability of this technique. XPS spectra are indicative of the covalent bonding between phosphorus-containing molecules and the functionalized surface after both bulk solution-phase reaction and photochemical printing. SEM analysis of the corresponding printed features demonstrates the effective transfer of the phosphorus species in a patterned orientation matching that of the stamp pattern. This simple approach to patterning dopant precursors has the potential to inform the continued refinement of thin-film electronic, photonic, and quantum device manufacturing.

4.
Neuroradiology ; 66(7): 1225-1233, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38717474

RESUMEN

PURPOSE: Morning glory disc anomaly (MGDA) is a rare congenital ophthalmologic disorder. Historically it has been diagnosed fundoscopically, with little in the literature regarding its imaging findings. The purpose of this study is to further characterize the orbital and associated intracranial magnetic resonance imaging (MRI) findings of MGDA in our tertiary pediatric center. METHODS: A retrospective review was performed of fundoscopically-diagnosed cases of MGDA, that had been referred for MRI. All MRI studies were scrutinized for orbital and other intracranial abnormalities known to occur in association with MGDA. RESULTS: 18 of 19 cases of MGDA showed three characteristic MRI findings: funnel-shaped morphology of the posterior optic disc, abnormal soft tissue associated with the retrobulbar optic nerve, and effacement of adjacent subarachnoid spaces. The ipsilateral (intraorbital) optic nerve was larger in one patient and smaller in six. The ipsilateral optic chiasm was larger in two patients and smaller in one. CONCLUSION: This study represents a comprehensive radiological-led investigation into MGDA. It describes the most frequently-encountered MRI findings in MGDA and emphasizes the importance of MRI in this cohort, i.e., in distinguishing MGDA from other posterior globe abnormalities, in assessing the visual pathway, and in screening for associated intracranial abnormalities - skull base/cerebral, vascular, and facial. It hypothesizes neurocristopathy as an underlying cause of MGDA and its associations. Caliber abnormalities of the ipsilateral optic nerve and chiasm are a frequent finding in MGDA. Optic pathway enlargement should not be labeled "glioma". (239/250).


Asunto(s)
Imagen por Resonancia Magnética , Disco Óptico , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Niño , Disco Óptico/anomalías , Disco Óptico/diagnóstico por imagen , Preescolar , Lactante , Adolescente , Anomalías del Ojo/diagnóstico por imagen
5.
J Cannabis Res ; 6(1): 3, 2024 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-38308382

RESUMEN

BACKGROUND: Acute cannabis use has been demonstrated to slow reaction time and affect decision-making and short-term memory. These effects may have utility in identifying impairment associated with recent use. However, these effects have not been widely investigated among individuals with a pattern of daily use, who may have acquired tolerance. The purpose of this study was to examine the impact of tolerance to cannabis on the acute effects as measured by reaction time, decision-making (gap acceptance), and short-term memory. METHODS: Participants (ages 25-45) completed a tablet-based (iPad) test battery before and approximately 60 min after smoking cannabis flower. The change in performance from before to after cannabis use was compared across three groups of cannabis users: (1) occasional use (n = 23); (2) daily use (n = 31); or (3) no current use (n = 32). Participants in the occasional and daily use group self-administered ad libitum, by smoking or vaping, self-supplied cannabis flower with a high concentration of total THC (15-30%). RESULTS: The occasional use group exhibited decrements in reaction time (slowed) and short-term memory (replicated fewer shapes) from before to after cannabis use, as compared to the no-use group. In the gap acceptance task, daily use participants took more time to complete the task post-smoking cannabis as compared to those with no use or occasional use; however, the level of accuracy did not significantly change. CONCLUSIONS: The findings are consistent with acquired tolerance to certain acute psychomotor effects with daily cannabis use. The finding from the gap acceptance task which showed a decline in speed but not accuracy may indicate a prioritization of accuracy over response time. Cognitive and psychomotor assessments may have utility for identifying impairment associated with recent cannabis use.

6.
Clin Toxicol (Phila) ; 62(1): 10-18, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38421358

RESUMEN

INTRODUCTION: Cannabis intoxication may increase the risk of motor vehicle crashes. However, reliable methods of assessing cannabis intoxication are limited. The presence of eyelid tremors is among the signs of cannabis use identified under the Drug Evaluation and Classification Program of the International Association of Chiefs of Police. Our objectives were to assess the accuracy and replicability of identifying eyelid tremor as an indicator of recent cannabis smoking using a blinded, controlled study design. METHODS: Adult subjects (N = 103) were recruited into three groups based on their cannabis use history: daily, occasional, and no current cannabis use. Participants' closed eyelids were video recorded for 30 seconds by infrared videography goggles before and at a mean ± standard deviation time of 71.4 ± 4.6 minutes after the onset of a 15-minute interval of ad libitum cannabis flower smoking or vaping. Three observers with expertise in neuro-ophthalmology and medical toxicology were trained on exemplar videos of eyelids to reach a consensus on how to grade eyelid tremor. Without knowledge of subjects' cannabis use history or time point (pre- or post-smoking), observers reviewed each video for eyelid tremor graded as absent, slight, moderate, or severe. During subsequent data analysis, this score was further dichotomized as a consensus score of absent (absent/slight) or present (moderate/severe). RESULTS: Kappa and intraclass correlation coefficient statistics demonstrated moderate agreement among the coders, which ranged from 0.44-0.45 and 0.58-0.61, respectively. There was no significant association between recent cannabis use and the observers' consensus assessment that eyelid tremor was present, and cannabis users were less likely to have tremors (odds ratio: 0.75; 95 percent confidence interval: 0.25, 2.40). The assessment of eyelid tremor as an indicator of recent cannabis smoking had a sensitivity of 0.86, specificity of 0.18, and accuracy of 0.64. DISCUSSION: Eyelid tremor has fair sensitivity but poor specificity and accuracy for identification of recent cannabis use. Inter-rater reliability for assessment of eyelid tremor was moderate for the presence and degree of tremor. The weak association between recent cannabis use and eyelid tremor does not support its utility in identifying recent cannabis use. LIMITATIONS: Videos were recorded at only one time point after cannabis use. Adherence to abstinence could not be strictly supervised. Due to regulatory restrictions, we were unable to control the cannabis product used or administer a fixed Δ9-tetrahydrocannabinol dose. Participants were predominately non-Hispanic and White. CONCLUSIONS: In a cohort of participants with a range of cannabis use histories, acute cannabis smoking was not associated with the presence of eyelid tremor, regardless of cannabis use history, at 70 minutes post-smoking. Additional research is needed to identify the presence of eyelid tremor accurately, determine the relationship between cannabis dose and timeline in relation to last cannabis use to eyelid tremor, and determine how it should be, if at all, utilized for cannabis Drug Recognition Evaluator examinations.


Asunto(s)
Párpados , Alucinógenos , Abuso de Marihuana , Detección de Abuso de Sustancias , Adulto , Humanos , Cannabis , Párpados/efectos de los fármacos , Fumar Marihuana , Reproducibilidad de los Resultados , Temblor/inducido químicamente , Temblor/diagnóstico , Abuso de Marihuana/diagnóstico , Detección de Abuso de Sustancias/métodos
7.
ACS Appl Mater Interfaces ; 15(47): 55139-55149, 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-37965814

RESUMEN

The focus of this study was to demonstrate the vapor-phase halogenation of Si(100) and subsequently evaluate the inhibiting ability of the halogenated surfaces toward atomic layer deposition (ALD) of aluminum oxide (Al2O3). Hydrogen-terminated silicon ⟨100⟩ (H-Si(100)) was halogenated using N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), and N-iodosuccinimide (NIS) in a vacuum-based chemical process. The composition and physical properties of the prepared monolayers were analyzed by using X-ray photoelectron spectroscopy (XPS) and contact angle (CA) goniometry. These measurements confirmed that all three reagents were more effective in halogenating H-Si(100) over OH-Si(100) in the vapor phase. The stability of the modified surfaces in air was also tested, with the chlorinated surface showing the greatest resistance to monolayer degradation and silicon oxide (SiO2) generation within the first 24 h of exposure to air. XPS and atomic force microscopy (AFM) measurements showed that the succinimide-derived Hal-Si(100) surfaces exhibited blocking ability superior to that of H-Si(100), a commonly used ALD resist. This halogenation method provides a dry chemistry alternative for creating halogen-based ALD resists on Si(100) in near-ambient environments.

8.
Am J Public Health ; 113(12): 1332-1342, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37939329

RESUMEN

Background. The concentration of pharmacologically active tetrahydrocannabinol (THC) in cannabis products has been increasing over the past decade. Concerns about potential harmful health effects of using these increasingly higher-concentration products have led some states to consider regulation of cannabis product THC concentration. We conducted a scoping review of health effects of high-concentration cannabis products to inform policy on whether the THC concentrations of cannabis product should be regulated or limited. Objectives. We conducted a scoping review to (1) identify and describe human studies that explore the relationship of high-concentration cannabis products with any health outcomes in the literature and (2) create an interactive evidence map of the included studies to facilitate further analyses. Search Methods. An experienced medical information specialist designed a comprehensive search strategy of 7 electronic databases. Selection Criteria. We included human studies of any epidemiological design with no restrictions by age, sex, health status, country, or outcome measured that reported THC concentration or included a known high-concentration cannabis product. Data Collection and Analysis. We imported search results into Distiller SR, and trained coders conducted artificial intelligence‒assisted screening. We developed, piloted, and revised data abstraction forms. One person performed data abstraction, and a senior reviewer verified a subset. We provide a tabular description of study characteristics, including exposures and outcomes measured, for each included study. We interrogated the evidence map published in Tableau to answer specific questions and provide the results as text and visual displays. Main Results. We included 452 studies in the scoping review and evidence map. There was incomplete reporting of exposure characteristics including THC concentration, duration and frequency of use, and products used. The evidence map shows considerable heterogeneity among studies in exposures, outcomes, and populations studied. A limited number of reports provided data that would facilitate further quantitative synthesis of the results across studies. Conclusions. This scoping review and evidence map support strong conclusions concerning the utility of the literature for characterizing risks and benefits of the current cannabis marketplace and the research approaches followed in the studies identified. Relevance of the studies to today's products is limited. Public Health Implications. High-quality evidence to address the policy question of whether the THC concentration of cannabis products should be regulated is scarce. The publicly available interactive evidence map is a timely resource for other entities concerned with burgeoning access to high-concentration cannabis. (Am J Public Health. 2023;113(12):1332-1342. https://doi.org/10.2105/AJPH.2023.307414).


Asunto(s)
Cannabis , Humanos , Cannabis/efectos adversos , Inteligencia Artificial , Analgésicos , Salud Pública
9.
Circulation ; 148(16): e149-e184, 2023 10 17.
Artículo en Inglés | MEDLINE | ID: mdl-37721023

RESUMEN

In this focused update, the American Heart Association provides updated guidance for resuscitation of patients with cardiac arrest, respiratory arrest, and refractory shock due to poisoning. Based on structured evidence reviews, guidelines are provided for the treatment of critical poisoning from benzodiazepines, ß-adrenergic receptor antagonists (also known as ß-blockers), L-type calcium channel antagonists (commonly called calcium channel blockers), cocaine, cyanide, digoxin and related cardiac glycosides, local anesthetics, methemoglobinemia, opioids, organophosphates and carbamates, sodium channel antagonists (also called sodium channel blockers), and sympathomimetics. Recommendations are also provided for the use of venoarterial extracorporeal membrane oxygenation. These guidelines discuss the role of atropine, benzodiazepines, calcium, digoxin-specific immune antibody fragments, electrical pacing, flumazenil, glucagon, hemodialysis, hydroxocobalamin, hyperbaric oxygen, insulin, intravenous lipid emulsion, lidocaine, methylene blue, naloxone, pralidoxime, sodium bicarbonate, sodium nitrite, sodium thiosulfate, vasodilators, and vasopressors for the management of specific critical poisonings.


Asunto(s)
Reanimación Cardiopulmonar , Paro Cardíaco , Humanos , Antagonistas Adrenérgicos beta , American Heart Association , Benzodiazepinas , Digoxina , Paro Cardíaco/inducido químicamente , Paro Cardíaco/terapia , Estados Unidos
10.
Pediatrics ; 152(3)2023 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-37635689

RESUMEN

OBJECTIVE: The study characterizes cannabis toxicity in relation to tetrahydrocannabinol (THC) dose in pediatric edible cannabis ingestions. METHODS: This is a retrospective review of children aged <6 years presenting with edible cannabis ingestions of known THC dose within a pediatric hospital network (January 1, 2015-October 25, 2022). Cannabis toxicity was characterized as severe if patients exhibited severe cardiovascular (bradycardia, tachycardia/hypotension requiring vasopressors or intravenous fluids, other dysrhythmias), respiratory (respiratory failure, apnea, requiring oxygen supplementation), or neurologic (seizure, myoclonus, unresponsiveness, responsiveness to painful stimulation only, requiring intubation or sedation) effects. Cannabis toxicity was characterized as prolonged if patients required >6 hours to reach baseline. The relationship between THC dose and severe and prolonged toxicity was explored using multivariable logistic regression and receiver operator characteristic curve analyses. RESULTS: Eighty patients met inclusion. The median age was 2.9 years. The median THC ingestion was 2.1 mg/kg. Severe and prolonged toxicity was present in 46% and 74%, respectively. THC dose was a significant predictor of severe (adjusted odds ratio 2.9, 95% confidence interval: 1.8-4.7) and prolonged toxicity (adjusted odds ratio 3.2, 95% confidence interval: 1.6-6.5), whereas age and sex were not. Area under the curve was 92.9% for severe and 87.3% for prolonged toxicity. THC ingestions of ≥1.7 mg/kg can predict severe (sensitivity 97.3%) and prolonged toxicity (sensitivity 75.4%). CONCLUSIONS: The THC dose of edible cannabis correlates to the degree of toxicity in children <6 years old. The threshold of 1.7 mg/kg of THC may guide medical management and preventive regulations.


Asunto(s)
Anestesia , Cannabis , Humanos , Niño , Preescolar , Dronabinol , Bradicardia , Ingestión de Alimentos
11.
J Gen Intern Med ; 38(12): 2726-2733, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37340250

RESUMEN

BACKGROUND: Cannabis may be a substitute for opioids but previous studies have found conflicting results when using data from more recent years. Most studies have examined the relationship using state-level data, missing important sub-state variation in cannabis access. OBJECTIVE: To examine cannabis legalization on opioid use at the county level, using Colorado as a case study. Colorado allowed recreational cannabis stores in January 2014. Local communities could decide whether to allow dispensaries, creating variation in the level of exposure to cannabis outlets. DESIGN: Observational, quasi-experimental design exploiting county-level variation in allowance of recreational dispensaries. SUBJECTS: Colorado residents MEASURES: We use licensing information from the Colorado Department of Revenue to measure county-level exposure to cannabis outlets. We use the state's Prescription Drug Monitoring Program (2013-2018) to construct opioid-prescribing measures of number of 30-day fills and total morphine equivalents, both per county resident per quarter. We construct outcomes of opioid-related inpatient visits (2011-2018) and emergency department visits (2013-2018) with Colorado Hospital Association data. We use linear models in a differences-in-differences framework that accounts for the varying exposure to medical and recreational cannabis over time. There are 2048 county-quarter observations used in the analysis. RESULTS: We find mixed evidence of cannabis exposure on opioid-related outcomes at the county level. We find increasing exposure to recreational cannabis is associated with a statistically significant decrease in number of 30-day fills (coefficient: -117.6, p-value<0.01) and inpatient visits (coefficient: -0.8, p-value: 0.03), but not total MME nor ED visits. Counties with no medical exposure prior to recreational legalization experience greater reductions in the number of 30-day fills and MME than counties with prior medical exposure (p=0.02 for both). CONCLUSIONS: Our mixed findings suggest that further increases in cannabis beyond medical access may not always reduce opioid prescribing or opioid-related hospital visits at a population level.


Asunto(s)
Analgésicos Opioides , Cannabis , Humanos , Colorado/epidemiología , Cannabis/efectos adversos , Pautas de la Práctica en Medicina , Hospitales , Agonistas de Receptores de Cannabinoides
12.
Clin Toxicol (Phila) ; 61(5): 355-362, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-37293900

RESUMEN

INTRODUCTION: Cannabis use is a growing concern in transportation and workplace incidents. Because Δ9-tetrahydrocannabinol is detectable after acute psychoactive effects have resolved, it has limitations as an indicator of recent usage or potential impairment. METHODS: In an observational study of driving and psychomotor performance, we measured whole blood Δ9-tetrahydrocannabinol plus its metabolites 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol by liquid chromatography with tandem mass spectrometry at baseline and 30 min after starting a 15-minute interval of smoking cannabis in 24 occasional and 32 daily cannabis smokers. We calculated two blood cannabinoid molar metabolite ratios: 1) [Δ9-tetrahydrocannabinol] to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol] and 2) ([Δ9-tetrahydrocannabinol] + [11-hydroxy-Δ9-tetrahydrocannabinol]) to [11-nor-9-carboxy-Δ9-tetrahydrocannabinol]. We compared these to blood [Δ9-tetrahydrocannabinol] alone as indicators of recent cannabis smoking. RESULTS: Median Δ9-tetrahydrocannabinol concentrations increased from 0 ( 0.38). By comparison, a cut-point for Δ9-tetrahydrocannabinol of 5.3 µg/L yielded 88% specificity, 73% sensitivity, and 80% accuracy. CONCLUSIONS: In occasional and daily users, the blood cannabinoid molar metabolite ratios were superior to whole blood Δ9-tetrahydrocannabinol as indicators of recent cannabis smoking. We recommend measurement and reporting of Δ9-tetrahydrocannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, and their molar metabolite ratios in forensic and safety investigations.


Asunto(s)
Cannabinoides , Cannabis , Alucinógenos , Fumar Marihuana , Humanos , Dronabinol , Detección de Abuso de Sustancias/métodos , Agonistas de Receptores de Cannabinoides
13.
Clin Toxicol (Phila) ; 61(5): 363-369, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36939145

RESUMEN

INTRODUCTION: The determination of recent cannabis use is of forensic interest in the investigation of automotive crashes, workplace incidents and other mishaps. Because Δ9-tetrahydrocannabinol may persist in blood after psychoactive effects of intoxication resolve, particularly in regular users, short-lived minor cannabinoids such as cannabigerol have merited examination as adjunct indicators of recent cannabis inhalation. METHODS: As part of an observational cohort study, whole blood cannabinoids including cannabigerol were measured in whole blood by liquid chromatography with tandem mass spectrometry at baseline, and 30 minutes after initiation of a 15-minute supervised interval of ad libitum cannabis smoking in occasional (1-2 days/week over the past 30 days) (n = 24) and daily cannabis smokers (n = 32). Per protocol, subjects self-reported abstention from inhaling cannabis (>8 h) or ingesting cannabis (>12 h) prior to baseline measurement. RESULTS: At baseline, none of the occasional users had detectable cannabigerol (limit of detection = 0.2 µg/L), whereas cannabigerol was detectable post-smoking in 7 of 24 (29%). Among daily cannabis users, 2 of 32 (6%) had detectable cannabigerol at baseline, increasing to 21 of 32 (66%) post-smoking. The odds ratio for recent cannabis smoking associated with a detectable cannabigerol was 27 (95% confidence interval: 6.6, 110.3). In this mixed cohort of occasional and daily cannabis users, receiver operator characteristic curve analysis indicated that whole blood cannabigerol concentration of ≥ 0.2 µg/L had 96% specificity, 50% sensitivity, and 73% accuracy for identifying a 15-minute interval of ad libitum cannabis smoking initiated 30 minutes earlier. Post smoking blood Δ9-tetrahydrocannabinol (median = 5.6 µg/L in occasional users, 21.3 µg/L in daily users) was significantly correlated with post-smoking cannabigerol (P < 0.0001). CONCLUSION: Whole blood cannabigerol may have forensic utility as a highly specific albeit insensitive biomarker of recent cannabis smoking.


Asunto(s)
Cannabinoides , Cannabis , Alucinógenos , Fumar Marihuana , Humanos , Dronabinol , Detección de Abuso de Sustancias/métodos , Agonistas de Receptores de Cannabinoides , Biomarcadores
14.
J Clin Oncol ; 41(18): 3339-3351, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-36952634

RESUMEN

PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) remains a lethal disease with current standard-of-care therapies. Homologous recombination repair (HRR) gene alterations, including BRCA1/2 alterations, can sensitize cancer cells to poly (ADP-ribose) polymerase inhibition, which may improve outcomes in treatment-naïve mCRPC when combined with androgen receptor signaling inhibition. METHODS: MAGNITUDE (ClinicalTrials.gov identifier: NCT03748641) is a phase III, randomized, double-blinded study that evaluates niraparib and abiraterone acetate plus prednisone (niraparib + AAP) in patients with (HRR+, n = 423) or without (HRR-, n = 247) HRR-associated gene alterations, as prospectively determined by tissue/plasma-based assays. Patients were assigned 1:1 to receive niraparib + AAP or placebo + AAP. The primary end point, radiographic progression-free survival (rPFS) assessed by central review, was evaluated first in the BRCA1/2 subgroup and then in the full HRR+ cohort, with secondary end points analyzed for the full HRR+ cohort if rPFS was statistically significant. A futility analysis was preplanned in the HRR- cohort. RESULTS: Median rPFS in the BRCA1/2 subgroup was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.6 v 10.9 months; hazard ratio [HR], 0.53; 95% CI, 0.36 to 0.79; P = .001). In the overall HRR+ cohort, rPFS was significantly longer in the niraparib + AAP group compared with the placebo + AAP group (16.5 v 13.7 months; HR, 0.73; 95% CI, 0.56 to 0.96; P = .022). These findings were supported by improvement in the secondary end points of time to symptomatic progression and time to initiation of cytotoxic chemotherapy. In the HRR- cohort, futility was declared per the prespecified criteria. Treatment with niraparib + AAP was tolerable, with anemia and hypertension as the most reported grade ≥ 3 adverse events. CONCLUSION: Combination treatment with niraparib + AAP significantly lengthened rPFS in patients with HRR+ mCRPC compared with standard-of-care AAP.[Media: see text].


Asunto(s)
Acetato de Abiraterona , Neoplasias de la Próstata Resistentes a la Castración , Masculino , Humanos , Acetato de Abiraterona/efectos adversos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Proteína BRCA1 , Proteína BRCA2 , Prednisona , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos
17.
Ann Pharmacother ; 57(1): 36-43, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35587124

RESUMEN

BACKGROUND: Acetaminophen overdose is a leading cause of liver failure, and a leading cause of pediatric poisoning requiring hospital admission. The antidote, N-acetylcysteine (NAC), is traditionally administered as a three-bag intravenous infusion. Despite its efficacy, NAC is associated with high incidence of nonallergic anaphylactoid reactions (NAARs). Adult evidence demonstrates that alternative dosing regimens decrease NAARs and medication errors (MEs). OBJECTIVES: To compare NAARs and MEs associated with two- versus three-bag NAC for acetaminophen overdose in a pediatric population. METHODS: This is a retrospective observational cohort study comparing pediatric patients who received three- versus two-bag NAC for acetaminophen toxicity. The primary outcome was incidence of NAARs. Secondary outcomes were rates of MEs and relevant hospital outcomes (length of stay [LOS], intensive care unit (ICU) admission, liver transplant, death). RESULTS: Two hundred forty-three patients met inclusion criteria (median age of 15 years): 150 (62%) three-bag NAC and 93 (38%) two-bag NAC. There was no difference in overall NAARs (p = 0.54). Fewer cutaneous NAARs were observed in the two-bag group, three-bag: 15 (10%), two-bag: 2 (2%), p = 0.02. MEs were significantly decreased with the two-bag regimen, three-bag: 59 (39%), two-bag: 21 (23%), p = 0.01. No statistical differences were observed in LOS, ICU admissions, transplant, or death. CONCLUSION AND RELEVANCE: A significant decrease in cutaneous NAARs and MEs was observed in pediatric patients by combining the first two bags of the traditional three-bag NAC regimen. In pediatric populations, a two-bag NAC regimen for acetaminophen overdose may improve medication tolerance and safety.


Asunto(s)
Analgésicos no Narcóticos , Sobredosis de Droga , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Adulto , Niño , Humanos , Adolescente , Acetilcisteína/uso terapéutico , Acetaminofén/uso terapéutico , Antídotos/uso terapéutico , Estudios de Cohortes , Sobredosis de Droga/tratamiento farmacológico , Estudios Retrospectivos , Analgésicos no Narcóticos/uso terapéutico
18.
Chemphyschem ; 24(7): e202200724, 2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-36516050

RESUMEN

As atomic layer deposition (ALD) emerges as a method to fabricate architectures with atomic precision, emphasis is placed on understanding surface reactions and nucleation mechanisms. ALD of titanium dioxide with TiCl4 and water has been used to investigate deposition processes in general, but the effect of surface termination on the initial TiO2 nucleation lacks needed mechanistic insights. This work examines the adsorption of TiCl4 on Cl-, H-, and HO- terminated Si(100) and Si(111) surfaces to elucidate the general role of different surface structures and defect types in manipulating surface reactivity of growth and non-growth substrates. The surface sites and their role in the initial stages of deposition are examined by X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). Density functional theory (DFT) computations of the local functionalized silicon surfaces suggest oxygen-containing defects are primary drivers of selectivity loss on these surfaces.

19.
Heliyon ; 8(11): e11239, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36339771

RESUMEN

Human activities significantly contribution to the yearly generated plastic wastes. Moreover, the enormous increase in face masks and face shields caused by the emergence of the COVID-19 pandemic has doubled the generated plastic wastes. Although there is an added benefit of using plastic waste in construction, the cost associated with their application, specifically the face mask, has not been addressed. This paper presents a simplified and rapid estimation of the cost associated with the collection, processing, and application of face masks in hot-mix asphalt (HMA) pavements. Two scenarios, mask modified asphalt pavement and conventional asphalt pavement, are considered. The total cost is based on market price and prices from waste management facilities and plastic processing companies. Life Cycle Cost Analysis (LCCA) is used to evaluate the long-term costs of mask modified asphalt pavement and conventional asphalt pavement. Results show that no significant difference in initial total cost between the two scenarios for pavement sections with lengths less than 500m and the number of lanes less than 6. The difference in total cost begins with lengths greater than 500 m for 5 and 6 Lanes. Despite the higher initial costs for the mask modified asphalt pavement, the LCCA shows that there is a 29% maintenance cost reduction over the 40 years life cycle of the asphalt pavement. The use of LCCA shows the benefit of the selection of the most cost-effective strategy and how the use of mask modified asphalt pavement over the conventional asphalt pavement can save money over the life cycle of the asphalt and improve rutting and stiffens.

20.
J Clean Prod ; 375: 134086, 2022 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-36160313

RESUMEN

The COVID-19 pandemic not only poses an unprecedented threat to global health but also severely disrupts the natural environment and ecosystems. Mitigating the adverse impacts of plastic-based personal protective equipment (PPE) waste requires the cooperation of professionals from various fields. This paper discusses a novel, cleaner approach to soil stabilisation by repurposing the nitrile gloves into a sustainable road material to improve the mechanical properties of expansive clay soil as pavement subgrade. For the first time, extensive geotechnical testings, including standard compaction, unconfined compressive strength (UCS), unsoaked California bearing ratio (CBR), repeated load triaxial (RLT), and swelling-shrinkage tests, were carried out to investigate the engineering performance of different proportions of the shredded nitrile gloves (SNG) (e.g., 1%, 1.5%, 2%) were blended with expansive clay (EC). In addition, surface roughness, scanning electron microscopy (SEM), and X-ray micro-CT analyses were conducted, and images were obtained to study the microstructural modification of the EC-SNG mixtures. The experimental results indicated that the blend of expansive clay with SNG helped in increasing the compressive strength, resilient modulus, and CBR and assisted in reducing the swelling and shrinkage of the soil. SEM and surface roughness analyses indicated the interaction between the soil matrix interface and the rough surface of the SNG. The main reasons for increasing the strength and stability of clay soil could be attributed to the high tensile strength of the SNG and the formation of the three-dimensional grid, and friction between the soil particles and SNG. According to the X-ray micro-CT test results, the incorporation of SNG led to an increase in closed porosity.

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