RESUMO
BACKGROUND: Despite recent advances in lung cancer therapeutics and improving overall survival, disparities persist among socially disadvantaged populations. This study aims to determine the effects of neighborhood deprivation indices (NDI) on lung cancer mortality. This is a multicenter retrospective cohort study assessing the relationship between NDI and overall survival adjusted for age, disease stage, and DNA methylation among biopsy-proven lung cancer patients. State-specific NDI for each year of sample collection were computed at the U.S. census tract level and dichotomized into low- and high-deprivation. RESULTS: A total of 173 non small lung cancer patients were included, with n = 85 (49%) and n = 88 (51%) in the low and high-deprivation groups, respectively. NDI was significantly higher among Black patients when compared with White patients (p = 0.003). There was a significant correlation between DNA methylation and stage for HOXA7, SOX17, ZFP42, HOXA9, CDO1 and TAC1. Only HOXA7 DNA methylation was positively correlated with NDI. The high-deprivation group had a statistically significant shorter survival than the low-deprivation group (p = 0.02). After adjusting for age, race, stage, and DNA methylation status, belonging to the high-deprivation group was associated with higher mortality with a hazard ratio of 1.81 (95%CI: 1.03-3.19). CONCLUSIONS: Increased neighborhood-level deprivation may be associated with liquid biopsy DNA methylation, shorter survival, and increased mortality. Changes in health care policies that consider neighborhood-level indices of socioeconomic deprivation may enable a more equitable increase in lung cancer survival.
Assuntos
Metilação de DNA , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/patologia , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Características da Vizinhança , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Estados Unidos/epidemiologia , Fatores Socioeconômicos , Características de ResidênciaRESUMO
BACKGROUND: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) of the chest of eligible patients remains low. Accordingly, augmentation of appropriate LCS referrals by primary care providers (PCPs) was sought. METHODS: The quality improvement (QI) project was performed between April 2021 and June 2022. It incorporated patient education, shared decision-making (SDM) with PCPs, and tracking of initial LDCT completion. In each case, lag time (LT) to LCS and pack-years (PYs) were calculated from initial LCS eligibility. The cohort's scores were compared to national scores. Patient zip codes were used to create a geographic map of our cohort for comparison with public health data. RESULTS: An immediate and sustained increase in weekly LCS referrals from PCPs was recorded. Of 337 initial referrals, 95% were men, consisting of 66.2% Black, 28.4% White, and 5.4% other. Mean PY was less for minorities (45.3 vs. 37.3 years; p = .0002) but mean LT was greater for Whites (7.9 vs. 6.2 years; p = .03). Twenty-five percent of veterans failed to report to their scheduled screening, and two declined referrals. Notably, most no-show patients lived in transit deserts. Furthermore, Lung-RADS scores 4B/4X were more than double the expected prevalence (p = .008). CONCLUSIONS: The PCPs in this study successfully augmented LCS referrals. A substantial proportion of these patients were no-shows, and our data suggest complex racial and socioeconomic factors as contributing variables. In addition, a higher-than-expected number of initial Lung-RADS scores 4B/4X were reported. A large, multisite QI project is warranted to address overcoming potential transportation barriers in high-risk patient populations.
Assuntos
Detecção Precoce de Câncer , Neoplasias Pulmonares , Masculino , Humanos , Feminino , Detecção Precoce de Câncer/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Tomografia Computadorizada por Raios X/métodos , Fatores de Risco , Atenção Primária à Saúde , Programas de Rastreamento/métodosRESUMO
BACKGROUND: While several safe and effective COVID-19 vaccines have been available since December 2020, many eligible individuals choose to remain unvaccinated. This vaccine hesitancy is an important factor affecting our ability to combat the COVID-19 pandemic. METHODS: The objective of the study was to examine the attitudes and willingness among US Veterans toward receiving COVID-19 vaccination. The study used a quantitative qualitative mixed methods design with a telephone survey and then in-depth interviews in a subset of those surveyed. Participants were unvaccinated Veterans (N = 184) selected randomly from a registry of patients who had received VA healthcare during the pandemic and had a diagnostic test for COVID-19. The primary outcome was willingness to accept COVID-19 vaccination. Survey data collection and in-depth interviews were conducted by telephone. Analyses of the survey data compared the primary outcome with demographics, clinical data, and survey responses using bivariate and multiple regression analyses. A subset (N = 10) of those surveyed, participated in an in-depth interview. Interview transcripts were analyzed to derive themes using qualitative content analysis. RESULTS: Almost 40% of participants disagreed they would receive a COVID-19 vaccine. Participants who were younger, female, and had fewer comorbid conditions were more likely (P < 0.05) to disagree with COVID-19 vaccination. In multiple regression analysis, willingness to accept vaccination was associated with reliance on a doctor or family member's recommendation and with a belief that vaccines are effective. In-depth interviews revealed several barriers to COVID-19 vaccination, including lack of trust in the government and vaccine manufacturers, concerns about the speed of vaccine development, fear of side effects, and fear the vaccine was a tool of racism. CONCLUSIONS: This study illustrates the complexity of patients' deliberation about COVID-19 vaccination and may help physicians and other health care providers understand patients' perspectives about COVID-19 vaccination. The results highlight the importance of patients' trust in physicians, healthcare organizations, pharmaceutical manufacturers and the government when making health decisions.
Assuntos
COVID-19 , Veteranos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Feminino , Humanos , Masculino , Pandemias , Aceitação pelo Paciente de Cuidados de Saúde , Inquéritos e QuestionáriosRESUMO
PURPOSE OF REVIEW: Sarcoidosis is a poorly understood multisystem granulomatous disease that frequently involves the lungs but can affect any organ system. In this review, we summarize recent developments in the understanding of the immune dysregulation seen in sarcoidosis and propose a new expanded definition of human autoimmunity in sarcoidosis, and the implications it would have on treating sarcoidosis with targeted immunotherapy regimens in the future. RECENT FINDINGS: Sarcoidosis has been linked to infectious organisms like Mycobacterium and Cutibacterium, and certain manifestations of sarcoidosis have been linked to specific HLA alleles, but the overall pathogenesis remains uncertain. Sarcoidosis patients have similar patterns of cellular immune dysregulation seen in other autoimmune diseases like rheumatoid arthritis, and recent large-scale population studies show that sarcoidosis frequently presents with other autoimmune diseases. SUMMARY: Advancements in the understanding of sarcoidosis support its consideration as an autoimmune disease. Sarcoidosis patients carry a higher risk of comorbid autoimmune conditions which offers an excellent opportunity to further understand autoimmunity and explore biologic therapies in sarcoidosis treatment, and furthermore will better targeted immunotherapy regimens for sarcoidosis patients in the future.
Assuntos
Doenças Autoimunes , Sarcoidose , Alelos , Autoimunidade , Humanos , Sarcoidose/genética , Sarcoidose/terapiaRESUMO
A large-scale outbreak of life-threatening, inhaled synthetic cannabinoids (Spice/K2)-associated coagulopathy with bleeding complications was recently reported in Illinois. The causative agents were brodifacoum, difenacoum, and bromadiolone, potent, long-acting, 4-hydroxycoumarin anticoagulant rodenticides (LAAR) that were mixed with Spice/K2 products procured and then inhaled by the victims. We report on 3 poisoned patients who reside in underserved, socioeconomically disadvantaged neighborhoods of Chicago that were admitted and treated successfully at two inner-city, tertiary care hospitals in Chicago. The patients were discharged from the hospitals on daily long-term high-dose oral vitamin K1 (VK1), provided free of charge. However, 2 patients were lost to follow-up prior to safe discontinuation of oral VK1 therapy. The third patient was treated and followed successfully for 7 months when VK1 was discontinued. We conclude that prolonged oral VK1 therapy and follow-up of acute, life-threatening LAAR poisoning are variable and present challenges to healthcare providers. Appropriate practice guidelines to improve patient access and adherence to daily high-dose oral VK1 therapy and follow-up should be developed and implemented.
Assuntos
Anticoagulantes/intoxicação , Antifibrinolíticos/administração & dosagem , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Canabinoides , Hemorragia/tratamento farmacológico , Cooperação do Paciente , Vitamina K 1/administração & dosagem , 4-Hidroxicumarinas/intoxicação , Administração por Inalação , Adulto , Assistência ao Convalescente , Antifibrinolíticos/uso terapêutico , Transtornos da Coagulação Sanguínea/induzido quimicamente , Chicago , Feminino , Hemorragia/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Perda de Seguimento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Medicamentos Sintéticos , Vitamina K 1/uso terapêuticoRESUMO
Localized surface plasmon resonance (LSPR) spectroscopy is an effective tool for sensitive, affordable, and label-free biosensing. LSPR transducers based on nanoparticulate Au films have been applied to biosensing of receptor-analyte interactions, employing primarily thiolated receptors for constructing biorecognition interfaces on nanostructured Au surfaces. This popular method suffers from a major drawback, that is, the need to prepare a thiolated receptor for each system used, which is typically synthetically complex and time-consuming. Herein, we present an alternative approach based on the click reaction between azide and terminal alkyne, which avoids the need to synthesize thiol-derivatized receptors and is applicable to the heterogeneous morphology of LSPR transducers. The receptors are tethered with an alkyne group, which is considerably simpler than thiolation, while producing a stable product. The transducer surface is modified with a layer of a commercial long-chain thiol-azide molecule, then clicked with an alkyne-dertivatized receptor to produce the biorecognition interface. This method is employed for immobilization of four different alkyne-bearing receptor molecules on Au nano-island film based LSPR transducers, followed by testing of their performance in biorecognition of specific analytes using LSPR and FTIR spectroscopies. The results establish the usefulness of click chemistry for the preparation of biorecognition interfaces on nanostructured LSPR transducers.
RESUMO
Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.
Assuntos
4-Hidroxicumarinas/toxicidade , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Colesterol/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/química , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Animais , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , RatosRESUMO
Triggering receptors expressed on myeloid cell-1 (TREM-1) is a superimmunoglobulin receptor expressed on myeloid cells. Synergy between TREM-1 and Toll-like receptor amplifies the inflammatory response; however, the mechanisms by which TREM-1 accentuates inflammation are not fully understood. In this study, we investigated the role of TREM-1 in a model of LPS-induced lung injury and neutrophilic inflammation. We show that TREM-1 is induced in lungs of mice with LPS-induced acute neutrophilic inflammation. TREM-1 knockout mice showed an improved survival after lethal doses of LPS with an attenuated inflammatory response in the lungs. Deletion of TREM-1 gene resulted in significantly reduced neutrophils and proinflammatory cytokines and chemokines, particularly IL-1ß, TNF-α, and IL-6. Physiologically deletion of TREM-1 conferred an immunometabolic advantage with low oxygen consumption rate (OCR) sparing the respiratory capacity of macrophages challenged with LPS. Furthermore, we show that TREM-1 deletion results in significant attenuation of expression of miR-155 in macrophages and lungs of mice treated with LPS. Experiments with antagomir-155 confirmed that TREM-1-mediated changes were indeed dependent on miR-155 and are mediated by downregulation of suppressor of cytokine signaling-1 (SOCS-1) a key miR-155 target. These data for the first time show that TREM-1 accentuates inflammatory response by inducing the expression of miR-155 in macrophages and suggest a novel mechanism by which TREM-1 signaling contributes to lung injury. Inhibition of TREM-1 using a nanomicellar approach resulted in ablation of neutrophilic inflammation suggesting that TREM-1 inhibition is a potential therapeutic target for neutrophilic lung inflammation and acute respiratory distress syndrome (ARDS).
Assuntos
Lesão Pulmonar/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , MicroRNAs/genética , Receptores Imunológicos/metabolismo , Animais , Citocinas/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Lesão Pulmonar/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Células Mieloides/efeitos dos fármacos , Células Mieloides/metabolismo , Nanomedicina/métodos , RNA Interferente Pequeno/metabolismo , Receptor Gatilho 1 Expresso em Células MieloidesRESUMO
BACKGROUND: The impact of local anesthetics on the regulation of glucose homeostasis by protein kinase B (Akt) and 5'-adenosine monophosphate-activated protein kinase (AMPK) is unclear but important because of the implications for both local anesthetic toxicity and its reversal by IV lipid emulsion (ILE). METHODS: Sprague-Dawley rats received 10 mg/kg bupivacaine over 20 s followed by nothing or 10 ml/kg ILE (or ILE without bupivacaine). At key time points, heart and kidney were excised. Glycogen content and phosphorylation levels of Akt, p70 s6 kinase, s6, insulin receptor substrate-1, glycogen synthase kinase-3ß, AMPK, acetyl-CoA carboxylase, and tuberous sclerosis 2 were quantified. Three animals received Wortmannin to irreversibly inhibit phosphoinositide-3-kinase (Pi3k) signaling. Isolated heart studies were conducted with bupivacaine and LY294002-a reversible Pi3K inhibitor. RESULTS: Bupivacaine cardiotoxicity rapidly dephosphorylated Akt at S473 to 63 ± 5% of baseline and phosphorylated AMPK to 151 ± 19%. AMPK activation inhibited targets downstream of mammalian target of rapamycin complex 1 via tuberous sclerosis 2. Feedback dephosphorylation of IRS1 to 31 ± 8% of baseline sensitized Akt signaling in hearts resulting in hyperphosphorylation of Akt at T308 and glycogen synthase kinase-3ß to 390 ± 64% and 293 ± 50% of baseline, respectively. Glycogen accumulated to 142 ± 7% of baseline. Irreversible inhibition of Pi3k upstream of Akt exacerbated bupivacaine cardiotoxicity, whereas pretreating with a reversible inhibitor delayed the onset of toxicity. ILE rapidly phosphorylated Akt at S473 and T308 to 150 ± 23% and 167 ± 10% of baseline, respectively, but did not interfere with AMPK or targets of mammalian target of rapamycin complex 1. CONCLUSION: Glucose handling by Akt and AMPK is integral to recovery from bupivacaine cardiotoxicity and modulation of these pathways by ILE contributes to lipid resuscitation.
Assuntos
Anestésicos Locais/toxicidade , Bupivacaína/toxicidade , Emulsões Gordurosas Intravenosas/farmacologia , Coração/efeitos dos fármacos , Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Período de Recuperação da Anestesia , Animais , Western Blotting , Cardiotoxicidade/metabolismo , Modelos Animais de Doenças , Sinergismo Farmacológico , Emulsões Gordurosas Intravenosas/metabolismo , Quinase 3 da Glicogênio Sintase/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Técnicas In Vitro , Miocárdio/metabolismo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Galvanic replacement reactions (GRRs) on nanoparticles (NPs) are typically performed between two metals, i.e., a solid metal NP and a replacing salt solution of a more noble metal. The solution pH in GRRs is commonly considered an irrelevant parameter. Yet, the solution pH plays a major role in GRRs involving metal oxide NPs. Here, Cu(2)O nanocrystals (NCs) are studied as galvanic replacement (GR) precursors, undergoing replacement by gold and palladium, with the resulting nanostructures showing a strong dependence on the pH of the replacing metal salt solution. GRRs are reported for the first time on supported (chemically deposited) oxide NCs and the results are compared with those obtained with corresponding colloidal systems. Control of the pH enables production of different nanostructures, from metal-decorated Cu(2)O NCs to uniformly coated Cu(2)O-in-metal (Cu(2)O@Me) core-shell nanoarchitectures. Improved metal nucleation efficiencies at low pHs are attributed to changes in the Cu(2)O surface charge resulting from protonation of the oxide surface. GR followed by etching of the Cu(2)O cores provides metal nanocages that collapse upon drying; the latter is prevented using a sol-gel silica overlayer stabilizing the metal nanocages. Metal-replaced Cu(2)O NCs and their corresponding stabilized nanostructures may be useful as photocatalysts, electrocatalysts, and nanosensors.
RESUMO
INTRODUCTION: Brodifacoum (BDF) is a superwarfarin that is used primarily as a rodenticide. There have been increasing numbers of reports of human cases of accidental or intentional BDF ingestion with high mortality rate. Its broad availability and high lethality suggest that BDF should be considered a potential chemical threat. Currently, there is no biomarker for early detection of BDF ingestion in humans; patients typically present with severe coagulopathy. Since we demonstrated earlier that warfarin can induce acute kidney injury with hematuria, we tested whether BDF would also lead to change in urinary biomarkers. MATERIAL AND METHODS: BDF was administered to Sprague Dawley rats via oral gavage. N-acetylcysteine (NAC) was given per os in drinking water 24 h prior to BDF. Urinalysis was performed at different times after BDF administration. Anticoagulation and serum creatinine levels were analyzed in the blood. RESULTS: We observed that within a few hours the animals developed BDF-dose-dependent transient hemoglobinuria, which ceased within 24 h. This was accompanied by a transient decrease in hematocrit, gross hemolysis and an increase in free hemoglobin in the serum. At later times, animals developed true hematuria with red blood cells in the urine, which was associated with BDF anticoagulation. NAC prevented early hemoglobinuria, but not late hematuria associated with BDF. CONCLUSIONS: We propose that transient early hemoglobinuria (associated with oxidative stress) with consecutive late hematuria (associated with anticoagulation) are novel biomarkers of BDF poisoning, and they can be used in clinical setting or in mass casualty with BDF to identify poisoned patients.
Assuntos
4-Hidroxicumarinas/intoxicação , Hematúria/induzido quimicamente , Hemoglobinúria/induzido quimicamente , Rodenticidas/intoxicação , Acetilcisteína/farmacologia , Animais , Biomarcadores/urina , Progressão da Doença , Sequestradores de Radicais Livres/farmacologia , Hemoglobinas/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To determine whether intraosseous infusion of a lipid emulsion reverses cardiac pharmacotoxicity in anaesthetized rats. DESIGN: Prospective, randomized animal study. SETTING: Academic research laboratory. SUBJECTS: Adult, male Sprague-Dawley rats. INTERVENTIONS: We assigned 25 male Sprague-Dawley rats into four groups: intraosseous lipid emulsion, intraosseous saline, IV lipid emulsion, and sham/null. Rats were anesthetized with 1.5% isoflurane and 95% oxygen. The left internal carotid artery and both internal jugular veins were cannulated and a flow probe was placed on the right carotid artery. Subsequently, in animals assigned to the intraosseous groups, the greater trochanter of the left proximal femur was exposed and the intraosseous space was cannulated. After surgical recovery, bupivacaine (10 mg/kg) was injected IV over 20 seconds followed 10 seconds later by treatment with one of the following: intraosseous lipid-emulsion (10 mL/kg over 180 s), intraosseous saline (10 mL/kg over 180 s), IV lipid-emulsion (10 mL/kg over 90 s), or no treatment (sham/null). MEASUREMENTS AND MAIN RESULTS: Electrocardiogram, aortic blood pressure, and carotid blood flow were recorded continuously. Rats treated with intraosseous lipid emulsion experienced a significantly faster recovery of hemodynamic variables (return of 50% flow; median [CI]: 160 s [105-263 s]) than did rats treated with saline (471 s [283-611 s]; p < 0.05) or animals with no treatment (415 s [340-539 s], p < 0.05), but at a similar rate to animals treated with IV lipid emulsion (176 s [152-217 s], p = not significant). All groups experienced persistent negative chronotropic effects. A compensatory increase in systemic arterial pressure was observed in rats treated with lipid emulsion. CONCLUSION: These proof-of-principle data indicate that intraosseous infusion of lipid emulsion rapidly reverses bupivacaine-induced cardiac toxicity in rats. Further studies are warranted to optimize this novel route of lipid emulsion injection in emergency situations when intravascular access is not secured.
Assuntos
Anestésicos Locais/toxicidade , Bupivacaína/toxicidade , Tratamento de Emergência , Emulsões/administração & dosagem , Cardiopatias/induzido quimicamente , Cardiopatias/terapia , Lipídeos/administração & dosagem , Animais , Infusões Intraósseas , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Recent publications have questioned the validity of the "lipid sink" theory of lipid resuscitation while others have identified sink-independent effects and posed alternative mechanisms such as hemodilution. To address these issues, the authors tested the dose-dependent response to intravenous lipid emulsion during reversal of bupivacaine-induced cardiovascular toxicity in vivo. Subsequently, the authors modeled the relative contribution of volume resuscitation, drug sequestration, inotropy and combined drug sequestration, and inotropy to this response with the use of an in silico model. METHODS: Rats were surgically prepared to monitor cardiovascular metrics and deliver drugs. After catheterization and instrumentation, animals received a nonlethal dose of bupivacaine to produce transient cardiovascular toxicity, then were randomized to receive one of the four treatments: 30% intravenous lipid emulsion, 20% intravenous lipid emulsion, intravenous saline, or no treatment (n = 7 per condition; 28 total animals). Recovery responses were compared with the predictions of a pharmacokinetic-pharmacodynamic model parameterized using previously published laboratory data. RESULTS: Rats treated with lipid emulsions recovered faster than did rats treated with saline or no treatment. Intravenous lipid emulsion of 30% elicited the fastest hemodynamic recovery followed in order by 20% intravenous lipid emulsion, saline, and no treatment. An increase in arterial blood pressure underlay the recovery in both lipid emulsion-treated groups. Heart rates remained depressed in all four groups throughout the observation period. Model predictions mirrored the experimental recovery, and the model that combined volume, sequestration, and inotropy predicted in vivo results most accurately. CONCLUSION: Intravenous lipid emulsion accelerates cardiovascular recovery from bupivacaine toxicity in a dose-dependent manner, which is driven by a cardiotonic response that complements the previously reported sequestration effect.
Assuntos
Bupivacaína/toxicidade , Cardiotônicos/uso terapêutico , Emulsões Gordurosas Intravenosas/uso terapêutico , Parada Cardíaca/induzido quimicamente , Parada Cardíaca/terapia , Ressuscitação/métodos , Anestésicos Locais/toxicidade , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Coração/efeitos dos fármacos , Coração/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Cloreto de Sódio/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: Diagnosing alpha-1 antitrypsin deficiency (A1ATD) involves two-step laboratory testing, determination of serum alpha-1 antitrypsin (A1AT) level and phenotyping if A1AT < 100 mg/dL. Whether these guidelines are effectuated in clinical practice is uncertain. To begin to address this issue, we determined whether A1AT phenotyping is performed in patients with serum A1AT 57 - 99 mg/dL at our institution. Methods: We reviewed the medical records of patients seen at Jesse Brown Veterans Affairs Medical Center from January 2019 to October 2022 with serum A1AT between 57 and 99 mg/dL. In each case, pertinent demographic, clinical, and pulmonary function tests data were extracted. Data were presented as means and standard deviation (SD) where appropriate. The Student's t-test was used for statistical analysis. P < 0.05 was considered statistically significant. Results: Thirty patients (90% males; 60 ± 18 years) with serum A1ATD < 100 mg/mL were identified. Fourteen were African Americans, four Hispanics, and 12 non-Hispanic Whites. The majority were current or ex-smokers. Fourteen (47%) patients had lung disease, 14 (47%) liver disease and one had concomitant lung and liver diseases. Mean ± SD forced expiratory volume in 1 s (FEV1) and lung diffusing capacity were 2.57 ± 1.41 L (67±19% predicated) and 18.7 ± 10 mL/min/mm Hg (64±28% predicted), respectively. Only 13 patients (43%) underwent phenotype testing (seven African Americans, five Whites, and one Hispanic). Six patients had MZ phenotype, four MS, and three SZ. One patient died from acute respiratory failure during the study period. Conclusions: Phenotyping of patients with serum A1AT 57 - 99 mg/dL at our institution is inadequate. Accordingly, regular continuous medical educational programs on A1AT phenotyping targeting healthcare providers are warranted.
RESUMO
Administration of high-dose vitamin K1 (VK1) overcomes coagulopathy and bleeding elicited by acute poisoning with long-acting anticoagulant rodenticides (LAARs). However, long-term (months) treatment is required due to long LAAR biological half-lives that may lead to poor compliance and recurrent coagulopathy. The half-lives of LAARs are extended by slow metabolism, and similar to warfarin, are thought to undergo enterohepatic recirculation. We now show that treatment with the bile acid sequestrant cholestyramine (CSA) administered concomitantly with VK1 decreases plasma LAAR levels and increases LAAR fecal excretion. Daily CSA treatment for 14 days did not reduce plasma VK1 levels, or increase prothrombin time. Collectively, these data show that CSA accelerates LAAR clearance from rabbits without adverse effects on VK1 anticoagulation, and could provide an additional therapeutic option for treatment of LAAR poisoning.
Assuntos
Anticoagulantes , Coagulação Sanguínea , Resina de Colestiramina , Fezes , Rodenticidas , Vitamina K 1 , Animais , Coelhos , Rodenticidas/farmacocinética , Rodenticidas/sangue , Anticoagulantes/administração & dosagem , Anticoagulantes/farmacocinética , Vitamina K 1/sangue , Vitamina K 1/administração & dosagem , Coagulação Sanguínea/efeitos dos fármacos , Masculino , Fezes/química , Meia-Vida , Tempo de Protrombina , Taxa de Depuração MetabólicaRESUMO
Rationale: Hospital readmission within 30 days poses challenges for healthcare providers, policymakers, and patients because of its impact on care quality, costs, and outcomes. Patients with interstitial lung disease (ILD) are particularly affected by readmission, which is associated with increased morbidity and mortality and reduced quality of life. Because small sample sizes have hindered previous studies, this study seeks to address this gap in knowledge by examining a large-scale dataset. Objective: To determine the rate and probability of 30-day all-cause readmission and secondary outcomes in patients with coronavirus disease (COVID-19) or ILD admitted to the hospital. Methods: This study is a nested cohort study that used the PearlDiver patient records database. Adult patients (age ⩾18 yr) who were admitted to hospitals in 28 states in the United States with COVID-19 or ILD diagnoses were included. We defined and analyzed two separate cohorts in this study. The first cohort consisted of patients with COVID-19 and was later divided into two groups with or without a history of ILD. The second cohort consisted of patients with ILD and was later divided into groups with COVID-19 or with a non-COVID-19 pneumonia diagnosis at admission. We also studied two other subcohorts of patients with and without idiopathic pulmonary fibrosis within the second cohort. Propensity score matching was employed to match confounders between groups. The Kaplan-Meier log rank test was applied to compare the probabilities of outcomes. Results: We assessed the data of 2,286,775 patients with COVID-19 and 118,892 patients with ILD. We found that patients with COVID-19 with preexisting ILD had an odds ratio of 1.6 for 30-day all-cause readmission. Similarly, an odds ratio of 2.42 in readmission rates was observed among hospitalized individuals with ILD who contracted COVID-19 compared with those who were hospitalized for non-COVID-19 pneumonia. Our study also found a significantly higher probability of intensive care admission among patients in both cohorts. Conclusions: Patients with ILD face heightened rates of hospital readmissions, particularly when ILD is combined with COVID-19, resulting in adverse outcomes such as decreased quality of life and increased healthcare expenses. It is imperative to prioritize preventive measures against COVID-19 and establish effective postdischarge care strategies for patients with ILD.
Assuntos
COVID-19 , Doenças Pulmonares Intersticiais , Pneumonia , Adulto , Humanos , Estados Unidos/epidemiologia , Readmissão do Paciente , Estudos de Coortes , Qualidade de Vida , Assistência ao Convalescente , COVID-19/epidemiologia , COVID-19/complicações , Alta do Paciente , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/terapia , Doenças Pulmonares Intersticiais/complicações , Pneumonia/complicaçõesRESUMO
The COVID-19 pandemic has resulted in a growing number of patients experiencing persistent symptoms and physiological changes after recovering from acute SARS-CoV-2 infection, known as Long COVID. Long COVID is characterized by recurring symptoms and inflammation across multiple organ systems. Diagnosis can be challenging, influenced by factors like demographics, comorbidities, and immune responses. Long COVID impacts various organ systems and can have neuropsychological effects. Health disparities, particularly related to race, contribute to a higher burden of infection and ongoing symptoms in minority populations. Managing Long COVID entails addressing a spectrum of symptoms that encompass physical, cognitive, and psychological aspects. The recovery period for patients with Long COVID can vary significantly, influenced by factors like the severity of the disease, hospitalization, comorbidities, and age. Currently, there are no universally effective treatments, although certain interventions show promise, necessitating further research. Self-management and rehabilitation programs can provide relief, but more research is needed to establish their effectiveness. Preventive measures such as vaccination and the use of antiviral medications and metformin. It is imperative to conduct further research to develop evidence-based guidelines and gain a better understanding of the long-term implications of COVID-19. Long COVID could have substantial economic impact on the labor market, productivity, healthcare expenditures, and overall economic growth. To address the challenges patients with long-term complications face, there is a focus on strategies like promoting telework and flexible work arrangements to accommodate diverse symptoms, particularly chronic fatigue and other Long COVID effects. In conclusion, this review emphasizes the multifaceted complexity of Long COVID and the ongoing need to address its potential long-term health and economic impacts.
Assuntos
COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , COVID-19/epidemiologia , Pandemias , SARS-CoV-2 , Desigualdades de SaúdeRESUMO
BACKGROUND: In the first months of the pandemic, prior to the introduction of proven-effective treatments, 15-37% of patients hospitalized with COVID-19 were discharged on home oxygen. After proven-effective treatments for acute COVID-19 were established by evidence-based guidelines, little remains known about home oxygen requirements following hospitalization for COVID-19. METHODS: This was a retrospective, multi-center cohort study of subjects hospitalized for COVID-19 between October 2020-September 2021 at 3 academic health centers. Information was abstracted from electronic health records at the index hospitalization and for 60 d after discharge. The World Health Organization COVID-19 Clinical Progression Scale score was used to identify patients with severe COVID-19. RESULTS: Of 517 subjects (mean age 58 y, 47% female, 42% Black, 36% Hispanic, 22% with severe COVID-19), 81% were treated with systemic corticosteroids, 61% with remdesivir, and 2.5% with tocilizumab. About one quarter of subjects were discharged on home oxygen (26% [95% CI 22-29]). Older age (adjusted odds ratio [aOR] 1.02 per 5 y [95% CI 1.02-1.02]), higher body mass index (aOR 1.02 per kg/m2 [1.00-1.04]), diabetes (yes vs no, aOR 1.73 [1.46-2.02]), severe COVID-19 (vs moderate, aOR 3.19 [2.19-4.64]), and treatment with systemic corticosteroids (yes vs no, aOR 30.63 [4.51-208.17]) were associated with an increased odds of discharge on home oxygen. Comorbid hypertension (yes vs no, aOR 0.71 [0.66-0.77) was associated with a decreased odds of home oxygen. Within 60 d of hospital discharge, 50% had documentation of pulse oximetry; in this group, home oxygen was discontinued in 46%. CONCLUSIONS: About one in 4 subjects were prescribed home oxygen after hospitalization for COVID-19, even after guidelines established proven-effective treatments for acute illness. Evidence-based strategies to reduce the requirement for home oxygen in patients hospitalized for COVID-19 are needed.