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Glioblastoma (GBM) is a lethal astrocyte-derived tumor that is currently treated with a multi-modal approach of surgical resection, radiotherapy, and temozolomide-based chemotherapy. Alternatives to current therapies are urgently needed as its prognosis remains poor. Anthracyclines are a class of compounds that show great potential as GBM chemotherapeutic agents and are widely used to treat solid tumors outside the central nervous system. Here we investigate the cytotoxic effects of doxorubicin and other anthracyclines on GL261 glioma tumor cells in anticipation of novel anthracycline-based CNS therapies. Three methods were used to quantify dose-dependent effects of anthracyclines on adherent GL261 tumor cells, a murine cell-based model of GBM. MTT assays quantified anthracycline effects on cell viability, comet assays examined doxorubicin genotoxicity, and flow cytometry with Annexin V/PI staining characterized doxorubicin-induced apoptosis and necrosis. Dose-dependent reductions in GL261 cell viability were found in cells treated with doxorubicin (EC50 = 4.9 µM), epirubicin (EC50 = 5.9 µM), and idarubicin (EC50 = 4.4 µM). Comet assays showed DNA damage following doxorubicin treatments, peaking at concentrations of 1.0 µM and declining after 25 µM. Lastly, flow cytometric analysis of doxorubicin-treated cells showed dose-dependent induction of apoptosis (EC50 = 5.2 µM). Together, these results characterized the cytotoxic effects of anthracyclines on GL261 glioma cells. We found dose-dependent apoptotic induction; however at high concentrations we find that cell death is likely necrotic. Our results support the continued exploration of anthracyclines as compounds with significant potential for improved GBM treatments.
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Antibióticos Antineoplásicos/farmacologia , Citotoxinas/farmacologia , Doxorrubicina/farmacologia , Epirubicina/farmacologia , Idarubicina/farmacologia , Neuroglia/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Fragmentação do DNA/efeitos dos fármacos , Relação Dose-Resposta a Droga , Glioma/tratamento farmacológico , Humanos , Camundongos , Modelos Biológicos , Neuroglia/metabolismo , Neuroglia/patologiaRESUMO
Traditional socio-ecological models consider that folivorous primates experience limited feeding competition due to the low quality, high abundance, and even distribution of leaves. Evidence from several folivorous species that experience similar constraints to frugivores does not support this hypothesis. The sympatric lemur genera Avahi (Indriidae) and Lepilemur (Lepilemuridae) are good models to understand how food availability constrains folivores since they are both nocturnal, folivorous, and have a comparable body mass. Here we investigate how two nocturnal folivorous primates, Avahi meridionalis and Lepilemur fleuretae, living in the lowland rain forest of Tsitongambarika, South-East Madagascar, partition their dietary niche and are influenced by seasonality of young leaves. To account for food availability, we collected annual phenological data on 769 trees from 200 species. We also collected behavioural data on 5 individuals per lemur species from August 2015 to July 2016 via continuous focal sampling. We found the phenological profile to be seasonal with peaks of leaf flushing, flowering, and fruiting occurring in the austral summer. The two species showed limited dietary overlap (37% rich period, 6% lean period), and A. meridionalis showed higher feeding time and longer daily distances travelled during the rich period. Lepilemur fleuretae showed a dietary shift during the lean period, relying more on mature leaves (73.3% during the lean period, 13.5% during the rich period) but maintaining similar activity levels between seasons. The time spent feeding on food items by A. meridionalis was positively correlated with the nitrogen content and negatively correlated with polyphenols during the rich period. We highlighted a clear effect of the seasonality of young leaves on the diet, nutritional content, activity patterns, and daily distances travelled by two folivorous species, which can be linked to nutrient balancing and time-minimising versus energy-maximising strategies.
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Dieta/veterinária , Folhas de Planta , Strepsirhini/fisiologia , Animais , Ecossistema , Feminino , Madagáscar , Masculino , Folhas de Planta/crescimento & desenvolvimento , Estações do Ano , Especificidade da EspécieRESUMO
Objective: To review the clinical effects of nebulized heparin and N-acetylcysteine (NAC) in patients with smoke inhalation injury (IHI) and provide recommendations for use. Data Sources: A search of PubMed, MEDLINE, and Scopus databases was completed from database inception through April 15, 2020, using terms: heparin, acetylcysteine, smoke inhalation injury, and burn injury. Study Selection and Data Extraction: All studies pertaining to efficacy and safety of nebulized heparin and/or NAC for IHI in adult patients were evaluated. Reference lists were reviewed for additional publications. Nonhuman studies, non-English, and case report publications were excluded. Data Synthesis: Eight studies were included. Four demonstrated positive outcomes, 3 demonstrated no benefit or possible harm, and 1 assessed safety. Supporting trials treated patients within 48 hours of injury with 10 000 units of nebulized heparin with NAC for 7 days or until extubation. Two trials with negative findings treated patients within 72 hours, or unspecified, with 5000 units of nebulized heparin with NAC for 7 days, while the third used 25 000 units within 36 hours but was grossly underpowered for analysis. Clinical findings include reduced duration of mechanical ventilation and improved lung function with possible increase risk of pneumonia and no evidence of increased bleeding risk. Conclusions: Nebulized heparin may improve oxygenation and reduce duration of mechanical ventilation in IHI. If nebulized heparin is used, 10 000 units every 4 hours alternating with NAC and albuterol at 4-hour intervals is recommended. Sterile technique should be emphasized. Monitoring for bronchospasm or new-onset pneumonia should be considered.
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INTRODUCTION: Low-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited. OBJECTIVES: The primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct oral anticoagulant for treatment of cancer-associated thrombosis. Secondary objectives were to determine the rates of clinically relevant-non-major bleeding and all-cause mortality. PATIENTS/METHODS: This is a retrospective cohort study including adults with cancer-associated thrombosis treated with low-molecular-weight heparin or direct oral anticoagulant between 2010 and 2016 at the Ohio State University. Medical records were reviewed for 6 months after initiation of anticoagulation or until the occurrence of recurrent cancer-associated thrombosis, major bleeding, cessation of anticoagulation of interest, or death, whichever occurred first. RESULTS: Four hundred and eighty patients were included (290 low-molecular-weight heparin and 190 direct oral anticoagulant). Patients treated with direct oral anticoagulant were found to carry "lower risk" features including cancer with lower VTE risk and lower rate of metastatic disease. After adjustment for baseline differences, there was no significant difference in the rate of recurrent cancer-associated thrombosis (7.2% low-molecular-weight heparin vs 6.3% direct oral anticoagulant, p = 0.71) or major bleeding (7.6% low-molecular-weight heparin vs 2.6% direct oral anticoagulant, p = 0.08). CONCLUSIONS: Our study demonstrates that in a select population of cancer patients with VTE, direct oral anticoagulant use can be as effective and safe compared to the standard therapy with low-molecular-weight heparin.
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Anticoagulantes/uso terapêutico , Heparina de Baixo Peso Molecular/uso terapêutico , Neoplasias/complicações , Tromboembolia Venosa/tratamento farmacológico , Administração Oral , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Mobile device use has become almost ubiquitous in daily life and therefore includes use by doctors in clinical settings. There has been little study as to the patterns of use and impact this has on doctors in the workplace and how negatively or positively it impacts at the point of care. AIM: To explore how doctors use mobile devices in the clinical setting and understand drivers for use. METHODS: A mixed methods study was used with doctors in a paediatric and adult teaching hospital in 2013. A paper-based survey examined mobile device usage data by doctors in the clinical setting. Focus groups explored doctors' reasons for using or refraining from using mobile devices in the clinical setting, and their attitudes about others' use. RESULTS: The survey, completed by 109 doctors, showed that 91% owned a smartphone and 88% used their mobile devices frequently in the clinical setting. Trainees were more likely than consultants to use their mobile devices for learning and accessing information related to patient care, as well as for personal communication unrelated to work. Focus group data highlighted a range of factors that influenced doctors to use personal mobile devices in the clinical setting, including convenience for medical photography, and factors that limited use. Distraction in the clinical setting due to use of mobile devices was a key issue. Personal experience and confidence in using mobile devices affected their use, and was guided by role modelling and expectations within a medical team. CONCLUSION: Doctors use mobile devices to enhance efficiency in the workplace. In the current environment, doctors are making their own decisions based on balancing the risks and benefits of using mobile devices in the clinical setting. There is a need for guidelines around acceptable and ethical use that is patient-centred and that respects patient privacy.
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Telefone Celular/estatística & dados numéricos , Competência Clínica/normas , Fidelidade a Diretrizes , Aplicativos Móveis/estatística & dados numéricos , Assistência Centrada no Paciente/normas , Médicos , Local de Trabalho , Adulto , Idoso , Atitude do Pessoal de Saúde , Austrália , Telefone Celular/ética , Comunicação , Feminino , Grupos Focais , Fidelidade a Diretrizes/ética , Humanos , Comportamento de Busca de Informação , Masculino , Pessoa de Meia-Idade , Aplicativos Móveis/ética , Preferência do Paciente , Guias de Prática Clínica como Assunto , Adulto JovemRESUMO
BACKGROUND: Medication reconciliation has been shown to reduce medication-related errors in hospitalized patients, but the impact of pharmacy-led medication reconciliation in the intensive care unit (ICU) has not been extensively studied. METHODS: This was a retrospective chart review of patients with a pharmacy-led medication reconciliation on admission to an ICU between January 1st and March 31st, 2018. Pharmacy-led medication reconciliations were completed by pharmacists, pharmacy residents, and pharmacy students. The objective of this study was to describe medication discrepancies identified by pharmacy-led medication reconciliation and to evaluate the interventions following. RESULTS: A total of 288 patients were screened and 247 met inclusion criteria. There were 1148 medication discrepancies identified resulting in an average of 4.65 discrepancies per patient. Medication addition (54.25%) and medication deletion (45.75%) were most common. Within 24 hours of medication reconciliation, 214 interventions were made to active orders. No differences were observed between discrepancies identified and type of pharmacy staff completing the medication reconciliation. CONCLUSIONS: This study identified a high rate of medication discrepancies on admission to the ICU. Furthermore, it describes the types of pharmacist interventions following pharmacy-led medication reconciliation. This process may be impactful to incorporate as a standard practice in ICUs and warrants further investigation into value, cost, and pharmacist workflow.
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OBJECTIVE: The present study aimed to assess the prevalence and predictors of anxiety and depression in Australian chronic hepatitis C (CHC) outpatients. METHOD: Hospital Anxiety and Depression Scale scores at referral and other patient data was analysed for 395 CHC outpatients attending the Royal Adelaide Hospital liver clinic from 2006 to 2010. RESULTS: Results revealed probable prevalence rates of 41% for anxiety and 27% for depression. CHC patients had rates of anxiety and depression 1.2 and 2.4 times higher than community norms, respectively. Younger patients were found to experience increased anxiety, while married patients or those in a de facto relationship experienced decreased anxiety and depression. CONCLUSION: Regular psychiatric screening, and subsequent referral for mental health treatment, where necessary, is recommended for Australian CHC patients. Younger patients or those lacking social supports may be at increased risk. Research is needed to develop and evaluate psychological interventions.
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Ansiedade/epidemiologia , Depressão/epidemiologia , Hepatite C Crônica/epidemiologia , Pacientes Ambulatoriais/psicologia , Adulto , Ansiedade/complicações , Austrália/epidemiologia , Depressão/complicações , Feminino , Hepatite C Crônica/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Prevalência , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Fatores de RiscoRESUMO
We describe a case of a 58-year-old male who presented to the emergency room with symptoms related to an appendicitis. A computed tomography scan with contrast confirmed the diagnosis of acute appendicitis but also revealed a mass medially in the base of the inferior lobe of the right lung. The mass measured 6.7 cm AP × 3.7 cm transverse. It had multiple lobulations and the anterior aspect was of very low density, possibly representing accumulated mucoid material. The mass had an arterial connection from the descending thoracic aorta and a venous drainage into the right pulmonary vein, classical features of intralobar pulmonary sequestration. The physical exam was unremarkable, and the patient had no history of pulmonary symptoms. This case helps increase awareness of intralobar pulmonary sequestration, a rare condition that may be asymptomatic.