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INTRODUCTION: Women and underrepresented groups in medicine hold few academic leadership positions in the field of hematology/oncology. In this study, we assessed gender and race/ethnicity representation in editorial board positions in hematology/oncology journals. MATERIALS AND METHODS: Editorial leadership board members from 60 major journals in hematology and oncology were reviewed; 54 journals were included in the final analysis. Gender and race/ethnicity were determined based on publicly available data for Editor-in-Chief (EiC) and Second-in-Command (SiC) (including deputy, senior, or associate editors). Descriptive statistics and chi-squared were estimated. In the second phase of the study, editors were emailed a 4-item survey to self-identify their demographics. RESULTS: Out of 793 editorial board members, 72.6% were men and 27.4% were women. Editorial leadership were non-Hispanic white (71.1%) with Asian editorial board members representing the second largest majority at 22.5%. Women comprised only 15.9% of the EiC positions (90% White and 10% Asian). Women were about half as likely to be in the EiC position compared with men [pOR 0.47 (95% CI, 0.23-0.95, P = .03)]. Women represented 28.3% of SiC editorial positions. Surgical oncology had the lowest female representation at 2.3%. CONCLUSION: Women and minorities are significantly underrepresented in leadership roles on Editorial Boards in hematology/oncology journals. Importantly, the representation of minority women physicians in EiC positions is at an inexorable zero.
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Hematologia , Médicas , Masculino , Humanos , Feminino , Etnicidade , OncologiaRESUMO
OBJECTIVES: Routine gastric aspirate (RGA) monitoring is a common yet controversial practice intended for early identification of gastrointestinal pathology in infants receiving gavage feeds. Our objectives were to evaluate the association of ceasing RGA monitoring on the incidence of necrotizing enterocolitis (NEC) as well as nutritional outcomes in a large population of very low birth weight (VLBW) and very preterm neonates. METHODS: Retrospective record review of neonates born ≤32 weeks and/or VLBW from 2 cohorts: (1) during pre-feed RGA monitoring (September 2015 to June 2018) and (2) after cessation of RGA ("non-RGA") monitoring (July 2018 to December 2020). We compared incidence of NEC, time-to-full enteral feeds, central line duration, and duration of parenteral nutrition (PN) in bivariate and multivariable models accounting for changes in feeding protocols over time. RESULTS: We identified 617 subjects, 53% in the RGA monitoring cohort (n = 327) and 47% in non-RGA cohort (n = 290). The non-RGA cohort had feeds initiated earlier ( P < 0.0001), achieved full enteral feeds more rapidly ( P < 0.0001), received a shorter duration of PN ( P = 0.0003), and had shorter central access duration ( P < 0.0001) without increasing NEC risk. In fact, the non-RGA cohort had a lower incidence of NEC ( P = 0.0345) compared to the RGA cohort. Even after adjusting for changes in feeding protocols over time in a multivariable model, the RGA cohort had significantly higher odds of NEC. CONCLUSIONS: Pre-feed RGA monitoring in the absence of concerning clinical exam findings is not indicated for neonates receiving gavage feeds as it does not improve NEC incidence but instead may delay important nutritional outcomes such as feed initiation and central line removal.
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Enterocolite Necrosante , Doenças do Prematuro , Recém-Nascido , Humanos , Recém-Nascido Prematuro , Estudos Retrospectivos , Recém-Nascido de muito Baixo Peso , Doenças do Prematuro/etiologia , Fatores de Tempo , Enterocolite Necrosante/diagnóstico , Enterocolite Necrosante/epidemiologia , Enterocolite Necrosante/etiologia , Peso ao NascerRESUMO
This is an invited editorial on radiologist burnout, its presenting manifestations, toll on patient care and systems-based practice, and suggested remedies to mitigate stress and exhaustion.
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Esgotamento Profissional , Esgotamento Profissional/prevenção & controle , Humanos , Radiologistas , Inquéritos e QuestionáriosRESUMO
Extracorporeal membrane oxygenation (ECMO)-related hemolysis is common with reported incidence of 5%-18%. Plasma free hemoglobin (PFH) levels are used as a marker for hemolysis and elevated PFH is associated with acute kidney injury (AKI). Limited literature exists regarding treatment of severe hemolysis and clearance of PFH. We report 8-year-old male child on VA ECMO with severe hemolysis (PFH 895 mg/dL) and worsening AKI showing significant improvement in PFH after single volume exchange plasmapheresis with Fresh Frozen Plasma (FFP) performed in tandem via ECMO circuit.
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Injúria Renal Aguda , Oxigenação por Membrana Extracorpórea , Criança , Hemoglobinas/análise , Hemólise , Humanos , Masculino , Troca Plasmática , Plasmaferese , Estudos RetrospectivosRESUMO
BACKGROUND: The proportion of women in the field of hematology and oncology (H&O) has increased over recent decades, but the representation of women in leadership positions remains poor. In an effort to close the gender gap in academia, it is important to report on such inequities in hopes to close these gaps and improve career development. MATERIALS AND METHODS: We conducted a retrospective, observational study of published award recipients from 1994 to 2019 from the seven major H&O societies in the world. Gender was determined based on publicly available data. The χ2 and Cochran-Armitage tests were used for data analysis. RESULTS: Of the 1,642 awardees over the past 26 years, 915 met inclusion criteria. Award recipients were overwhelmingly men (77.9%) and non-Hispanic White (84.7%). Women awardees received 30.3% of the humanistic and education-related awards, whereas only receiving 16.0% of basic science awards (p < .01). Women represent 35.6% of all hematologists and oncologists but only received 24.0% of awards given to these physicians (p = .004). Black, Hispanic, and Asian awardees represented 3.7%, 3.3%, and 6.8% of the total awardees, respectively. CONCLUSION: From 1994 to 2019, women were less likely to receive recognition awards from the seven major H&O societies studied compared with men. We also observed a considerably low proportion of minority awardees across all oncology subspecialties. Further studies examining how selection criteria favor either gender would be warranted in order to achieve equal representation in academic awards. IMPLICATIONS FOR PRACTICE: In this study, women and minority groups were found to be underrepresented amongst award recipients. Significant disparities were seen in disciplines that have been historically male predominant, such as basic sciences. As awards on an international level enhance academic resumes and assist with career advancement, it is important that awards are being given in an equitable manner. First steps to promote diversity and inclusion in academic medicine is reporting of gender and racial disparities in various areas of academia.
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Distinções e Prêmios , Hematologia , Médicos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Sociedades MédicasRESUMO
17ß-estradiol (E2)-containing hormone therapy is a safe, effective way to alleviate unwanted menopause symptoms. Preclinical research has focused upon the role of E2 in learning and memory using a surgically menopausal rodent model whereby the ovaries are removed. Given that most women retain their reproductive tract and undergo a natural menopause transition, it is necessary to understand how exogenous E2 impacts a structurally intact, but follicle-deplete, system. In the current study, 8 month old female rats were administered the ovatoxin 4-vinylcyclohexene diepoxide (VCD), which accelerates ovarian follicular depletion, to model the human menopause transition. After follicular depletion, at 11 months old, rats were administered Vehicle or tonic E2 treatment for 12 days prior to behavioral evaluation on spatial working and reference memory tasks. Results demonstrated that E2 had both enhancing and impairing effects on taxed working memory depending upon the learning or retention phases of the water radial-arm maze, with no impact on reference memory. Relationships between memory scores and circulating estrogen levels were specific to follicle-depleted rats without E2 treatment. Collectively, findings demonstrate the complexity of E2 administration in a follicle-depleted background, with cognitive effects specific to working memory; furthermore, E2 administration altered circulating hormonal milieu and relationships between hormone profiles and memory. In sum, menopausal etiology impacts the parameters of E2 effects on cognition, complementing prior work with other estrogen compounds. Deciphering estrogenic actions in a system wherein the reproductive tract remains intact with follicle-depleted ovaries, thus modeling the majority or menopausal women, is critical for translational perspectives.
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Envelhecimento/efeitos dos fármacos , Estradiol/farmacologia , Memória/efeitos dos fármacos , Reserva Ovariana/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Envelhecimento/fisiologia , Envelhecimento/psicologia , Animais , Cognição/efeitos dos fármacos , Cicloexenos , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória de Curto Prazo/efeitos dos fármacos , Menopausa/efeitos dos fármacos , Menopausa/psicologia , Modelos Animais , Folículo Ovariano/citologia , Folículo Ovariano/efeitos dos fármacos , Ovário/citologia , Ovário/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Compostos de VinilaRESUMO
BACKGROUND: Racial disparities have been reported in liver transplantation and chronic hepatitis C treatment outcomes. Determining causes of these disparities is important given the racially diverse American population and the economic burden associated with chronic liver disease. METHODS: A retrospective study was performed among 463 patients diagnosed with cirrhosis admitted from (January 1, 2013 to January 1, 2018) to a tertiary care academic medical center. Patients were identified based on the International Classification of Diseases (ICD-10) for cirrhosis or its complications. Demographic information, laboratory data, medical comorbidities, insurance and adherence to cirrhosis quality care indicators were recorded to determine their relationship to readmission rates and other healthcare outcomes. RESULTS: A total of 463 individual patients with cirrhosis were identified including Whites (n = 241), Hispanics (n = 106), Blacks (n = 50), Asian and Pacific Islander Americans (API, n = 27) and Other (n = 39). A significantly higher proportion of Blacks had Medicaid insurance compared to Whites (40% versus 20%, p = 0.0002) and Blacks had lower median income than Whites ($45,710 versus $54,844, p = 0.01). All groups received high quality cirrhosis care. Regarding healthcare outcomes, Black patients had the highest mean total hospital admissions (6.1 ± 6.3, p = 0.01) and the highest mean number of 30-day re-admissions (2.1 ± 3.7, p = 0.05) compared to all other racial groups. Multivariable proportional odds regression analysis showed that race was a statistically significant predictor of 90-day readmission (p = 0.03). CONCLUSIONS: Black Americans hospitalized for complications of cirrhosis may experience significant disparities in healthcare outcomes compared to Whites despite high quality cirrhosis care. Socioeconomic factors may contribute to these disparities.
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Negro ou Afro-Americano , Disparidades em Assistência à Saúde , Hispânico ou Latino , Humanos , Cirrose Hepática , Estudos Retrospectivos , Estados Unidos/epidemiologia , População BrancaRESUMO
Multiple-choice examinations (MCEs) are commonly used to evaluate nursing students. Nurse educators require support to develop questions and engage in postexam analysis to ensure reliable assessment of student learning. We surveyed nurse educators and conducted focus groups to investigate current writing practices associated with MCEs. Using appreciative inquiry, participants proposed ideals to strengthen MCE practice: guidelines and expectations for faculty, faculty-developed test banks, team development, and an assessment blueprint at the curriculum level. Faculty supports are necessary to strengthen current MCE practices and best utilize the skills of educators.
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Prática do Docente de Enfermagem , Estudantes de Enfermagem , Currículo , Docentes de Enfermagem , Humanos , Inquéritos e QuestionáriosRESUMO
Gardner's syndrome (GS), a variant of familial adenomatous polyposis (FAP), remains a life-threatening condition of significant dental relevance. Clinicians can play an important role in the identification of this condition as the dental manifestations often precede the development of intestinal polyposis. This article describes a clinical case in which identification of the dental features of GS during routine orthodontic assessment resulted in the early diagnosis of this condition, which was previously unrecognised in a young female patient.
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Síndrome de Gardner/diagnóstico , Polipose Adenomatosa do Colo , Criança , Feminino , HumanosRESUMO
RATIONALE: Intensive care unit (ICU) delirium is associated with ventilator, ICU, and hospital days; discharge functional status; and mortality. Whether rapidly reversible, sedation-related delirium (delirium that abates shortly after sedative interruption) occurs with the same frequency and portends the same prognosis as persistent delirium (delirium that persists despite a short period of sedative interruption) is unknown. OBJECTIVES: To compare rapidly reversible, sedation-related delirium and persistent delirium. METHODS: This was a prospective cohort study of 102 adult, intubated medical ICU subjects in a tertiary care teaching hospital. Confusion Assessment Method for the ICU evaluation was performed before and after daily interruption of continuous sedation (DIS). Investigators were blinded to each other's assessments and as to whether evaluations were before or after DIS. The primary outcome was proportion of days with no delirium versus rapidly reversible, sedation-related delirium versus persistent delirium. Secondary outcomes were ventilator, ICU, and hospital days; discharge disposition; and 1-year mortality. MEASUREMENTS AND MAIN RESULTS: The median proportion of ICU days with delirium was 0.57 before versus 0.50 after DIS (P < 0.001). The Confusion Assessment Method for the ICU indicated patients are 10.5 times more likely to have delirium before DIS versus after (P < 0.001). Rapidly reversible, sedation-related delirium showed fewer ventilator (P < 0.001), ICU (P = 0.001), and hospital days (P < 0.001) than persistent delirium. Subjects with no delirium and rapidly reversible, sedation-related delirium were more likely to be discharged home (P < 0.001). Patients with persistent delirium had increased 1-year mortality versus those with no delirium and rapidly reversible, sedation-related delirium (P < 0.001). CONCLUSIONS: Rapidly reversible, sedation-related delirium does not signify the same poor prognosis as persistent delirium. Degree of sedation should be considered in delirium assessments. Coordinating delirium assessments with daily sedative interruption will improve such assessments' ability to prognosticate ICU delirium outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT 00919698).
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Sedação Consciente/efeitos adversos , Delírio/induzido quimicamente , Fentanila/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Unidades de Terapia Intensiva , Propofol/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Sedação Consciente/métodos , Cuidados Críticos/métodos , Delírio/diagnóstico , Delírio/mortalidade , Delírio/terapia , Feminino , Seguimentos , Humanos , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Respiração Artificial/estatística & dados numéricos , Método Simples-Cego , Adulto JovemRESUMO
Dehydrins protect plant proteins and membranes from damage during drought and cold. Vitis riparia K2 is a 48-residue protein that can protect lactate dehydrogenase from freeze-thaw damage by preventing the aggregation and denaturation of the enzyme. To further elucidate its mechanism, we used a series of V. riparia K2 concatemers (K4, K6, K8, and K10) and natural dehydrins (V. riparia YSK2, 60 kilodalton peach dehydrin [PCA60], barley dehydrin5 [Dhn5], Thellungiella salsuginea dehydrin2 [TsDHN-2], and Opuntia streptacantha dehydrin1 [OpsDHN-1]) to test the effect of the number of K-segments and dehydrin size on their ability to protect lactate dehydrogenase from freeze-thaw damage. The results show that the larger the hydrodynamic radius of the dehydrin, the more effective the cryoprotection. A similar trend is observed with polyethylene glycol, which would suggest that the protection is simply a nonspecific volume exclusion effect that can be manifested by any protein. However, structured proteins of a similar range of sizes did not show the same pattern and level of cryoprotection. Our results suggest that with respect to enzyme protection, dehydrins function primarily as molecular shields and that their intrinsic disorder is required for them to be an effective cryoprotectant. Lastly, we show that the cryoprotection by a dehydrin is not due to any antifreeze protein-like activity, as has been reported previously.
Assuntos
Crioprotetores/farmacologia , Congelamento , Proteínas de Plantas/farmacologia , Proteínas Recombinantes/farmacologia , Proteínas Anticongelantes/química , Proteínas Anticongelantes/farmacologia , Biocatálise/efeitos dos fármacos , Dicroísmo Circular , Crioprotetores/química , Crioprotetores/metabolismo , Cristalização , Hordeum/genética , Hordeum/metabolismo , Gelo , L-Lactato Desidrogenase/metabolismo , Peptídeos/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Prunus/genética , Prunus/metabolismo , Proteínas Recombinantes/metabolismo , Vitis/genética , Vitis/metabolismoRESUMO
The onset of the COVID-19 pandemic led mental health professionals to change the way they engaged with clients, often replacing in-person consultations with virtual ones via telephone or videoconferencing. While studies have investigated the delivery of virtual physical health care, only a handful have investigated the delivery of virtual mental health. These specifically focussed on the outcomes of virtual care whether experiential, practical, or empirical. The transition from in-person to virtual care delivery due to the COVID-19 pandemic has been unexplored. Accordingly, the purpose of the study was to: (1) Explore the experiences of clients who had to transition from an in-person to a virtual provision of mental health care due to the COVID-19 pandemic, and; (2) Explore the nurses' experiences of this technological transition. Using an interpretive phenomenology methodology, semi-structured interviews were conducted with nurses and clients who have experienced the in-person to virtual transition of service delivery at a tertiary mental health hospital in Ontario, Canada. In this article, we focus on the results stemming from our interviews with clients. The themes generated from the analysis of client experiences are 1) the psychosocial impact of the COVID-19 pandemic on clients, (2) mixed feelings of clients towards nursing care delivered via technological means and (3) the role of nurses regarding transitioning of in-person care to technology-mediated care. These findings are relevant as mental health care hospitals are considering how they will deliver services once concerns with the transmission of the COVID-19 virus are resolved.
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COVID-19 , Telessaúde Mental , Enfermagem Psiquiátrica , Humanos , COVID-19/epidemiologia , Atenção à Saúde , Ontário , PandemiasRESUMO
Cancer is the most widely studied disorder in humans, but proper treatment has not yet been developed for it. Conventional therapies, like chemotherapy, radiation therapy, and surgery, have been employed. Such therapies target not only cancerous cells but also harm normal cells. Conventional therapy does not result in specific targeting and hence leads to severe side effects. The main objective of this study is to explore the QDs. QDs are used as nanocarriers for diagnosis and treatment at the same time. They are based on the principle of theranostic approach. QDs can be conjugated with antibodies via various methods that result in targeted therapy. This results in their dual function as a diagnostic and therapeutic tool. Nanotechnology involving such nanocarriers can increase the specificity and reduce the side effects, leaving the normal cells unaffected. This review pays attention to different methods for synthesising QDs. QDs can be obtained using either organic method and synthetic methods. It was found that QDs synthesised naturally are more feasible than the synthetic process. Top or bottom-up approaches have also emerged for the synthesis of QDs. QDs can be conjugated with an antibody via non-covalent and covalent binding. Covalent binding is much more feasible than any other method. Zero-length coupling plays an important role as EDC (1-Ethyl-3-Ethyl dimethylaminopropyl)carbodiimide is a strong crosslinker and is widely used for conjugating molecules. Antibodies work as surface ligands that lead to antigen- antibody interaction, resulting in site-specific targeting and leaving behind the normal cells unaffected. Cellular uptake of the molecule is done by either passive targeting or active targeting. QDs are tiny nanocrystals that are inorganic in nature and vary in size and range. Based on different sizes, they emit light of specific wavelengths. They have their own luminescent and optical properties that lead to the monitoring, imaging, and transport of the therapeutic moiety to a variety of targets in the body. The surface of the QDs is modified to boost their functioning. They act as a tool for diagnosis, imaging, and delivery of therapeutic moieties. For improved therapeutic effects, nanotechnology leads the cellular uptake of nanoparticles via passive targeting or active targeting. It is a crucial platform that not only leads to imaging and diagnosis but also helps to deliver therapeutic moieties to specific sites. Therefore, this review concludes that there are numerous drawbacks to the current cancer treatment options, which ultimately result in treatment failure. Therefore, nanotechnology that involves such a nanocarrier will serve as a tool for overcoming all limitations of the traditional therapeutic approach. This approach helps in reducing the dose of anticancer agents for effective treatment and hence improving the therapeutic index. QDs can not only diagnose a disease but also deliver drugs to the cancerous site.
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Neoplasias , Pontos Quânticos , Nanomedicina Teranóstica , Pontos Quânticos/química , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Nanomedicina Teranóstica/métodos , AnimaisRESUMO
Lung cancer is the leading cause of cancer death for women in multiple countries including the United States. Women are exposed to unique risk factors that remain largely understudied such as indoor pollution, second-hand tobacco exposure, biological differences, gender differences in tolerability and response to therapy in lung cancer, and societal gender roles, that create distinct survivorship needs. Women continue to lack representation in lung cancer clinical trials and are typically treated with data generated from majority male patient study populations, which may be inappropriate to extrapolate and generalize to females. Current lung cancer treatment and screening guidelines do not incorporate sex-specific differences and physicians also often do not account for gender differences when choosing treatments or discussing survivorship needs. To best provide targeted treatment approaches, greater representation of women in lung cancer clinical trials and further research is necessary. Clinicians should understand the unique factors and consequences associated with lung cancer in women; thus, a holistic approach that acknowledges environmental and societal factors is necessary.
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Neoplasias Pulmonares , Humanos , Masculino , Feminino , Estados Unidos/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/etiologia , Fatores de Risco , Fatores Sexuais , PrevisõesRESUMO
OBJECTIVES: Breath-stacking asynchrony during assist-control-mode ventilation may be associated with increased tidal volume and alveolar pressure that could contribute to ventilator-induced lung injury. Methods to reduce breath stacking have not been well studied. The objective of this investigation was to evaluate 1) which interventions were used by managing clinicians to address severe breath stacking; and 2) how effective these measures were. SETTING: Sixteen-bed medical ICU. PATIENTS AND INTERVENTIONS: Physiological study in consecutively admitted patients without severe brain injury, who had severe breath stacking defined as an asynchrony index greater than or equal to 10% of total breaths. During 30 minutes before (baseline) and after any intervention employed by the managing clinician, the ventilator flow, airway pressure, and volume/time waveforms were continuously recorded and analyzed to detect normal and stacked breaths. The initial approach taken was assigned to one of three categories: no intervention, increase of sedation-analgesia, or change of ventilator setting. Nonparametric Wilcoxon-Mann-Whitney tests and multiple regression were used for statistical analysis. Quantitative data are presented as median [25-75]. MAIN RESULTS: Sixty-six of 254 (26%) mechanically ventilated patients exhibited severe breath-stacking asynchrony. A total of 100 30-minute sequences were recorded and analyzed in 30 patients before and after 50 clinical decisions for ongoing management (no intervention, n=8; increasing sedation/analgesia, n=16; ventilator adjustment, n=26). Breath-stacking asynchrony index was 44 [27-87]% at baseline. Compared with baseline, the decrease of asynchrony index was greater after changing the ventilator setting (-99 [-92, -100]%) than after increasing the sedation-analgesia (-41 [-66, 7]%, p<0.001) or deciding to tolerate the asynchrony (4 [-4, 12]%, p<0.001). Pressure-support ventilation and increased inspiratory time were independently associated with the reduction of asynchrony index. CONCLUSIONS: Compared with increasing sedation-analgesia, adapting the ventilator to patient breathing effort reduces breath-stacking asynchrony significantly and often dramatically. These results support an algorithm beginning with ventilator adjustment to rationalize the management of severe breath-stacking asynchrony in ICU patients.
Assuntos
Analgesia/métodos , Sedação Profunda/métodos , Suporte Ventilatório Interativo/métodos , Padrões de Prática Médica , Taxa Respiratória/fisiologia , Lesão Pulmonar Induzida por Ventilação Mecânica/prevenção & controle , Adulto , Idoso , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Análise de Regressão , Testes de Função Respiratória/métodos , Índice de Gravidade de Doença , Lesão Pulmonar Induzida por Ventilação Mecânica/etiologiaRESUMO
Sedation and analgesia are important components of care for the mechanically ventilated patient in the intensive care unit (ICU). An understanding of commonly used medications is essential to formulate a sedation plan for individual patients. The specific physiological changes that a critically ill patient undergoes can have direct effects on the pharmacology of drugs, potentially leading to interpatient differences in response. Objective assessments of pain, sedation, and agitation have been validated for use in the ICU for assessment and titration of medications. An evidence-based strategy for administering these drugs can lead to improvements in short- and long-term outcomes for patients. In this article, we review advances in the field of ICU sedation to provide an up-to-date perspective on management of the mechanically ventilated ICU patient.
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Analgesia , Sedação Consciente , Respiração Artificial , Analgesia/métodos , Sedação Consciente/métodos , Delírio/prevenção & controle , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/uso terapêutico , Unidades de Terapia Intensiva , Agitação Psicomotora/tratamento farmacológico , Respiração Artificial/efeitos adversos , Respiração Artificial/métodosRESUMO
Background and Objective: Cystic fibrosis (CF) is a disorder that affects the cystic fibrosis transmembrane conductance regulator (CFTR). Without properly functioning CFTR channels, chloride does not exit respiratory epithelial cells, and consequently the mucus lining the surface of the cells becomes thick. This viscous mucus accumulates and causes abnormal function of the mucociliary apparatus, which can lead to bacterial colonization, infections with Staphylococcus aureus (S. aureus) and Pseudomonas aeruginosa (P. aeruginosa), and eventually lung damage. Recent studies have shown that the increased susceptibility to respiratory infections in CF patients may also be due to defects in neutrophil function, but the exact mechanism is uncertain. Methods: The PubMed database was searched on February 10, 2023 and again on July 23, 2023 to compile a comprehensive list of clinical and experimental studies to evaluate neutrophil function in CF. The first search included a combination of MeSH terms: "cystic fibrosis" and "neutrophils/physiology". A separate second search included a combination of the MeSH terms: "neutrophils" and "cystic fibrosis transmembrane conductance regulator". Key Content and Findings: Neutrophils from patients with CF have decreased transfer of chloride into phagolysosomes after bacterial ingestion and have dysregulated degranulation. This reduces the production of toxic oxidative radicals, especially hypochlorous acid (HOCl), and reduces bactericidal activity. CFTR potentiators correct the dysregulated degranulation in patients with CF and increased neutrophil killing activity. A reduced concentration of chloride in in vitro assays also reduces neutrophil killing activity; these observations are relevant to the reduced chloride concentrations in respiratory secretions in patients with CF. Conclusions: This literature review summarizes studies that demonstrate that an important defect in CF neutrophils lies in the oxygen-dependent pathway in phagolysosomes and studies with ivacaftor demonstrate that this drug corrects CF neutrophil function. These studies demonstrate the potential utility of using easily available neutrophils to study drug effects in CF patients.
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Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody-drug conjugates, PARP inhibitors, and epigenetic modulators. Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody-drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward. Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody-drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes. However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity. Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients.