RESUMO
Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.008), anti-phosphatidylserine/prothrombin (aPS/PT) IgG (p < 0.001), and aPS/PT IgM (p < 0.001) were significantly associated with venous thrombosis. Positive anti-D1 IgG (p < 0.001), aPS/PT IgG (p < 0.001), and aPS/PT IgM (p = 0.001) were also associated with non-thrombotic manifestations of APS, such as thrombocytopenia. Increased levels of calprotectin were detected in children with APS. Calprotectin correlated positively with absolute neutrophil count (r = 0.63, p = 0.008) and negatively with platelet count (r = -0.59, p = 0.015). Mechanistically, plasma from pediatric APS patients with high calprotectin levels impaired platelet viability in a dose-dependent manner.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Humanos , Criança , Biomarcadores , beta 2-Glicoproteína I , Imunoglobulina G , Imunoglobulina M , Protrombina , Complexo Antígeno L1 LeucocitárioRESUMO
This review focuses on significant advances in the field of pediatric hemostasis and thrombosis, with a focus on published studies within the past decade. The evaluation and management of patients with excessive bleeding remain cornerstones of consultative hematology. We will describe the development of validated bleeding assessment tools relevant to pediatric practice, laboratory advances in the evaluation of von Willebrand disease, and a shift in clinical practice regarding the interpretation of normal coagulation studies in patients with significant bleeding phenotypes. There have also been critical advances in the management of hemostatic disorders. This review highlights new treatment paradigms in hemophilia and the rise of multidisciplinary medical homes for women living with bleeding disorders. Given the continued increase in the incidence of thrombosis, particularly in the hospital setting, a full call to arms against pediatric venous thromboembolism is now essential. We will describe recently completed clinical trials of direct oral anticoagulants in children and adolescents and ongoing work to elucidate the appropriate duration of therapy for children with provoked thrombosis. Recent work regarding the prevention of pediatric venous thromboembolism is highlighted, including studies of thromboprophylaxis and the development of risk prediction models for hospital-acquired thrombosis. Finally, we review advances in our understanding of thrombotic sequelae and the need for continued refinement of our evaluation tools. Despite the significant advances in pediatric hemostasis and thrombosis over the past decade, many unanswered questions remain for the next generation of investigators.
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Hemostáticos , Trombose , Tromboembolia Venosa , Doenças de von Willebrand , Anticoagulantes/uso terapêutico , Feminino , Hemorragia/tratamento farmacológico , Hemostasia , Hemostáticos/uso terapêutico , Humanos , Tromboembolia Venosa/tratamento farmacológico , Tromboembolia Venosa/etiologia , Doenças de von Willebrand/tratamento farmacológico , Doenças de von Willebrand/terapiaRESUMO
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.
Assuntos
COVID-19/complicações , Síndrome de Resposta Inflamatória Sistêmica/complicações , Trombose/etiologia , Adolescente , Adulto , Fatores Etários , Anticoagulantes/uso terapêutico , COVID-19/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Adulto JovemRESUMO
Iron deficiency anemia is associated with heavy menstrual bleeding (HMB) and, by extension, a bleeding disorder (BD). It is unknown if iron deficiency without anemia is associated with a BD in adolescents. Moreover, the threshold of ferritin associated with fatigue in adolescents with HMB is unclear. In this multicenter study, we enrolled adolescents with HMB without BD. Participants underwent BD and anemia work-up in Young Women's Hematology Clinics and completed the Peds QL™ fatigue scale. BDs were defined as von Willebrand Disease, platelet function defect, clotting factor deficiencies, and hypermobility syndrome. Two hundred and fifty consecutive adolescents were enrolled, of whom 196 met eligibility criteria. Overall, 43% (95% confidence interval: 36%-50%) were diagnosed with BD. A total of 61% (n = 119) had serum ferritin levels < 15 ng/mL, 23.5% (n = 46) had iron deficiency only, and 37% (n = 73) had iron deficiency anemia. Low ferritin or ferritin dichotomized as < 15 or ≥ 15 ng/mL was not associated with BD on univariable analysis (p = .24) or when accounting for age, race, ethnicity, body mass index, and hemoglobin (p = .35). A total of 85% had total fatigue score below the population mean of 80.5, and 52% (n = 102) were > 2 SD (or < 54) below the mean, the cut-off associated with severe fatigue. A ferritin threshold of < 6 ng/mL had a specificity of 79.8% but a sensitivity of 36% for severe fatigue. In conclusion, iron deficiency without anemia is not a predictor of BD in adolescents with HMB in a specialty setting. Severe fatigue, especially sleep fatigue, is prevalent in adolescents with BD. Ferritin of < 6 ng/mL has ~80% specificity for severe fatigue in adolescents with HMB.
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Fadiga/complicações , Transtornos Hemorrágicos/complicações , Deficiências de Ferro/complicações , Adolescente , Adulto , Fadiga/sangue , Feminino , Ferritinas/análise , Transtornos Hemorrágicos/sangue , Humanos , Deficiências de Ferro/sangue , Masculino , Menorragia/sangue , Menorragia/complicações , Adulto Jovem , Doenças de von Willebrand/sangue , Doenças de von Willebrand/complicaçõesRESUMO
Emicizumab is a recombinant, humanized, and a bispecific monoclonal antibody that bridges activated factor (F) IX and FX in place of FVIII to restore hemostasis in persons with hemophilia A (PHA). Data on the efficacy and safety of emicizumab in young children is limited. Immunologic naivety, physiologically decreased production of vitamin K dependent proteins, specifically FIX, and enhanced clearance of emicizumab in infants may support decreased emicizumab effectiveness. We report on the facilitation of care rendered by using emicizumab in young PHA with inhibitors and extend data on the efficacy and safety in PHA < 3 years.
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Anticorpos Biespecíficos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemofilia A/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , MasculinoRESUMO
OBJECTIVE: To assess physical activity in children following acute venous thromboembolism (VTE), examine predictors of reduced physical activity and its relationship to post-thrombotic syndrome. STUDY DESIGN: Using a case-control study design, we enrolled 44 children with acute VTE, and compared physical activity using the Godin-Shephard Leisure-Time Physical Activity Questionnaire and health-related quality of life at 3 and 6 months after diagnosis relative to 44 age- and sex-matched controls. We assessed post-thrombotic syndrome scores using the Manco-Johnson Instrument to measure symptoms and signs attributed to sequelae of DVT in cases. RESULTS: The physical activity of VTE cases was decreased at 3 months after diagnosis (36.6 ± 29.0 vs 56.8 ± 25.0; P = .002), but the differences disappeared at 6 months (57.5 ± 39.0 vs 56.8 ± 25.0; P = .60) relative to controls. At 3 and 6 months after diagnosis, overall, 70% and 50% of VTE cases were below their pre-VTE physical activity levels; providers did not address physical activity in the majority. In multivariable analysis, physical activity of cases was lower by 32 points for completely veno-occlusive thrombosis at diagnosis, 11 points for a diagnosis of pulmonary embolism relative to DVT, and increased by 0.72 points for every unit increase in health-related quality of life score. Physical activity at 3 months after diagnosis did not predict the short-term risk of post-thrombotic syndrome. CONCLUSIONS: VTE limits physical activity in children in the first 3 months after the acute event, but the differences were nonexistent at 6 months. Only 50 percent of VTE survivors resume their pre-VTE physical activity levels within 6 months after diagnosis.
Assuntos
Exercício Físico , Tromboembolia Venosa/fisiopatologia , Doença Aguda , Adolescente , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Qualidade de Vida , Fatores de TempoRESUMO
Heavy menstrual bleeding is common in adolescents. The frequency and predictors of bleeding disorders in adolescents, especially with anovulatory bleeding, are unknown. Adolescents referred for heavy menstrual bleeding underwent an evaluation of menstrual bleeding patterns, and bleeding disorders determined a priori The primary outcome was the diagnosis of a bleeding disorder. Two groups were compared: anovulatory and ovulatory bleeding. Multivariable logistic regression analysis of baseline characteristics and predictors was performed. Kaplan Meier curves were constructed for the time from the first bleed to bleeding disorder diagnosis. In 200 adolescents, a bleeding disorder was diagnosed in 33% (n=67): low von Willebrand factor levels in 16%, von Willebrand disease in 11%, and qualitative platelet dysfunction in 4.5%. The prevalence of bleeding disorder was similar between ovulatory and anovulatory groups (31% vs 36%; P=0.45). Predictors of bleeding disorder included: younger age at first bleed (OR: 0.83; 95%CI: 0.73, 0.96), Hispanic ethnicity (OR: 2.48; 95%CI: 1.13, 5.05), non-presentation to emergency department for heavy bleeding (OR: 0.14; 95%CI: 0.05, 0.38), and International Society on Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool score ≥4 (OR: 8.27; 95%CI: 2.60, 26.44). Time from onset of the first bleed to diagnosis was two years in the anovulatory, and six years in the ovulatory cohort (log-rank test, P<0.001). There is a high prevalence of bleeding disorders in adolescents with heavy periods, irrespective of the bleeding pattern. Among bleeding disorders, the prevalence of qualitative platelet dysfunction is lower than previously reported.
Assuntos
Transtornos Hemorrágicos , Menorragia , Doenças de von Willebrand , Adolescente , Estudos de Coortes , Feminino , Humanos , Menorragia/diagnóstico , Menorragia/epidemiologia , Estudos ProspectivosRESUMO
INTRODUCTION: Venous and arterial thrombosis is one of the hallmarks of Antiphospholipid Antibody Syndrome (APS). The traditional treatment for individuals with APS and venous thrombosis has been vitamin K antagonists. However, with the widespread use of direct oral anticoagulants (DOACs) there has been conflicting evidence regarding their safety and failure rate as alternatives to warfarin. Reasons for this failure remain elusive. We utilized the thrombin generation assay (TGA) to investigate the anticoagulation efficacy of three different agents in a patient with triple-positive APS to acquire a better understanding of the pathophysiology of APS. METHODS: Blood samples were obtained from a single patient with APS at five distinct time points while on three different anticoagulants: rivaroxaban, warfarin, and enoxaparin. The effects of these anticoagulants on TG potential were evaluated using the TGA. RESULTS: In the presence of thrombomodulin, rivaroxaban had the highest endogenous thrombin potential, thrombin peak, velocity index, and thrombin inactivation velocity (821.9 nMmin, 121.5 nM, 36.44 nM/min, 7.19 nM/min) when compared to warfarin (121-367 nMmin, 13.85-121.5 nM, 3.02-3.85 nM/min, 0.64-4.55 nM/min) and enoxaparin (242-378.8 nM min, 21.33-23.78 nM, 2.87-3.85 nM/min, 0.747-0.784 nM/min). This trend was also observed in the absence of thrombomodulin. CONCLUSIONS: These results suggest that patients with APS treated with rivaroxaban may be at greater risk for thrombosis compared to warfarin or enoxaparin. The findings may provide insight into the recent studies in patients with triple positive APS randomized to different anticoagulants demonstrating high rates of thrombosis with rivaroxaban. Further studies are necessary to elucidate the clinical significance.
Assuntos
Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Trombina/metabolismo , Idoso , Anticoagulantes/farmacologia , Humanos , MasculinoRESUMO
Cellular and plasma interactions underlie hypercoagulability in sickle cell anemia (SCA). In healthy adults, thrombin generation (TG), a biomarker of hypercoagulability, is similar in plasma with and without platelets. Studies investigating TG in SCA using platelet-poor plasma (PPP) show conflicting results. There are no studies in SCA simultaneously comparing TG using platelet rich plasma (PRP) and PPP. This prospective study compares TG in children with SCA, at steady state, in PPP versus PRP and investigates the association of predefined clinical variables with the difference between PRP and PPP. Our secondary aim was to investigate derangements in the protein C and S pathway measuring TG with and without thrombomodulin (TM). In forty-three paired samples from SCA patients, aged 2-15 years, TG in the presence of platelets was 5.9 % higher [1239 nmol/(min*L) (SD: 224.1) vs. 1151 nmol/(min*L) (SD 223.3); p = 0.026]. The difference was highest in the 6-10 year age group (9.5 %; SD 14.1) followed by the 2-5 year age group (5.4 %; SD 21.4). In a multiple linear regression model, age, gender, current use of hydroxyurea, degree of hemolysis and severity of pain crises were not predictive of the difference between PRP and PPP. In PPP, TG reduction after TM addition was 7.4 % (SD 16.8), signifying activated protein C resistance. In conclusion, TG in children with SCA aged 2-10 years is higher in the presence of platelets. TG using PRP along with TM addition may be a useful biomarker of hypercoagulability in this population.
Assuntos
Anemia Falciforme/sangue , Plaquetas/metabolismo , Trombina/metabolismo , Adolescente , Anemia Falciforme/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate risk factors for hemolysis in pediatric extracorporeal life support. DESIGN: Retrospective, single-center study. SETTING: Pediatric intensive care unit. PATIENTS: Two hundred thirty-six children who received extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Risk factors for hemolysis were retrospectively analyzed from a single center in a total of 236 neonatal and pediatric patients who received extracorporeal membrane oxygenation support (ECMO). There was no difference in the incidence of hemolysis between centrifugal (127 patients) and roller head (109 patients) pump type or between venoarterial and venovenous ECMO. High hemoglobin (Hb) was found to be an independent risk factor for hemolysis in both pump types. The Hb level >12 g/dL was significant in the roller group and the Hb level >13 g/dL was significant in the centrifugal group for the development of hemolysis for the cumulative ECMO run. The presence of high Hb levels on any given day increased the risk of hemolysis for that day of the ECMO run regardless of ECMO pump type. Higher revolutions per minute (RPMs) and higher inlet pressures on any given day increased the risk for the development of hemolysis in the centrifugal pump. Lower inlet venous pressures and RPMs were not associated with hemolysis in the roller group. CONCLUSIONS: An Hb level greater than 13 g/dL was associated with an increased risk of hemolysis, and a high Hb on a given day was associated with a significantly higher risk of hemolysis on the same day. Higher RPMs and lower inlet venous pressures were associated with an increased risk of hemolysis in the centrifugal pump only.
Assuntos
Oxigenação por Membrana Extracorpórea/métodos , Hemoglobinas/metabolismo , Hemólise , Hérnias Diafragmáticas Congênitas/terapia , Síndrome de Aspiração de Mecônio/terapia , Síndrome da Persistência do Padrão de Circulação Fetal/terapia , Adolescente , Criança , Pré-Escolar , Terapia de Substituição Renal Contínua/estatística & dados numéricos , Transfusão de Eritrócitos/estatística & dados numéricos , Oxigenação por Membrana Extracorpórea/instrumentação , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica , Masculino , Análise Multivariada , Pressão , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
OBJECTIVE: To understand the predictive role of perceived mother, father and peer attachment in depressive symptoms of adolescents living with fathers diagnosed with substance use disorder. METHODS: The quantitative study was conducted at various drug rehabilitation centres in Karachi from January 2016 to September 2017, and comprised adolescents living with fathers diagnosed with substance use disorder. Inventory of Parent and Peer Attachment-Revised, Urdu version, and Centre for Epidemiological Studies- Depression Scale for Children, Urdu Version, were used to gather data which was analysed using SPPS 20. RESULTS: Of the 150 participants, 82(55%) were males and 68(45%) were females. The overall mean age was 13.44}1.50 years. Perceived attachment with mother, father and peers collectively contributed significant variance in the depressive symptoms of the subjects (p=0.0001). Independently, only perceived mother and father attachment played a significant role in such symptoms with highest prediction value observed on father attachment (p<0.05). CONCLUSIONS: Perceived mother and father attachment were found to be significant predictors of depressive symptoms among adolescents living with paternal substance use disorder. Peer attachment was significantly linked to the symptoms, but did not have a definite predictive role.
Assuntos
Depressão , Relações Pai-Filho , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Criança , Pai , Feminino , Humanos , Masculino , Mães , Paquistão , Grupo AssociadoRESUMO
OBJECTIVE: The management of pain is an important component of care in the prehospital and transport setting. However, recent evidence suggests that pain control is infrequently achieved in these settings. The objective of the current study was to determine the proportion and frequency of opioid analgesia provided to intubated patients during interfacility transport by an air medical transport system. METHODS: This was a health records review examining electronic records of intubated patients transported by Ornge from July 2015 to November 2015. Cases were identified using Ornge database, and intubated patients were selected based on the inclusion criteria. A standardized data extraction form was piloted and used by a single trained data extractor. The primary outcome was whether analgesia was provided. Secondary outcomes included the frequency of administration and dose adequacy of an opioid analgesia; the analgesic used; adverse events; and the impact of age, sex, past medical history of chronic pain, or reason for transfer on pain management. RESULTS: Of the 500 potential patient transports, 448 met our inclusion criteria. Among the 448 patients, 295 (65.8%) were men, 327 (73.0%) received analgesia, and 211 (64.3%) received more than 1 dose during transport (median frequency of 2 doses, interquartile rangeâ¯=â¯1 to 3). The average transport time was 135 minutes, and repeated dosing (> 1 repeat dose) occurred primarily (45.5%) in transports of over 180 minutes. Fentanyl was the most commonly used analgesic (97.9%), and the most common dose was 50 µg (51.8%). Adverse events occurred in 8 patients (2.5%), most commonly new hypotension (mean arterial pressure < 65 mm Hg, nâ¯=â¯5). There was no significant difference in the administration of analgesia based on the patient's age or sex (68.0% of female patients and 75.6% of male patients received analgesia). Interestingly, only 30.8% of patients repatriated to their originating hospital received analgesia compared with 72.3% of patients undergoing their initial transfer to a higher level of care. CONCLUSION: Seventy-three percent of intubated patients transported by Ornge received an opioid analgesic, most commonly fentanyl. We found no clinically relevant difference in the administration of analgesics based on age, sex, past medical history of chronic pain, or reason for transfer other than repatriation to the originating hospital.
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Intubação , Manejo da Dor , Transporte de Pacientes , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Registros Eletrônicos de Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: Heavy menstrual bleeding (HMB) may be expected for many adolescents after menarche. Accurate assessment of HMB, a key component in the diagnosis of a haemostatic defect (HD), is a well-recognized challenge. AIM: Our objective was to determine the diagnostic accuracy of an HMB-specific screening tool for HDs in adolescents with HMB, presenting to a secondary care setting. METHODS: Adolescents with HMB were evaluated for a HD at 4 US centres. A screening tool, the Philipp Tool, developed and validated in adult women with HMB, was administered. We modified the tool by assigning a score based on the number of affirmative responses. Sensitivity, specificity and likelihood ratios (LRs) of a positive tool, modified tool, with a pictorial blood assessment chart (PBAC) score >185, and with serum ferritin ≤20 ng/mL were calculated for HDs. RESULTS: Among 248 adolescents with HMB, 29% were diagnosed with HDs. Sensitivity, specificity and LR of a positive screening tool for HDs were 95% (range 88-99), 14% (9-21) and 1.1 (1-1.2), respectively. A score of ≥2, addition of a PBAC score >185 and ferritin ≤20 ng/mL changed the sensitivity, specificity and LR of the tool to 72% (61-81), 94% (83-99), 76% (65-85); 60% (53-68), 24% (16-34) and 39% (31-47) and 1.8 (1.4-2.2), 1.2 (1.1-1.4) and 1.2 (1-1.4), respectively. CONCLUSION: Although sensitive, the discriminative ability of the tool to identify adolescents with HDs from those without, who presented with HMB, was low. Further research is needed to optimize or develop an adolescent-specific HMB tool for secondary care settings.
Assuntos
Hemostasia , Programas de Rastreamento , Menorragia/diagnóstico , Menorragia/fisiopatologia , Adolescente , Criança , Estudos de Coortes , Feminino , HumanosRESUMO
STUDY OBJECTIVE: Emergency department (ED) visits for hypertension are rapidly increasing. Hypertension guidelines began recommending use of self-measurement blood pressure (BP) devices in the early 2000s, which could be contributing to the increase. We aim to examine the proportion of ED visits for hypertension that occurred after a BP measurement with a self-measuring device, and the associated outcomes. METHODS: This retrospective observational study included adults who made an ED visit and received a primary diagnosis of hypertension at 1 of 5 community and tertiary hospitals in Ontario, Canada, between April 2010 and March 2011. We categorized ED visits into 4 groups: those made after a home BP reading, a pharmacy reading, as a result of a physician referral, and all others (termed "not documented"). We examined rates of admission to the hospital, ED treatment (administration of antihypertensive medication and prescription provision), and post-ED clinical events (follow-up care, return ED visits, and long-term all-cause mortality) by group. RESULTS: Among 1,508 qualifying patients, median presenting ED BP was 182/97 mm Hg (interquartile range 164 to 200/85 to 109 mm Hg). The percentage of patients who presented to the ED after a reading at home, at a pharmacy, or by physician referral and the remaining patients not documented was 40.9%, 8.3%, 13.3%, and 37.5%, respectively. Overall, 109 patients (7.2%) were admitted to the hospital. The proportion of patients admitted after a home or pharmacy reading, after a physician referral, or who were not documented was 3.1%, 11.9%, and 11.0%, respectively. Two-year mortality rates were 5.4%, 0.0%, 6.5%, and 5.3% for the home, pharmacy, physician referral, and not documented groups, respectively. Among the 92.8% of patients who were discharged from the ED, 11% made another ED visit for hypertension within a year. CONCLUSION: In this study, half of patients with an ED visit that was primarily for hypertension presented after elevated readings on self-measurement devices. Only 3% of these patients were admitted to the hospital.
Assuntos
Assistência Ambulatorial/estatística & dados numéricos , Determinação da Pressão Arterial/instrumentação , Hipertensão/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Humanos , Masculino , Ontário , Estudos RetrospectivosRESUMO
The discovery that oxidized vitamin C, dehydroascorbate (DHA), can induce oxidative stress and cell death in cancer cells has rekindled interest in the use of high dose vitamin C (VC) as a cancer therapy. However, high dose VC has shown limited efficacy in clinical trials, possibly due to the decreased bioavailability of oral VC. Because human erythrocytes express high levels of Glut1, take up DHA, and reduce it to VC, we tested how erythrocytes might impact high dose VC therapies. Cancer cells are protected from VC-mediated cell death when co-cultured with physiologically relevant numbers of erythrocytes. Pharmacological doses of VC induce oxidative stress, GSH depletion, and increased glucose flux through the oxidative pentose phosphate pathway (PPP) in erythrocytes. Incubation of erythrocytes with VC induced hemolysis, which was exacerbated in erythrocytes from glucose-6-phosphate dehydrogenase (G6PD) patients and rescued by antioxidants. Thus, erythrocytes protect cancer cells from VC-induced oxidative stress and undergo hemolysis in vitro, despite activation of the PPP. These results have implications on the use of high dose VC in ongoing clinical trials and highlight the importance of the PPP in the response to oxidative stress.
Assuntos
Ácido Ascórbico/efeitos adversos , Eritrócitos/citologia , Glutationa/metabolismo , Neoplasias/metabolismo , Estresse Oxidativo , Via de Pentose Fosfato , Ácido Ascórbico/metabolismo , Linhagem Celular Tumoral , Ácido Desidroascórbico/efeitos adversos , Ácido Desidroascórbico/metabolismo , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Hemólise/efeitos dos fármacos , Humanos , Neoplasias/enzimologia , Neoplasias/genética , Oxirredução , Estresse Oxidativo/efeitos dos fármacosRESUMO
Oral contraceptive (OCP) induced changes on coagulation are complex with high inter-individual variability. The precise reason for differences in this variability is unknown. We hypothesized that global coagulation assays better delineate these changes and variability in hypercoagulability may be the result of differences in estrogen metabolism and thrombophilia. Fifty-two adolescents initiating OCPs were prospectively enrolled; 33 subjects completed the study. Samples were analyzed prior to and after OCPs for procoagulant and anticoagulant factor activities and thrombin generation (TG) +/-thrombomodulin. Participants were genotyped for common thrombophilia and estrogen receptor-α (ESR-α) single nucleotide polymorphisms (SNPs). SNP genotypes were compared to coagulation parameters; TG parameters and differences pre and post OCPs were examined. At baseline, a striking finding was elevated FVIII levels. FVL was absent in all and F2 G20210A was present in one participant. The ESR-α polymorphism was present in heterozygous state in 59% and homozygous state in 21% participants. There were no differences in VWF levels and FVIII: C after being on OCPs. Protein S levels decreased with OCPs. Sixty percent of participants showed evidence of hypercoagulability on TG testing on OCPs. Higher thrombin peak and endogenous thrombin potential (ETP) were seen on TG after OCPs. With thrombomodulin, ETP and thrombin peak did not decrease after OCPs, signifying 'thrombomodulin resistance'. We demonstrated that OCPs induce a state of "variable" hypercoagulability in adolescents, predominantly through the protein S pathway. Genetic and nongenetic factors may account for the variable increase in hypercoagulability. Further research is needed to understand this.
Assuntos
Anticoncepcionais Orais/efeitos adversos , Receptor alfa de Estrogênio/genética , Etinilestradiol/efeitos adversos , Norgestrel/análogos & derivados , Polimorfismo de Nucleotídeo Único , Trombofilia/sangue , Adolescente , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Fator V/genética , Fator V/metabolismo , Fator VIII/genética , Fator VIII/metabolismo , Feminino , Expressão Gênica , Heterozigoto , Homozigoto , Humanos , Norgestrel/efeitos adversos , Proteína S/genética , Proteína S/metabolismo , Trombina/metabolismo , Trombomodulina/sangue , Trombofilia/induzido quimicamente , Trombofilia/genética , Adulto Jovem , Fator de von Willebrand/genética , Fator de von Willebrand/metabolismoRESUMO
We investigated whether pediatric patients with overweight and obesity are more likely to have dyspnea compared with those who are non-overweight. We collected de-identified data from TriNetX, a global federated multicenter research database, using both the UT Southwestern Medical Center and multinational Research Networks. Our analysis focused on patients aged 8-12 years. We identified overweight and obesity using ICD-10-CM codes E66 and dyspnea using code R06.0. Patients with overweight and obesity had a significantly higher risk of dyspnea compared with those who were non-overweight. This association was observed in both the UT Southwestern Network (risk ratio: 1.81, p < 0.001) and the Research Network (risk ratio: 2.70, p < 0.001). Furthermore, within the UT Southwestern Network, the risk was found to be higher in females compared with males (risk ratio: 2.17 vs. 1.67). These results have significant clinical implications, suggesting that clinicians should consider overweight and obesity as independent risk factors for dyspnea in pediatric patients after excluding other possible contributing factors.
Assuntos
Obesidade , Sobrepeso , Masculino , Feminino , Humanos , Criança , Sobrepeso/complicações , Sobrepeso/epidemiologia , Obesidade/complicações , Fatores de Risco , Dispneia/diagnóstico , Índice de Massa CorporalRESUMO
INTRODUCTION: Women-identifying emergency physicians face gender-based discrimination throughout their careers. The purpose of this study was to explore emergency physician's perceptions and experiences of gender equity in emergency medicine. METHODS: We conducted a secondary analysis of data from a previously conducted survey of Canadian emergency physicians on barriers to gender equity in emergency medicine. Survey responses were analyzed using logistic regression to determine the impact that gender, practice setting, years since graduation, race, equity-seeking status, and parental status had on agreement about gender equity in emergency medicine and five of the problem statements. RESULTS: A total of 710 participants completed the survey. Most identified as women (58.8%), white (77.4%), graduated between 2010 and 2019 (40%), had CCFP (Emergency Medicine) designation (47.9%), an urban practice (84.4%), were parents (62.4%) and did not identify as equity-seeking (79.9%). Women-identifying physicians were less likely to perceive gender equity in emergency medicine, OR 0.52, CI [0.38, 0.73]. Women-identifying physicians were more likely to agree with statements about microaggressions, OR 4.39, CI [2.66, 7.23]; barriers to leadership, OR 3.51, CI [2.25, 5.50]; gender wage gap, OR 13.46, CI [8.27, 21.91]; lack of support for parental leave, OR 2.85, CI [1.82, 4.44]; and education on allyship, OR 2.23 CI [1.44, 3.45] than men-identifying physicians. CONCLUSION: In this study, women-identifying physicians were less likely to perceive that there was gender equity in emergency medicine than men-identifying physicians. Women-identifying physicians agreed that there are greater barriers for career advancement including fewer opportunities for leadership, a gender wage gap, a lack of parental leave policies to support a return to work and a lack of education for men to become allies. Men-identifying physicians were less aware of these inequities. Health systems must work to improve gender equity in emergency medicine and this will require education and allyship from men-identifying physicians.
RéSUMé: INTRODUCTION: Les femmes médecins urgentistes sont confrontées à une discrimination fondée sur le sexe tout au long de leur carrière. L'objectif de cette étude était d'explorer les perceptions et les expériences des médecins urgentistes en matière d'équité entre les sexes en médecine d'urgence. MéTHODES: Nous avons procédé à une analyse secondaire des données d'une enquête menée précédemment auprès des médecins urgentistes canadiens sur les obstacles à l'équité entre les sexes en médecine d'urgence. Les réponses au sondage ont été analysées à l'aide d'une régression logistique pour déterminer l'incidence que le sexe, le milieu de pratique, les années écoulées depuis l'obtention du diplôme, la race, le statut de demandeur d'équité et le statut parental avaient sur l'accord sur l'équité entre les sexes en médecine d'urgence et cinq des énoncés de problème. RéSULTATS: Au total, 710 participants ont répondu à l'enquête. La plupart d'entre eux sont des femmes (58.8 %), de race blanche (77.4 %), ont obtenu leur diplôme entre 2010 et 2019 (40 %), ont le titre de CCMF (médecine d'urgence) (47.9 %), exercent en milieu urbain (84.4 %), sont parents (62.4 %) et ne se déclarent pas en quête d'équité (79.9 %). Les médecins s'identifiant à des femmes étaient moins susceptibles de percevoir l'équité entre les sexes en médecine d'urgence, OR 0.52, IC [0.38,0.73]. Les médecins s'identifiant comme femmes étaient plus susceptibles d'être d'accord avec les déclarations sur les microagressions, OR 4.39, IC [2.66, 7.23] ; obstacles au leadership, OR 3.51, IC [2.25, 5.50] ; écart salarial entre les hommes et les femmes, OR 13.46, IC [8.27, 21.91] ; le manque de soutien pour le congé parental, OR 2.85, IC [1.82, 4.44]; et l'éducation sur l'alliance, OR 2.23 IC [1.44, 3.45] que les médecins s'identifiant comme hommes. CONCLUSION: Dans cette étude, les médecins s'identifiant à des femmes étaient moins susceptibles de percevoir qu'il y avait une équité entre les sexes en médecine d'urgence que les médecins s'identifiant à des hommes. Les femmes médecins s'accordent à dire qu'il existe davantage d'obstacles à l'avancement professionnel, notamment moins d'opportunités de leadership, un écart salarial entre les hommes et les femmes, un manque de politiques de congé parental pour favoriser le retour au travail et un manque d'éducation des hommes pour qu'ils deviennent des alliés. Les médecins s'identifiant à des hommes étaient moins conscients de ces inégalités. Les systèmes de santé doivent s'efforcer d'améliorer l'équité entre les sexes dans la médecine d'urgence, ce qui nécessitera une formation et un allié de la part des médecins qui s'identifient aux hommes.