RESUMO
Immune thrombocytopenia (ITP) is an autoimmune disease typically associated with severely depleted platelet counts. However, additional symptoms (e.g. increased fatigue and memory/concentration difficulties) can profoundly impact patients' quality of life. The nature and severity of cognitive impairment in ITP, and potential association with patient/disease characteristics were evaluated in 49 adults with relapsed/refractory ITP. The Cogstate Brief Battery quantitatively assessed psychomotor function (DET), attention (IDN), visual learning (OCL) and working memory (ONB) individually, as well as DET/IDN and OCL/ONB composites. Clinically important cognitive impairment (defined as z-score ≤ -1) for ≥2 individual tests was observed in 29 patients (59%). Impairment was highest for IDN (67% of patients), followed by DET (53%), ONB (39%) and OCL (16%). A higher magnitude of impairment was observed for the DET/IDN composite (mean z-score -1.54; 95% CI, -1.94 to -1.13) than OCL/ONB (mean z-score -0.21; 95% CI, -0.49 to 0.07). The severity of cognitive impairment was comparable to mild traumatic brain injury and associated with increasing age and fatigue but unrelated to platelet count or corticosteroid use. Overall, these results warrant a clinical need to further consider the potential of cognitive dysfunction in assessing ITP patients.
Assuntos
Disfunção Cognitiva , Púrpura Trombocitopênica Idiopática , Humanos , Púrpura Trombocitopênica Idiopática/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Disfunção Cognitiva/etiologia , Adulto , Idoso , Doença Crônica , Idoso de 80 Anos ou maisRESUMO
Patients with cold agglutinin disease (CAD) are more vulnerable to infectious agents, thus the COVID-19 pandemic has posed a particular risk to this population. Sutimlimab Phase 3 studies CARDINAL and CADENZA spanned the period before and during the pandemic; investigators were advised to vaccinate enrolled patients without stopping treatment. Of 61 completers from both studies, 47 received ≥1 dose of a COVID-19 vaccine. In the immunogenicity analysis (n = 27) all patients developed an immune response post-COVID-19 vaccination, with detectable immunoglobulin G anti-spike antibodies. Analysis of six patients with booster vaccinations demonstrated increased immune responses pre- to post-booster. COVID-19 vaccines were well tolerated in patients with CAD receiving sutimlimab treatment, and no signs of hemolytic exacerbations were observed post-vaccination.
Assuntos
Anemia Hemolítica Autoimune , Anticorpos Monoclonais Humanizados , COVID-19 , Humanos , Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Pandemias , Anticorpos AntiviraisRESUMO
RATIONALE: Cystic fibrosis (CF) is characterized by dietary antioxidant deficiencies, which may contribute to an oxidant-antioxidant imbalance and oxidative stress. OBJECTIVES: Evaluate the effects of an oral antioxidant-enriched multivitamin supplement on antioxidant concentrations, markers of inflammation and oxidative stress, and clinical outcomes. METHODS: In this investigator-initiated, multicenter, randomized, double-blind, controlled trial, 73 pancreatic-insufficient subjects with CF 10 years of age and older with an FEV1 between 40% and 100% predicted were randomized to 16 weeks of an antioxidant-enriched multivitamin or control multivitamin without antioxidant enrichment. Endpoints included systemic antioxidant concentrations, markers of inflammation and oxidative stress, clinical outcomes (pulmonary exacerbations, anthropometric measures, pulmonary function), safety, and tolerability. MEASUREMENTS AND MAIN RESULTS: Change in sputum myeloperoxidase concentration over 16 weeks, the primary efficacy endpoint, was not significantly different between the treated and control groups. Systemic antioxidant (ß-carotene, coenzyme Q10, γ-tocopherol, and lutein) concentrations significantly increased in the antioxidant-treated group (P < 0.001 for each), whereas circulating calprotectin and myeloperoxidase decreased in the treated group compared with the control group at Week 4. The treated group had a lower risk of first pulmonary exacerbation requiring antibiotics than the control group (adjusted hazard ratio, 0.50; P = 0.04). Lung function and growth endpoints did not differ between groups. Adverse events and tolerability were similar between groups. CONCLUSIONS: Antioxidant supplementation was safe and well tolerated, resulting in increased systemic antioxidant concentrations and modest reductions in systemic inflammation after 4 weeks. Antioxidant treatment was also associated with a lower risk of first pulmonary exacerbation. Clinical trial registered with www.clinicaltrials.gov (NCT01859390).
Assuntos
Antioxidantes/uso terapêutico , Fibrose Cística/complicações , Suplementos Nutricionais , Desnutrição/complicações , Desnutrição/tratamento farmacológico , Vitaminas/uso terapêutico , Administração Oral , Adolescente , Adulto , Criança , Método Duplo-Cego , Feminino , Humanos , Inflamação/complicações , Inflamação/tratamento farmacológico , Masculino , Estresse Oxidativo , Adulto JovemRESUMO
RATIONALE: Individuals with cystic fibrosis (CF) experience frequent acute pulmonary exacerbations, which lead to decreased lung function and reduced quality of life. OBJECTIVES: The goal of this study was to determine if an intervention directed toward early detection of pulmonary exacerbations using home spirometry and symptom monitoring would result in slower decline in lung function than in control subjects. METHODS: We conducted a multicenter, randomized trial at 14 CF centers with subjects at least 14 years old. The early intervention arm subjects measured home spirometry and symptoms electronically twice per week. Sites were notified if a participant met criteria for an exacerbation and contacted participants to determine if treatment for acute exacerbation was required. Participants in the usual care arm were seen every 3 months and were asked to contact the site if they were concerned about worsening pulmonary symptoms. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the 52-week change in FEV1. Secondary outcomes included time to first exacerbation and subsequent exacerbation, quality of life, and change in weight. A total of 267 patients were randomized, and the study arms were well matched at baseline. There was no significant difference between study arms in 52-week mean change in FEV1 slope (mean slope difference, 0.00 L, 95% confidence interval, -0.07 to 0.07; P = 0.99). The early intervention arm subjects detected exacerbations more frequently than usual care arm subjects (time to first exacerbation hazard ratio, 1.45; 95% confidence interval, 1.09 to 1.93; P = 0.01). Adverse events were not significantly different between treatment arms. CONCLUSIONS: An intervention of home monitoring among patients with CF was able to detect more exacerbations than usual care, but this did not result in slower decline in lung function. Clinical trial registered with www.clinicaltrials.gov (NCT01104402).
Assuntos
Fibrose Cística/fisiopatologia , Pulmão/fisiopatologia , Autocuidado/métodos , Adulto , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Masculino , Espirometria/métodosRESUMO
BACKGROUND.: Characterization of the role of respiratory viral pathogens on cystic fibrosis (CF) pulmonary disease is needed. We aimed to determine the association of influenza and respiratory syncytial virus (RSV) activity with risk of pulmonary exacerbation (PEx) in persons with CF in the United States. METHODS.: We conducted a cohort study from January 2003 to March 2009 using the CF Foundation Patient Registry merged with Centers for Disease Control and Prevention respiratory virus surveillance data. The primary goal was to determine the association between regional influenza or RSV detections with risk of PEx requiring intravenous antibiotics or hospitalization. We analyzed outcomes by geographic region and week of event using multivariable regression models adjusted for demographic and clinical predictors of PEx stratified for children (<18 years) and adults (≥18 years) to calculate relative risks (RRs) of PEx. RESULTS.: There were 21022 individuals (52% male) in the CF patient cohort in 2003 comprised of 12702 children and 8320 adults. The overall incidence rate of PEx was 521.9 per 10000 person-months. In children, a 10% increase in the proportion of surveillance tests positive for influenza or RSV was significantly associated with increased PEx risk (RR, 1.02; 95% confidence interval [CI], 1.01-1.03) and (RR, 1.05; 95% CI, 1.02-1.07), respectively. In adults, surveillance tests positive for influenza (RR, 1.02; 95% CI, 1.01-1.02), but not RSV (RR, 0.99; 95% CI, .98-1.01), had a significant association with PEx risk. CONCLUSIONS.: Our large CF population-based cohort demonstrated a significant association between PEx risk and influenza activity in children and adults and with RSV activity in children.
Assuntos
Fibrose Cística/complicações , Fibrose Cística/fisiopatologia , Influenza Humana/complicações , Pulmão/virologia , Infecções por Vírus Respiratório Sincicial/complicações , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Estudos de Coortes , Fibrose Cística/virologia , Progressão da Doença , Monitoramento Epidemiológico , Feminino , Hospitalização , Humanos , Incidência , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros , Fatores de Risco , Adulto JovemRESUMO
Student selection for Undergraduate Medical Education Programmes (UGME) is a highly selective process globally. Health care practice requires many attributes like communication skills, professionalism, critical thinking and problem solving in addition to cognitive abilities. This study reports the development and administration of Multiple Mini Interviews (MMI), the descriptive and psychometric properties of the MMI station scores and assesses the validity of MMI stations to ascertain if the stations measured the intended attributes. Nine attributes considered most essential for a successful health care professional were selected. A 5 point rating scale was used to rate each item on the station. The scores were then converted into percentage scores. The mean scores on each MMI station ranged from 27.4% to 80.0%. The reliability of stations using Cronbach's alpha ranged from 0.64 to 0.98. MMI can be used to make reliable and valid decisions to select students with desired non cognitive attributes.
Assuntos
Teste de Admissão Acadêmica , Educação de Graduação em Medicina/organização & administração , Psicometria/métodos , Estudantes de Medicina/psicologia , Humanos , Entrevistas como AssuntoRESUMO
BACKGROUND: Ivacaftor improves outcomes in cystic fibrosis (CF) patients with the G551D mutation; however, effects on respiratory microbiology are largely unknown. This study examines changes in CF respiratory pathogens with ivacaftor and correlates them with baseline characteristics and clinical response. METHODS: The G551D Observational Study enrolled a longitudinal observational cohort of US patients with CF aged 6 years and older with at least 1 copy of the G551D mutation. Results were linked with retrospective and prospective culture data in the US Cystic Fibrosis Foundation's National Patient Registry. Pseudomonas aeruginosa infection category in the year before and year after ivacaftor was compared and correlated with clinical findings. RESULTS: Among 151 participants prescribed ivacaftor, 29% (26/89) who were culture positive for P. aeruginosa the year prior to ivacaftor use were culture negative the year following treatment; 88% (52/59) of those P. aeruginosa free remained uninfected. The odds of P. aeruginosa positivity in the year after ivacaftor compared with the year prior were reduced by 35% (odds ratio [OR], 0.65; P < .001). Ivacaftor was also associated with reduced odds of mucoid P. aeruginosa (OR, 0.77; P = .013) and Aspergillus (OR, 0.47; P = .039), but not Staphylococcus aureus or other common CF pathogens. Patients with intermittent culture positivity and higher forced expiratory volume in 1 second (FEV1) were most likely to turn culture negative. Reduction in P. aeruginosa was not associated with change in FEV1, body mass index, or hospitalizations. CONCLUSIONS: Pseudomonas aeruginosa culture positivity was significantly reduced following ivacaftor treatment. Efficacious CFTR modulation may contribute to lower frequency of culture positivity for P. aeruginosa and other respiratory pathogens, particularly in patients with less established disease.
Assuntos
Aminofenóis/uso terapêutico , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Ativadores de Enzimas/uso terapêutico , Infecções por Pseudomonas/epidemiologia , Pseudomonas aeruginosa/isolamento & purificação , Quinolonas/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Aspergillus/isolamento & purificação , Criança , Estudos de Coortes , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Proteínas Mutantes/genética , Mutação de Sentido Incorreto , Prevalência , Infecções por Pseudomonas/microbiologia , Staphylococcus aureus/isolamento & purificação , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
RATIONALE: Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator recently approved for patients with CF age 6 and older with the G551D mutation. OBJECTIVES: To evaluate ivacaftor in a postapproval setting and determine mechanism of action and response of clinically relevant markers. METHODS: We conducted a longitudinal cohort study in 2012-2013 in G551D CF patients age 6 and older with no prior exposure to ivacaftor. Study assessments were performed at baseline, 1, 3, and 6 months after ivacaftor initiation. Substudies evaluated mucociliary clearance, ß-adrenergic sweat secretion rate, gastrointestinal pH, and sputum inflammation and microbiology Measurements and Main Results: A total of 151 of 153 subjects were prescribed ivacaftor and 88% completed the study through 6 months. FEV1 % predicted improved from baseline to 6 months (mean absolute change, 6.7%; P < 0.001). Similarly, body mass index improved from baseline to 6 months (mean change, 0.8 kg/m(2); P < 0.001). Sweat chloride decreased from baseline to 6 months (mean change, -53.8 mmol/L; 95% confidence interval, -57.7 to -49.9; P < 0.001), reflecting augmented CFTR function. There was significant improvement in hospitalization rate (P < 0.001) and Pseudomonas aeruginosa burden (P < 0.01). Significant improvements in mucociliary clearance (P < 0.001), gastrointestinal pH (P = 0.001), and microbiome were also observed, providing clinical mechanisms underlying the therapeutic benefit of ivacaftor. CONCLUSIONS: Significant clinical and physiologic improvements were observed on initiation of ivacaftor in a broad patient population, including reduced infection with P. aeruginosa. Biomarker studies substantially improve the understanding of the mechanistic consequences of CFTR modulation on pulmonary and gastrointestinal physiology.
Assuntos
Aminofenóis/farmacologia , Fibrose Cística/tratamento farmacológico , Intestino Delgado/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Quinolonas/farmacologia , Medicamentos para o Sistema Respiratório/farmacologia , Adolescente , Adulto , Aminofenóis/uso terapêutico , Biomarcadores/metabolismo , Criança , Fibrose Cística/genética , Fibrose Cística/metabolismo , Fibrose Cística/microbiologia , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Seguimentos , Volume Expiratório Forçado/efeitos dos fármacos , Marcadores Genéticos , Hospitalização/estatística & dados numéricos , Humanos , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Intestino Delgado/metabolismo , Pulmão/metabolismo , Pulmão/microbiologia , Pulmão/fisiopatologia , Masculino , Microbiota/efeitos dos fármacos , Depuração Mucociliar/efeitos dos fármacos , Mutação , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/isolamento & purificação , Quinolonas/uso terapêutico , Medicamentos para o Sistema Respiratório/uso terapêutico , Escarro/metabolismo , Escarro/microbiologia , Suor/efeitos dos fármacos , Suor/metabolismo , Resultado do Tratamento , Adulto JovemRESUMO
RATIONALE: Pseudomonas aeruginosa undergoes phenotypic changes during cystic fibrosis (CF) lung infection. Although mucoidy is traditionally associated with transition to chronic infection, we hypothesized that additional in vitro phenotypes correlate with this transition and contribute to disease. OBJECTIVES: To characterize the relationships between in vitro P. aeruginosa phenotypes, infection stage, and clinical outcomes. METHODS: A total of 649 children with CF and newly identified P. aeruginosa were followed for a median 5.4 years during which a total of 2,594 P. aeruginosa isolates were collected. Twenty-six in vitro bacterial phenotypes were assessed among the isolates, including measures of motility, exoproduct production, colony morphology, growth, and metabolism. MEASUREMENTS AND MAIN RESULTS: P. aeruginosa phenotypes present at the time of culture were associated with both stage of infection (new onset, intermittent, or chronic) and the primary clinical outcome, occurrence of a pulmonary exacerbation (PE) in the subsequent 2 years. Two in vitro P. aeruginosa phenotypes best distinguished infection stages: pyoverdine production (31% of new-onset cultures, 48% of intermittent, 69% of chronic) and reduced protease production (31%, 39%, and 65%, respectively). The best P. aeruginosa phenotypic predictors of subsequent occurrence of a PE were mucoidy (odds ratio, 1.75; 95% confidence interval, 1.19-2.57) and reduced twitching motility (odds ratio, 1.43; 95% confidence interval, 1.11-1.84). CONCLUSIONS: In this large epidemiologic study of CF P. aeruginosa adaptation, P. aeruginosa isolates exhibited two in vitro phenotypes that best distinguished early and later infection stages. Among the many phenotypes tested, mucoidy and reduced twitching best predicted subsequent PE. These phenotypes indicate potentially useful prognostic markers of transition to chronic infection and advancing lung disease.
Assuntos
Fibrose Cística/complicações , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Adolescente , Criança , Pré-Escolar , Fibrose Cística/microbiologia , Progressão da Doença , Feminino , Humanos , Técnicas In Vitro , Lactente , Modelos Logísticos , Masculino , Estudos Multicêntricos como Assunto , Avaliação de Resultados em Cuidados de Saúde , Fenótipo , Estudos Prospectivos , Infecções por Pseudomonas/genética , Pseudomonas aeruginosa/isolamento & purificaçãoRESUMO
BACKGROUND: Pseudomonas aeruginosa is a key respiratory pathogen in people with cystic fibrosis (CF). Due to its association with lung disease progression, initial detection of P. aeruginosa in CF respiratory cultures usually results in antibiotic treatment with the goal of eradication. Pseudomonas aeruginosa exhibits many different phenotypes in vitro that could serve as useful prognostic markers, but the relative relationships between these phenotypes and failure to eradicate P. aeruginosa have not been well characterized. METHODS: We measured 22 easily assayed in vitro phenotypes among the baseline P. aeruginosa isolates collected from 194 participants in the 18-month EPIC clinical trial, which assessed outcomes after antibiotic eradication therapy for newly identified P. aeruginosa. We then evaluated the associations between these baseline isolate phenotypes and subsequent outcomes during the trial, including failure to eradicate after antipseudomonal therapy, emergence of mucoidy, and occurrence of an exacerbation. RESULTS: Baseline P. aeruginosa isolates frequently exhibited phenotypes thought to represent chronic adaptation, including mucoidy. Wrinkly colony surface and irregular colony edges were both associated with increased risk of eradication failure (hazard ratios [95% confidence intervals], 1.99 [1.03-3.83] and 2.14 [1.32-3.47], respectively). Phenotypes reflecting defective quorum sensing were significantly associated with subsequent mucoidy, but no phenotype was significantly associated with subsequent exacerbations during the trial. CONCLUSIONS: Pseudomonas aeruginosa phenotypes commonly considered to reflect chronic adaptation were observed frequently among isolates at early detection. We found that 2 easily assayed colony phenotypes were associated with failure to eradicate after antipseudomonal therapy, both of which have been previously associated with altered biofilm formation and defective quorum sensing.
Assuntos
Fibrose Cística/microbiologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Infecções por Pseudomonas/prevenção & controle , Pseudomonas aeruginosa/citologia , Pseudomonas aeruginosa/fisiologia , Biofilmes/efeitos dos fármacos , Criança , Pré-Escolar , Fibrose Cística/complicações , Feminino , Genótipo , Glicosaminoglicanos/análise , Humanos , Lactente , Masculino , Fenótipo , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Falha de TratamentoRESUMO
BACKGROUND: Free tissue transfer is a reliable method for reconstruction of head and neck defects. With the growing number of octogenarians in the population, it is important to understand how these patients respond to these procedures. METHODS: Through a retrospective chart review of patients who underwent a free-flap reconstruction from 2000 to 2010 at an academic medical center, 48 patients, aged 80 years and older, were compared with a control group consisting of 97 similar patients, aged younger than 80 years. We compared the intensive care unit (ICU) length of stay, overall hospital stay, and the incidence of perioperative complications between the cohorts. RESULTS: The average length of stay in the ICU was significantly longer for the octogenarian group as compared with the younger group (101 vs. 41 hours, p-value = 0.007). The average length of hospital stay was not significantly different between the two groups (difference = 40 hours, p-value = 0.102). The incidence of perioperative complication was 75% in the octogenarian group and 60% in the younger group (p-value = 0.095). There were two flap failures in the younger group, and none in the octogenarian group. There was a significantly higher rate of death within 30 days in the octogenarian group. CONCLUSIONS: Microvascular free tissue transfer is a reliable and safe method of reconstruction of head and neck defects in patients over 80 years of age. Patients should be counseled about the potential risks of increased incidence of medical complications, ICU length of stay, and rate of perioperative death when recommended to undergo free tissue transfer reconstruction.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Idoso Fragilizado , Retalhos de Tecido Biológico/irrigação sanguínea , Neoplasias de Cabeça e Pescoço/cirurgia , Tempo de Internação/estatística & dados numéricos , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Comorbidade , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/mortalidade , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Heart failure is a significant cause of morbidity and mortality worldwide. Despite advancements in guideline-directed medical therapy and improvements in device-based therapies, patients with advanced heart failure have high rates of mortality regardless of ejection fraction. For patients with reduced ejection fraction who meet criteria, cardiac resynchronization therapy or implantable cardiac defibrillators are options available to improve outcomes. However, not all heart failure patients meet those criteria. Cardiac contractility modulation is an innovative therapy that serves to improve functional outcomes and quality of life, while also modifying pathologic gene expression and preventing further remodeling. In this article, we aim to discuss the major clinical trials investigating cardiac contractility modulation as a suitable therapy for patients with advanced heart failure.
Assuntos
Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Humanos , Qualidade de Vida , Volume Sistólico , Resultado do TratamentoRESUMO
Advances in therapies for hemophilia have led to an increased life expectancy for people with hemophilia. Limited data exist on the aging population of people with hemophilia who face additional challenges of age-related comorbidities. Efmoroctocog alfa (a recombinant factor VIII Fc fusion protein [herein referred to as rFVIIIFc]) and eftrenonacog alfa (a recombinant factor IX Fc fusion protein [rFIXFc]) are extended half-life factor replacements for hemophilia A and B, respectively, with demonstrated long-term safety and efficacy. The objective of this post hoc analysis was to describe long-term outcomes in participants 50+ years of age treated with rFVIIIFc or rFIXFc in pivotal Phase 3 trials and their extension studies: A-LONG (NCT01181128; n=21) and ASPIRE (NCT01454739; n=20 [95%]); B-LONG (NCT01027364; n=26) and B-YOND (NCT01425723; n=16 [62%]). Approximately half of participants (48%) with hemophilia A and 62% of participants with hemophilia B had a comorbidity at baseline. More than half of the participants were taking 1+ concomitant medication at baseline, with arthropathy and joint pain reported as the most common indications. Prophylaxis with rFVIIIFc or rFIXFc in individuals 50+ years of age with hemophilia A or B, respectively, resulted in low annualized bleed rates and improvements in joint health. Positive impacts on health-related quality of life were observed in individuals on either rFVIIIFc or rFIXFc prophylaxis. The results for the older subgroups were consistent with the overall study populations, demonstrating that prophylaxis with rFVIIIFc or rFIXFc provides long-term clinical benefits irrespective of age and presence of target joints in patients with severe hemophilia.
RESUMO
BACKGROUND: High-voltage pulses can cause hemolysis. OBJECTIVES: The authors evaluated the occurrence of hemoglobinuria after pulsed-field ablation (PFA) and its impact on renal function in patients with atrial fibrillation (AF). METHODS: A consecutive series of patients with AF undergoing PFA were included in this analysis. The initial patients who did not receive postablation hydration immediately after the procedure were classified as group 1 (n = 28), and the rest of the study patients who received planned fluid infusion (0.9% sodium chloride ≥2 L) after the procedure were categorized as group 2 (n = 75). RESULTS: Of the 28 patients in group 1, 21 (75%) experienced hemoglobinuria during the 24 hours after catheter ablation. The mean postablation serum creatinine (S-Cr) was significantly higher than the baseline value in those 21 patients (1.46 ± 0.28 mg/dL vs 0.86 ± 0.24 mg/dL, P < 0.001). Of those 21 patients, 4 (19%) had S-Cr. >2.5 mg/dL (mean: 2.95 ± 0.21 mg/dL). The mean number of PF applications was significantly higher in those 4 patients than in the other 17 patients experiencing hemoglobinuria (94.63 ± 3.20 vs 46.75 ± 9.10, P < 0.001). In group 2 patients, no significant changes in S-Cr were noted. The group 2 patients received significantly higher amounts of fluid infusion after catheter ablation than did those in group 1 (2,082.50 ± 258.08 mL vs 494.01 ± 71.65 mL, P < 0.001). In multivariable analysis, both hydration (R2 = 0.63, P < 0.01) and number of PFA applications (R2 = 0.33, P < 0.01) were independent predictors of postprocedure acute kidney injury. CONCLUSIONS: On the basis of our findings, both the number of PFA applications and postablation hydration were independent predictors of renal insult that could be prevented using planned fluid infusion immediately after the procedure.
Assuntos
Injúria Renal Aguda , Fibrilação Atrial , Ablação por Cateter , Hemoglobinúria , Humanos , Fibrilação Atrial/cirurgia , Masculino , Feminino , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Pessoa de Meia-Idade , Injúria Renal Aguda/prevenção & controle , Injúria Renal Aguda/etiologia , Idoso , Hemoglobinúria/etiologia , Hemoglobinúria/prevenção & controle , Creatinina/sangue , Estudos Retrospectivos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Hidratação/métodosRESUMO
The impairment of axonal transport by overexpression or hyperphosphorylation of tau is well documented for in vitro conditions; however, only a few studies on this phenomenon have been conducted in vivo, using invasive procedures, and with contradictory results. Here we used the non-invasive, Manganese-Enhanced Magnetic Resonance Imaging technique (MEMRI), to study for the first time a pure model of tauopathy, the JNPL3 transgenic mouse line, which overexpresses a mutated (P301L) form of the human tau protein. We show progressive impairment in neuronal transport as tauopathy advances. These findings are further supported by a significant correlation between the severity of the impairment in neuronal transport assessed by MEMRI, and the degree of abnormal tau assessed by histology. Unlike conventional techniques that focus on axonal transport measurement, MEMRI can provide a global analysis of neuronal transport, i.e. from dendrites to axons and at the macroscopic scale of fiber tracts. Neuronal transport impairment has been shown to be a key pathogenic process in Alzheimer's disease and numerous other neurodegenerative disorders. Hence, MEMRI provides a promising set of functional biomarkers to be used during preclinical trials to facilitate the selection of new drugs aimed at restoring neuronal transport in neurodegenerative diseases.
Assuntos
Cloretos/farmacocinética , Imageamento por Ressonância Magnética/métodos , Compostos de Manganês/farmacocinética , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Tauopatias/metabolismo , Tauopatias/patologia , Animais , Meios de Contraste/farmacocinética , Humanos , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo , Neurônios/patologia , Transmissão Sináptica , Proteínas tau/genéticaRESUMO
The frequencies of 6 different facultative pathogenic bacteria of the ESKAPE group (priority list WHO) and a total of 14 antibiotic resistance genes (ARGs) with different priorities for human medicine were quantified in wastewaters of poultry and pig slaughterhouses using molecular biological approaches. Raw sewage from poultry and pig slaughterhouses was found to be contaminated not only with facultative pathogenic bacteria but also with various categories of clinically relevant ARGs, including ARGs against the reserve antibiotics group. The concentration of the different gene targets decreased after on-site conventional biological or advanced oxidative wastewater treatments, but was not eliminated. Hence, the antimicrobial BlueLight (aBL) in combination with a porphyrin photo-sensitizer was studied with ESKAPE bacteria and real slaughterhouse wastewaters. The applied broad LED-based blue light (420-480 nm) resulted in groups of sensitive, intermediate, and non-sensitive ESKAPE bacteria. The killing effect of aBL was increased in the non-sensitive bacteria Klebsiella pneumoniae and Enterococcus faecium due to the addition of porphyrins in concentrations of 10-6 M. Diluted slaughterhouse raw wastewater was treated with broad spectrum aBL and in combination with porphyrin. Here, the presence of the photo-sensitizer enhanced the aBL biocidal impact.
Assuntos
Porfirinas , Águas Residuárias , Animais , Suínos , Humanos , Matadouros , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Antibacterianos/farmacologia , Genes Bacterianos , TecnologiaRESUMO
BACKGROUND: Hepatitis C is a diverse illness that causes significant death and morbidity. The hepatitis C virus infects hundreds of millions of individuals globally (HCV). More than 80% of those infected develop chronic infection; the remaining 10-20% recovers spontaneously through natural immunity. Acute hepatitis is only icteric in 20% of individuals and is seldom severe. METHODS: A pilot study was conducted at INOR hospital Abbottabad. Eleven hepatitis C positive and 10 hepatitis C negative participants were included in the study. RESULTS: A significant difference correlation was found between viral load and SWE quantification for fibrosis stage in Kilo-Pascal, r=0.904 (p-value=0.000
Assuntos
Hepatite C
, Humanos
, Projetos Piloto
, Carga Viral
, Hepacivirus
, Fibrose
RESUMO
INTRODUCTION: Although work to date in cystic fibrosis (CF) has elucidated frequencies and characteristics of adverse events, the accuracy of attribution of relatedness to study drug by investigators has not been assessed. We aimed to determine whether there was an association of attribution by group allocation in CF clinical trials. METHODS: We conducted a secondary analysis from 4 CF trials of all persons who experienced an AE. Our primary outcome was the odds of an AE related to active study drug and predictor of interest was the treatment allocation. We constructed a multivariable generalized estimating equation model allowing for repeated measures. RESULTS: A total of 785 subjects (47.5% female, mean age 12 years) had 11,974 AEs, of which 430 were serious. AE attribution was greater with receipt of active study drug as compared to placebo but did not reach statistical significance (OR 1.38, 95% CI 0.98-1.82). Significantly associated factors included female sex (OR 0.58, 95% 0.39-0.87), age (OR 1.24, 95% CI 1.06-1.46) and baseline lung function (per 10%, OR 1.16, 95% CI 1.05-1.28). CONCLUSION: In our large study, there was a non-significant but greater odds of AE attribution (a key element of clinical trial reporting) to active study drug based on assigned treatment to study drug or control which suggests that there is a trend in physicians to attribute blinded safety data to the active drug. Interestingly, females were less likely to have AE attribution to study drug and warrants further work in development and validation of monitoring guidelines and processes.