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1.
Clin Appl Thromb Hemost ; 28: 10760296211073277, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35000431

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious complication of acute pulmonary embolism (PE) which remains underdiagnosed. A better understanding of risk factors for CTEPH would improve our ability to predict which PE survivors are at risk. Several medical conditions-including malignancy, splenectomy, thyroid hormone supplementation, the presence of an intravascular device, inflammatory bowel disease, osteomyelitis, and non-O blood group-have been associated with increased risk of CTEPH, primarily in studies comparing patients with CTEPH to individuals with non-thrombotic conditions. Because many of these conditions increase thrombosis risk, it remains unclear whether their association with CTEPH reflects a general effect on thrombosis risk, or a specific effect on the risk of developing CTEPH as an outcome of thrombosis. We performed a case-control study comparing the frequencies of these conditions in patients with CTEPH versus patients with acute PE who did not develop CTEPH. The conditions studied were equally frequent in the CTEPH and PE cohorts, although there was a trend towards an increased frequency of splenectomy and non-O blood group among the CTEPH cohort. Thus, other than the possible exceptions of splenectomy and non-O blood group, the investigated medical conditions do not appear likely to increase the risk of CTEPH as an outcome of acute PE, and thus are unlikely to be useful in predicting CTEPH risk among PE survivors.


Assuntos
Hipertensão Pulmonar/etiologia , Embolia Pulmonar/epidemiologia , Medição de Risco/métodos , Doença Aguda , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Ecocardiografia , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/fisiopatologia , Incidência , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/complicações , Embolia Pulmonar/diagnóstico , Fatores de Risco , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia
2.
J Immunol Methods ; 495: 113049, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33819446

RESUMO

Documenting the importance of NK cell function as a biomarker for diseases and physiologic conditions including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), will require assays amenable to clinical implementation and standardization. Research studies typically perform NK functional assays on the day of sample collection. This pilot study was conducted to compare assay formats and specimen processing to identify those that are most tolerant of conditions required for shipping and amenable to standardization as shown by inter-assay and inter-laboratory correlation of results. We compared performance within and between assays that measure NK cell function using direct cytotoxicity [chromium-51 release (CRCA) or fluorescence (Flow Cytometry Cytotoxicity Assay, FCCA)] or an indirect surrogate marker (CD107a surface expression)]. Additional variables for within/between assay comparisons included time of testing (same day as specimen collection or next day within 24 h), specimen types [whole blood or isolated peripheral blood mononuclear cells (PBMCs)], and processing method (fresh or cryopreserved). Statistical measures included number of samples tested in assay conditions (n), medians (x͂), interquartile range (IQR), Pearson correlation coefficient (R2), and correlation p-value (p). Samples came from 3 clinics and included 31 participants. Same day testing was only available for the subset of participants enrolled from the site of the laboratory performing CRCA. Results from same day CRCA testing of whole blood were considered the gold standard [n = 10, x͂=10.0%, IQR = 7.2%], and correlated well with PBMCs isolated next day [n = 26, x͂= 15.6%, IQR = 13.1%] [R2 = 0.59, p = 0.03]. Next day CRCA results were compromised using whole blood or frozen PBMCs. Next day FCCA cytotoxicity in PBMC [n = 30, x͂=34.1%, IQR = 15.5%] correlated with same day CRCA PMBC [R2 = 0.8, p = 0.001] and next day CRCA PMBC [R2 = 0.5, p < 0.0001]. CD107a expression after induction by PMA and ionomycin did not correlate with other cytotoxicity measures. NK function can be measured in PBMCs isolated after overnight shipping/storage at ambient temperature and CRCA and FCCA results on this sample type are well correlated.


Assuntos
Coleta de Amostras Sanguíneas , Criopreservação , Citotoxicidade Imunológica , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/imunologia , Meios de Transporte , Biomarcadores/metabolismo , Estudos de Casos e Controles , Cromo/metabolismo , Citometria de Fluxo , Humanos , Imunofenotipagem , Células K562 , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/metabolismo , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Fenótipo , Projetos Piloto , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Temperatura , Fatores de Tempo , Estados Unidos
4.
Curr Protoc Cytom ; 92(1): e69, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32092227

RESUMO

Understanding how immune cells respond to external stimuli such as pathogens or drugs is a key component of biomedical research. Critical to the immune response are the expression of cell-surface receptors and the secretion of cytokines, which are tightly regulated by gene expression and protein synthesis. Previously, cytokine mRNA expression levels have been measured from bulk analysis of heterogeneous or sorted cell populations, and the correlation between cytokine mRNA expression and protein levels using these techniques can be highly variable. Flow cytometry is used to monitor changes in cell-surface and intracellular proteins, but some proteins such as cytokines may be transient and difficult to measure. Thus, a flow cytometry method that can simultaneously measure cytokine mRNA and protein levels in single cells is a very powerful tool. We defined a flow cytometry method that combines the conventional measurement of T cell surface proteins (CD45, CD3, CD4, CD8) and intracellular cytokines (IL-2, INF-γ) with fluorescent in situ hybridization and branched DNA technology for amplification and detection of IL-2 and INF-γ mRNA transcripts in activated T cells. This method has been applied to frozen peripheral mononuclear blood cells (PBMCs) and frozen blood samples, making it applicable to clinical trial specimens that require shipment to the test site. In CD4+ cells from activated PBMCs, the concordance between mRNA and protein levels was 41% for IL-2 and 21% for and INF-γ. In CD8+ cells from activated PBMCs, the concordance was 15% for IL-2 and 32% for INF-γ. © 2020 by John Wiley & Sons, Inc. Basic Protocol: Detection of IL-2 and IFN-γ mRNA and protein expression in frozen PBMCs Alternate Protocol: Detection of IL-2 and IFN-γ mRNA and protein expression in frozen blood.


Assuntos
Citocinas/genética , Citocinas/metabolismo , Citometria de Fluxo/métodos , Análise de Célula Única/métodos , Anticorpos/metabolismo , Permeabilidade da Membrana Celular , Análise de Dados , Humanos , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Coloração e Rotulagem , Linfócitos T/metabolismo
5.
Am J Hematol ; 94(12): 1335-1343, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31489983

RESUMO

The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) trials established routine transcranial Doppler ultrasound (TCD) screening, with indefinite chronic red cell transfusions (CRCT) for children with abnormal TCD as standard of care. Implementation failures and limitations to the STOP protocol may contribute to continued ischemic stroke occurrence. In the "Post-STOP" study, we sought to assess the impact of the STOP protocol on the incidence of ischemic stroke in a multicenter cohort of former STOP and/or STOP 2 trial participants. A central team abstracted data for 2851 (74%) of the 3835 children who took part in STOP and/or STOP 2. Data included TCD and neuroimaging results, treatment, laboratory data, and detailed clinical information pertaining to the stroke. Two stroke neurologists independently confirmed each stroke using pre-specified imaging and clinical criteria and came to consensus. Among the 2808 patients who were stroke-free at the start of Post-STOP with available follow-up, the incidence of first ischemic stroke was 0.24 per 100 patient-years (95% CI, 0.18, 0.31), with a mean (SD) duration of follow-up of 9.1 (3.4) [median 10.3, range (0-15.4)] years. Most (63%) strokes occurred in patients in whom the STOP protocol had not been properly implemented, either failure to screen appropriately with TCD (38%) or failure to transfuse adequately patients with abnormal TCD (25%). This study shows that substantial opportunities for ischemic stroke prevention remain by more complete implementation of the STOP Protocol.


Assuntos
Anemia Falciforme/complicações , Isquemia Encefálica/epidemiologia , Ultrassonografia Doppler Transcraniana , Adolescente , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/terapia , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Isquemia Encefálica/prevenção & controle , Criança , Pré-Escolar , Terapia Combinada , Angiografia por Tomografia Computadorizada , Transfusão de Eritrócitos , Feminino , Seguimentos , Humanos , Hidroxiureia/uso terapêutico , Incidência , Angiografia por Ressonância Magnética , Masculino , Estudos Multicêntricos como Assunto/métodos , Estudos Multicêntricos como Assunto/estatística & dados numéricos , Neuroimagem , Estudos Observacionais como Assunto/métodos , Estudos Observacionais como Assunto/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Fatores de Risco , Adulto Jovem
6.
Chest ; 155(2): 384-390, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30732691

RESUMO

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious sequela of pulmonary embolism (PE) and occurs in about 3% of acute PE survivors. Common inherited thrombophilias, including the Factor V Leiden mutation, are not associated with increased risk of CTEPH, even though they increase the risk for VTE. Whether other inherited genetic factors contribute to the risk of developing CTEPH remains unknown. Familial clustering of a disease can indicate inherited genetic risk for that disease. In this study, the Utah Population Database (UPDB), a unique genealogy resource, was used to assess whether CTEPH cases cluster in families. METHODS: Prevalent CTEPH patients in Utah were identified and were then matched to control subjects. Using the UPDB, the Genealogical Index of Familiality (a statistical measure of relatedness of individuals with a given phenotype) was calculated. The UPDB was also used to calculate the relative risk of CTEPH and VTE in the family members of patients with CTEPH. RESULTS: This study found that Utah patients with CTEPH are significantly more related than would be expected by chance, with both close and distant relationships identified. We also found that the relative risk of VTE was significantly increased among first-degree relatives of CTEPH probands. CONCLUSIONS: The study data suggest that heritable genetic factors influence an individual's risk of developing CTEPH, providing the strongest evidence to date for a genetic contribution to CTEPH risk. Although our data suggest that these inherited genetic factors likely also increase the risk for VTE, they are likely to be distinct from the common inherited thrombophilias.


Assuntos
Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/genética , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/genética , Idoso , Doença Crônica , Análise por Conglomerados , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Prevalência , Utah/epidemiologia
7.
Heart Fail Clin ; 14(3): 255-269, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29966625

RESUMO

This article provides an overview of pulmonary arterial hypertension (PAH), beginning with the initial pathologic recognition of pulmonary hypertension more than 100 years ago and progressing to the current diagnostic categorization of PAH. It reviews the epidemiology, pathophysiology, genetics, and modern treatment of PAH. The article discusses several important recent studies that have highlighted the importance of new management strategies, including serial risk assessment and combination pharmacotherapy.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Pulmonar/diagnóstico , Quimioterapia Combinada , Feminino , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Hipertensão Pulmonar/fisiopatologia , Masculino , Terapia de Alvo Molecular/métodos , Fatores de Risco , Taxa de Sobrevida
8.
Chest ; 151(4): 821-828, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27884767

RESUMO

BACKGROUND: Differentiating pulmonary venoocclusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) from idiopathic pulmonary arterial hypertension (IPAH) or heritable pulmonary arterial hypertension (HPAH) is important clinically. Mutations in eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) cause heritable PVOD and PCH, whereas mutations in other genes cause HPAH. The aim of this study was to describe the frequency of pathogenic EIF2AK4 mutations in patients diagnosed clinically with IPAH or HPAH. METHODS: Sanger sequencing and deletion/duplication analysis were performed to detect mutations in the bone morphogenetic protein receptor type II (BMPR2) gene in 81 patients diagnosed at 30 North American medical centers with IPAH (n = 72) or HPAH (n = 9). BMPR2 mutation-negative patients (n = 67) were sequenced for mutations in four other genes (ACVRL1, ENG, CAV1, and KCNK3) known to cause HPAH. Patients negative for mutations in all known PAH genes (n = 66) were then sequenced for mutations in EIF2AK4. We assessed the pathogenicity of EIF2AK4 mutations and reviewed clinical characteristics of patients with pathogenic EIF2AK4 mutations. RESULTS: Pathogenic BMPR2 mutations were identified in 8 of 72 (11.1%) patients with IPAH and 6 of 9 (66.7%) patients with HPAH. A novel homozygous EIF2AK4 mutation (c.257+4A>C) was identified in 1 of 9 (11.1%) patients diagnosed with HPAH. The novel EIF2AK4 mutation (c.257+4A>C) was homozygous in two sisters with severe pulmonary hypertension. None of the 72 patients with IPAH had biallelic EIF2AK4 mutations. CONCLUSIONS: Pathogenic biallelic EIF2AK4 mutations are rarely identified in patients diagnosed with HPAH. Identification of pathogenic biallelic EIF2AK4 mutations can aid clinicians in differentiating HPAH from heritable PVOD or PCH.


Assuntos
Hipertensão Pulmonar/genética , Mutação/genética , Proteínas Serina-Treonina Quinases/genética , Adulto , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte
9.
Am J Hematol ; 91(12): 1191-1194, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27623561

RESUMO

In children with Sickle Cell Disease, the combination of risk stratification with Transcranial Doppler Ultrasound (TCD) and selective chronic red cell transfusion (CRCT-the STOP Protocol) is one of the most effective stroke prevention strategies in medicine. How fully it is being implemented is unclear. Nineteen of 26 sites that conducted the two pivotal clinical trials (STOP and STOP II) participated in Post STOP, a comprehensive medical records review assessing protocol implementation in the 10-15 years since the trials ended. Professional abstractors identified medical records in the Post STOP era in 2851 (74%) of the 3,840 children who took part in STOP and/or STOP II, and documented TCD rescreening, maintenance of CRCT in those at risk, and stroke. Among 1,896 children eligible for TCD rescreening (target group), evidence of any rescreening was found in 1,090 (57%). There was wide site variation in TCD rescreening ranging from 18% to 91% of eligible children. Both younger age and having a conditional TCD during STOP/II were associated with a higher likelihood of having a TCD in Post STOP. Sixty eight new abnormal, high risk cases were identified. Despite clear evidence of benefit the STOP protocol is not fully implemented even at experienced sites. Site variation suggests that system improvements might remove barriers to implementation and result in even greater reduction of ischemic stroke in children with SCD. Am. J. Hematol. 91:1191-1194, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Acidente Vascular Cerebral/prevenção & controle , Ultrassonografia Doppler Transcraniana/métodos , Adolescente , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo , Criança , Pré-Escolar , Transfusão de Eritrócitos , Fidelidade a Diretrizes , Humanos , Programas de Rastreamento/métodos , Medição de Risco , Acidente Vascular Cerebral/diagnóstico por imagem
10.
Res Nurs Health ; 39(6): 438-448, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27545591

RESUMO

Treatment for acute ischemic stroke must be initiated within hours of stroke symptom onset, and the sooner it is administered, the better. In South Carolina, 76% of the population can access expert stroke care, and rural hospitals may provide specialized treatment using telemedicine, but many stroke sufferers seek care too late to achieve full benefit. Using a community-engaged approach in a southern rural community, we explored barriers and facilitators to early stroke care and implications for improvement. The Community-Engaged Assessment to facilitate Stroke Elimination (CEASE) study was guided by a community advisory group to ensure community centeredness and local relevance. In a qualitative descriptive study, eight focus groups were conducted including 52 individuals: recent stroke survivors, family members, emergency medical personnel, hospital emergency department staff, primary care providers, and community leaders. From analysis of focus group transcripts came six themes: lack of trust in healthcare system and providers; weak relationships fueled by poor communication; low health literacy; financial limitations related to health care; community-based education; and faith as a message of hope. A hierarchy model for improving early community-based stroke care was developed through consensus dialogue by community representatives and the research team. This model can be used to inform a community-partnered, stakeholder-informed intervention to improve stroke care in a rural southern community with the goal of improving stroke education, care, and outcome. © 2016 Wiley Periodicals, Inc.


Assuntos
Pesquisa Participativa Baseada na Comunidade/métodos , Intervenção Médica Precoce , Acessibilidade aos Serviços de Saúde/economia , Acidente Vascular Cerebral/terapia , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Letramento em Saúde , Humanos , Masculino , North Carolina , Educação de Pacientes como Assunto , Pesquisa Qualitativa , População Rural , Acidente Vascular Cerebral/diagnóstico , Telemedicina
12.
Can J Cardiol ; 31(4): 544-7, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25840103

RESUMO

Genetic testing is poised to play a greater role in the diagnosis and management of pulmonary arterial hypertension (PAH). Physicians who manage PAH should know the heritable PAH phenotypes, inheritance patterns, and responsible genes. They also should know indications, potential risks and benefits, and the issues surrounding genetic counselling and testing for patients with PAH.


Assuntos
Aconselhamento Genético/métodos , Testes Genéticos/métodos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/genética , Humanos , Fatores de Tempo
13.
J Immunol Methods ; 418: 1-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25662815

RESUMO

The objective of this manuscript is to present an approach for evaluating specimen stability for flow cytometric methods used during drug development. While this approach specifically addresses stability assessment for assays to be used in clinical trials with centralized testing facilities, the concepts can be applied to any stability assessment for flow cytometric methods. The proposed approach is implemented during assay development and optimization, and includes suggestions for designing a stability assessment plan, data evaluation and acceptance criteria. Given that no single solution will be applicable in all scenarios, this manuscript offers the reader a roadmap for stability assessment and is intended to guide the investigator during both the method development phase and in the experimental design of the validation plan.


Assuntos
Métodos Analíticos de Preparação de Amostras , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Descoberta de Drogas , Citometria de Fluxo , Humanos
14.
Chest ; 145(2): 231-236, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24135949

RESUMO

BACKGROUND: Pulmonary capillary hemangiomatosis (PCH) is a rare disease of capillary proliferation of unknown cause and with a high mortality. Families with multiple affected individuals with PCH suggest a heritable cause although the genetic etiology remains unknown. METHODS: We used exome sequencing to identify a candidate gene for PCH in a family with two affected brothers. We then screened 11 unrelated patients with familial (n = 1) or sporadic (n = 10) PCH for mutations. RESULTS: Using exome sequencing, we identified compound mutations in eukaryotic translation initiation factor 2 α kinase 4 (EIF2AK4) (formerly known as GCN2) in both affected brothers. Both parents and an unaffected sister were heterozygous carriers. In addition, we identified two EIF2AK4 mutations in each of two of 10 unrelated individuals with sporadic PCH. EIF2AK4 belongs to a family of kinases that regulate angiogenesis in response to cellular stress. CONCLUSIONS: Mutations in EIF2AK4 are likely to cause autosomal-recessive PCH in familial and some nonfamilial cases.


Assuntos
Pneumopatias/genética , Mutação/genética , Neovascularização Patológica/genética , Proteínas Serina-Treonina Quinases/genética , Doenças Vasculares/genética , Adolescente , Adulto , Capilares/patologia , Exoma/genética , Feminino , Heterozigoto , Humanos , Pneumopatias/patologia , Pneumopatias/cirurgia , Transplante de Pulmão , Masculino , Neovascularização Patológica/patologia , Neovascularização Patológica/cirurgia , Pais , Linhagem , Irmãos , Doenças Vasculares/patologia , Doenças Vasculares/cirurgia
15.
Am J Med ; 126(1): 36-42, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23177546

RESUMO

BACKGROUND: Computed tomography (CT) pulmonary angiography use has increased dramatically, raising concerns for patient safety. Adherence to recommendations and guidelines may protect patients. We measured adherence to the recommendations of Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED II) investigators for evaluation of suspected pulmonary embolism and the rate of potential false-positive pulmonary embolism diagnoses when recommendations of PIOPED II investigators were not followed. METHODS: We used a structured record review to identify 3500 consecutive CT pulmonary angiograms performed to investigate suspected pulmonary embolism in 2 urban emergency departments, calculating the revised Geneva score (RGS) to classify patients as "pulmonary embolism unlikely" (RGS≤10) or "pulmonary embolism likely" (RGS>10). CT pulmonary angiograms were concordant with PIOPED II investigator recommendations if pulmonary embolism was likely or pulmonary embolism was unlikely and a highly sensitive D-dimer test result was positive. We independently reviewed 482 CT pulmonary angiograms to measure the rate of potential false-positive pulmonary embolism diagnoses. RESULTS: A total of 1592 of 3500 CT pulmonary angiograms (45.5%) followed the recommendations of PIOPED II investigators. The remaining 1908 CT pulmonary angiograms were performed on patients with an RGS≤10 without a D-dimer test (n=1588) or after a negative D-dimer test result (n=320). The overall rate of pulmonary embolism was 9.7%. Potential false-positive diagnoses of pulmonary embolism occurred in 2 of 3 patients with an RGS≤10 and a negative D-dimer test result. CONCLUSIONS: Nonadherence to recommendations for CT pulmonary angiography is common and exposes patients to increased risks, including potential false-positive diagnoses of pulmonary embolism.


Assuntos
Fidelidade a Diretrizes/estatística & dados numéricos , Embolia Pulmonar/diagnóstico por imagem , Adulto , Idoso , Angiografia , Reações Falso-Positivas , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Tomografia Computadorizada por Raios X
16.
Chest ; 140(1): 19-26, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21393391

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder. Despite the emergence of effective therapy, PAH is commonly at an advanced stage when recognized. Factors associated with a prolonged symptomatic period before the recognition of PAH have not been fully evaluated. METHODS: The Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL Registry) enrolled 2,967 US adult patients with PAH from March 2006 to September 2007. Patients were considered to have delayed disease recognition if > 2 years elapsed between symptom onset and the patient receiving a PAH diagnosis, starting on PAH-specific therapy, or receiving a diagnosis by right-sided heart catheterization. RESULTS: In 21.1% of patients, symptoms were experienced for > 2 years before PAH was recognized. Patients with onset of PAH symptoms before age 36 years showed the highest likelihood of delayed disease recognition (OR, 3.07; 95% CI, 2.03-4.66). History of obstructive airways disease (OR, 1.93; 95% CI, 1.5-2.47) and sleep apnea (OR, 1.72; 95% CI, 1.33-2.22) were independently associated with delayed PAH recognition. Six-minute walk distance < 250 m (OR, 1.91; 95% CI, 1.16-3.13), right atrial pressure < 10 mm Hg (OR, 1.77; 95% CI, 1.26-2.48), and pulmonary vascular resistance < 10 Wood units (OR, 1.28; 95% CI, 1.02-1.60) were also associated with delayed disease recognition, but sex, race/ethnicity, and geographic region showed no association. CONCLUSIONS: One in five patients in the REVEAL Registry who were diagnosed with PAH reported symptoms for > 2 years before their disease was recognized. Younger individuals and patients with histories of common respiratory disorders were most likely to experience delayed PAH recognition. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00370214; URL: www.clinicaltrials.gov.


Assuntos
Obstrução das Vias Respiratórias/complicações , Cateterismo Cardíaco/métodos , Diagnóstico Precoce , Hipertensão Pulmonar/diagnóstico , Sistema de Registros , Síndromes da Apneia do Sono/complicações , Adulto , Idoso , Obstrução das Vias Respiratórias/diagnóstico , Diagnóstico Diferencial , Progressão da Doença , Feminino , Seguimentos , Humanos , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Pressão Propulsora Pulmonar , Estudos Retrospectivos , Síndromes da Apneia do Sono/diagnóstico , Fatores de Tempo , Estados Unidos/epidemiologia
17.
J Immunol Methods ; 363(2): 104-19, 2011 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-20655313

RESUMO

Flow cytometry is a powerful and flexible analytical tool used during all stages of drug development. While substantial effort is invested in development and validation of analytical methods, instrument validation is often neglected. Flow cytometers are evolving at a pace that surpasses the protracted timeline of drug discovery and development. Therefore, it becomes fundamentally important to the success of the study to document the validated state of the flow cytometer and verify data integrity at the time of study conduct. It is important to bear in mind that validation strategies are critical components of the entire process involved in bringing new therapeutic options to the medical community; drugs which eventually manifest as successful new treatments for those individuals afflicted with disease. Formal industry guidance is provided through Good Laboratory Practices [GLP], which require validation of all computerized systems and equipment used to support pre-clinical studies for regulatory submissions. Key elements of instrument validation processes have been delineated through guidance documents published by regulatory agencies and industry working groups to support the rigorous compliance needs of GLP. However, most testing to support drug development is conducted in less strict regulatory environments. Such comprehensive validation efforts may not be appropriate for laboratories supporting early discovery or basic research, however, laboratories involved in regulated stages of development, such as pre-clinical and clinical phases, should consider these recommendations. This paper presents a consensus methodological approach that the authors have used successfully to ensure data integrity in flow cytometric studies conducted during drug development.


Assuntos
Descoberta de Drogas/normas , Citometria de Fluxo/normas , Descoberta de Drogas/instrumentação , Citometria de Fluxo/instrumentação , Citometria de Fluxo/métodos , Reprodutibilidade dos Testes , Pesquisa Translacional Biomédica
18.
Clin Chest Med ; 31(4): 641-57, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21047573

RESUMO

The diagnosis of venous thromboembolism (VTE) cannot be confirmed or excluded by the medical history and physical examination alone. Objective testing is required in all cases of clinically suspected VTE; for most patients, this includes imaging modalities such as compression ultrasonography, ventilation-perfusion lung scintigraphy, or computed tomography pulmonary angiography (CTPA). Conventional pulmonary arteriography remains useful when CTPA is nondiagnostic or when an intervention such as catheter embolectomy is planned. Although CTPA is important in the evaluation of suspected VTE, ultimately the clinician must balance the risks against the benefits of CTPA for individual patients. Bedside echocardiography may be most appropriate for patients with hypotension or shock and suspected pulmonary embolism.


Assuntos
Embolia Pulmonar/diagnóstico por imagem , Tromboembolia Venosa/diagnóstico por imagem , Trombose Venosa/diagnóstico por imagem , Angiografia , Meios de Contraste , Ecocardiografia , Humanos , Angiografia por Ressonância Magnética , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X
19.
J Natl Med Assoc ; 102(9): 842-3, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20922931

RESUMO

In 1967, the American Board of Pediatrics and the American Board of Internal Medicine uniformly recognized the 4-year combined medicine and pediatrics training program. Since that time, the number of combined internal medicine and pediatrics programs has increased. Today, there are more than 78 combined residency programs with more than 354 first-year residency positions throughout the United States. Medicine/pediatrics residency programs give the resident the opportunity to rotate 24 months in each specialty. Graduates of combined medicine/pediatrics residency programs have several career options available to them. In 2007, a total of 55% of medicine/pediatrics residents went into primary care practice, 18% went into subspecialty training, 17% went into hospital medicine, and 10% chose other careers.


Assuntos
Medicina Interna/educação , Internato e Residência/organização & administração , Pediatria/educação , Medicina de Família e Comunidade/educação , Humanos , Estados Unidos
20.
Chest ; 137(6 Suppl): 85S-94S, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20522584

RESUMO

Pulmonary hypertension (PH) affects > 25 million individuals worldwide and causes premature disability and death for many. The diagnosis and treatment of PH have advanced dramatically through the development of a clearly defined diagnostic classification, an evidence-based treatment algorithm for adults with pulmonary arterial hypertension using life-saving medications, and life-saving surgical procedures. However, worldwide education and training of physicians has lagged behind advances in the management of PH. Expertise in the diagnosis and management of PH is uncommon, even though physicians receive training on PH during their graduate and postgraduate education. Advances in worldwide physician education and training in PH will require substantial organization and work. Organizations working in this field will need to work collaboratively to maximize funding for education and to optimize the achievement of educational goals. Political, economic, and cultural barriers must be identified and overcome as part of any strategic plan. Global education should include training objectives for generalist, non-PH specialist, and PH specialist physicians.


Assuntos
Educação Médica Continuada , Hipertensão Pulmonar , Competência Clínica , Saúde Global , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/fisiopatologia , Modelos Educacionais
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