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1.
Am J Hematol ; 95(2): 156-166, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31721282

RESUMO

Myeloproliferative Neoplasms (MPN) course can be complicated by thrombosis involving unusual sites as the splanchnic veins (SVT). Their management is challenging, given their composite vascular risk. We performed a retrospective, cohort study in the framework of the International Working Group for MPN Research and Treatment (IWG-MRT), and AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM). A total of 518 MPN-SVT cases were collected and compared with 1628 unselected, control MPN population, matched for disease subtype. Those with MPN-SVT were younger (median 44 years) and enriched in females compared to controls; PV (37.1%) and ET (34.4%) were the most frequent diagnoses. JAK2V617F mutation was highly prevalent (90.2%), and 38.6% of cases had an additional hypercoagulable disorder. SVT recurrence rate was 1.6 per 100 patient-years. Vitamin K-antagonists (VKA) halved the incidence of recurrence (OR 0.48), unlike cytoreduction (OR 0.96), and were not associated with overall or gastrointestinal bleeding in multivariable analysis. Esophageal varices were the only independent predictor for major bleeding (OR 17.4). Among MPN-SVT, risk of subsequent vascular events was skewed towards venous thromboses compared to controls. However, MPN-SVT clinical course was overall benign: SVT were enriched in PMF with lower IPSS, resulting in significantly longer survival than controls; survival was not affected in PV and slightly reduced in ET. MPN-U with SVT (n = 55) showed a particularly indolent phenotype, with no signs of disease evolution. In the to-date largest, contemporary cohort of MPN-SVT, VKA were confirmed effective in preventing recurrence, unlike cytoreduction, and safe; the major risk factor for bleeding was esophageal varices that therefore represent a major therapeutic target.

2.
Intern Emerg Med ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776841

RESUMO

In the original publication, part of the conflict of statement was incorrectly published as "Dr. Bikdeli reports that he was approached by lawyers on behalf of plaintiffs in litigation related to IVC filters". The correct statement should read as "Dr. Bikdeli reports that he is a consulting expert (on behalf of the plaintiff) for litigation related to a specific type of IVC filters".

3.
Leuk Lymphoma ; 60(12): 2922-2926, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31167584

RESUMO

The reported prevalence of hypercalcemia at diagnosis in non-Hodgkin-lymphoma ranges between 1.3% and 7.4%. These studies included all patients, regardless of lymphoma subtype. We performed a retrospective case-control study to determine the prevalence of hypercalcemia at time of diagnosis in patients with diffuse large B-cell lymphoma (DLBCL). Among 250 newly diagnosed patients, 46 (18%) had hypercalcemia. When compared with age-sex matched patients and normal calcium levels, those with hypercalcemia had higher levels of LDH, lower levels of albumin and more advanced stage. These differences were translated to shorter progression-free-survival and overall survival, but only in patients with hypercalcemia and low levels of parathyroid hormone (PTH). These findings suggest that in newly diagnosed patients with DLBCL, hypercalcemia is more frequent than previously appreciated. Furthermore, lymphoma-related but not primary hyperparathyroidism-related hypercalcemia is associated with adverse prognostic factors and adverse clinical outcomes in DLBCL. Hence, PTH should be obtained in patients with DLBCL and hypercalcemia at diagnosis.

6.
Intern Emerg Med ; 14(7): 1101-1112, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31054013

RESUMO

The association between inferior vena cava filter (IVC) use and outcome in patients presenting with major bleeding during anticoagulation for venous thromboembolism (VTE) has not been thoroughly investigated. We used the RIETE registry to compare the 30-day outcomes (death, major re-bleeding or VTE recurrences) in VTE patients who bled during the first 3 months of therapy, regarding the insertion of an IVC filter. A propensity score matched (PSM) analysis was performed to adjust for potential confounders. From January 2001 to September 2016, 1065 VTE patients had major bleeding during the first 3 months of anticoagulation (gastrointestinal 370; intracranial 124). Of these, 122 patients (11%) received an IVC filter. Patients receiving a filter restarted anticoagulation later (median, 4 vs. 2 days) and at lower doses (95 ± 52 IU/kg/day vs. 104 ± 55 of low-molecular-weight heparin) than those not receiving a filter. During the first 30 days after bleeding (after excluding 246 patients who died within the first 24 h), 283 patients (27%) died, 63 (5.9%) had non-fatal re-bleeding and 19 (1.8%) had recurrent pulmonary embolism (PE). In PSM analysis, patients receiving an IVC filter (n = 122) had a lower risk for all-cause death (HR 0.49; 95% CI 0.31-0.77) or fatal bleeding (HR 0.16; 95% CI 0.07-0.49) and a similar risk for re-bleeding (HR 0.55; 95% CI 0.23-1.40) or PE recurrences (HR 1.57; 95% CI 0.38-6.36) than those not receiving a filter (n = 429). In VTE patients experiencing major bleeding during the first 3 months, use of an IVC filter was associated with reduced mortality rates.Clinical Trial Registration NCT02832245.

7.
Heart ; 105(19): 1487-1492, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30971403

RESUMO

OBJECTIVE: Although direct oral anticoagulants (DOAC) are the recommended antithrombotic therapy for patients with non-valvular atrial fibrillation (NVAF), anticoagulation in patients with NVAF is still inadequate. The effect of withholding DOAC therapy on patient survival is unknown. Therefore, our objective was to compare all-cause mortality rates between DOAC-treated patients with NVAF and similar patients receiving no anticoagulation. METHODS: We performed a retrospective cohort study analysing Clalit Health Services' extensive electronic database, regarding all newly diagnosed, anticoagulant-naïve patients with NVAF who were eligible for DOAC therapy from 1 January 2011 to 31 December 2016. Patients who received DOAC therapy were matched by propensity scoring to patients receiving no anticoagulation. The primary outcome was all-cause mortality. Final patient follow-up date was 15 May 2017. RESULTS: 18 901 eligible patients were identified. 8298 received treatment with a DOAC and 10 603 received no anticoagulation therapy. Of those, 5657 patients who received DOAC therapy were matched with 5657 patients who did not receive any anticoagulant. Death occurred in 715 patients in the DOAC-treated group (7.6% per year) and in 2075 patients in the non-anticoagulated patient group (11.1% per year). DOAC therapy was associated with significantly lower risk for all-cause mortality (HR=0.69, 95% CI 0.63 to 0.75, p<0.001). The benefit of DOAC therapy was demonstrated across all subgroups analysed. CONCLUSIONS: In this cohort of newly diagnosed patients with NVAF, DOAC therapy was associated with a significantly lower risk of death compared with no oral anticoagulation. Our findings provide further evidence for the importance of providing DOAC anticoagulation in patients with NVAF.

8.
Eur J Haematol ; 102(6): 504-508, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30941804

RESUMO

OBJECTIVE: Approximately 10% of Philadelphia (Ph)-negative myeloproliferative neoplasms (NPM) are diagnosed at young adulthood. We aim to define the features of this group. METHODS: A multicenter retrospective study, including patients 18-45 years of age, diagnosed with Ph-negative MPN between 1985 and 2017. RESULTS: One hundred nine patients were included, 37 with polycythemia vera (34%), 54 with essential thrombocytosis (50%), 15 with primary myelofibrosis (PMF) (14%), and 3 with MPN unclassifiable (3%). Median age was 33 years and 62 (57%) were females. During a median follow-up of 8 years, 39 patients (37%) had at least one thrombotic event. 30/39 of events were venous (77%), 23/30 of which were splanchnic (77%). In 14/39 (36%), thrombosis preceded MPN diagnosis. In a multivariable analysis, only splenomegaly predicted for thrombosis (HR 5.6, CI: 1.4-22). The 10-year risk for secondary myelofibrosis was similar for ET and PV (0.13 vs 0.19, P = 0.51). The 10-year risk for leukemic transformation or mortality was significantly higher for PMF (0.3, P = 0.04). CONCLUSIONS: The risks of mortality and of progression to MF/leukemia in young adults are similar to older population. Thrombotic events are frequently a presenting sign with a high incidence of venous, in particular splanchnic, events.


Assuntos
Transtornos Mieloproliferativos/diagnóstico , Adulto , Biomarcadores , Transformação Celular Neoplásica , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/terapia , Cromossomo Filadélfia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Avaliação de Sintomas , Trombose/diagnóstico , Trombose/etiologia , Adulto Jovem
9.
Artigo em Inglês | MEDLINE | ID: mdl-30814976

RESUMO

Thyroid hormones take major part in normal growth, development and metabolism. Over a century of research has supported a relationship between thyroid hormones and the pathophysiology of various cancer types. In vitro studies as well as research in animal models demonstrated an effect of the thyroid hormones T3 and T4 on cancer proliferation, apoptosis, invasiveness and angiogenesis. Thyroid hormones mediate their effects on the cancer cell through several non-genomic pathways including activation of the plasma membrane receptor integrin αvß3. Furthermore, cancer development and progression are affected by dysregulation of local bioavailability of thyroid hormones. Case-control and population-based studies provide conflicting results regarding the association between thyroid hormones and cancer. However, a large body of evidence suggests that subclinical and clinical hyperthyroidism increase the risk of several solid malignancies while hypothyroidism may reduce aggressiveness or delay the onset of cancer. Additional support is provided from studies in which dysregulation of the thyroid hormone axis secondary to cancer treatment or thyroid hormone supplementation was shown to affect cancer outcomes. Recent preclinical and clinical studies in various cancer types have further shown promising outcomes following chemical reduction of thyroid hormones or inhibition or their binding to the integrin receptor. This review provides a comprehensive overview of the preclinical and clinical research conducted so far.

10.
Harefuah ; 158(3): 200-204, 2019 Mar.
Artigo em Hebraico | MEDLINE | ID: mdl-30916511

RESUMO

INTRODUCTION: The direct oral anticoagulants (DOACs) are a class of drugs used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation and for prevention and treatment of venous thrombo-embolism. They are as effective and are safer than the vitamin K antagonists that were the oral drugs previously used for this purpose. The DOACs are convenient to use because of their fixed dose-response relationship which makes routine monitoring of drug levels unnecessary. Further, they have no food interactions and relatively few drug interactions. A number of practical considerations related to the routine clinical use of the DOACs have become apparent. These include choosing the appropriate drug and importantly dose-based on patient characteristics, managing the use of DOACs peri-operatively and the appropriate management of the acutely bleeding DOAC-treated patient. Recent controlled and observational studies provide guidance for dealing with these clinical situations thus enhancing the efficacy and safety of DOAC treatment in routine clinical practice.


Assuntos
Anticoagulantes , Fibrilação Atrial , Acidente Vascular Cerebral , Administração Oral , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Hemorragia/induzido quimicamente , Humanos , Acidente Vascular Cerebral/prevenção & controle
11.
Am J Med ; 132(7): 847-855.e3, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30776320

RESUMO

BACKGROUND: Direct oral anticoagulants (DOACs) reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation but may result in serious bleeding complications. Off-label dose-reduced use of DOACs to mitigate bleeding is common in routine clinical practice although data about its consequences on patient outcomes are limited. Therefore, our objective was to evaluate the effectiveness and safety of off-label dose-reduced vs per-label standard-dose DOAC treatment. METHODS: The study cohort included newly diagnosed patients with nonvalvular atrial fibrillation that had initiated DOAC therapy between 2011 and 2017 in Clalit Health Services (Tel Aviv, Israel). Effectiveness was defined as the composite outcome of all-cause mortality, stroke, or myocardial infarction. The safety outcome was defined as bleeding events requiring hospitalization. Patients were followed until March 30, 2018 or until occurrence of an outcome event. Hazard ratios (HR) were adjusted for 21 variables, including comorbidities, concomitant medications, and socioeconomic factors, using multivariate regression. RESULTS: A total of 8425 patients met the study criteria; 5140 (61%) patients were treated with DOACs at per-label dosing and 3285 (39%) patients were treated with off-label dose-reduced DOAC. Off-label dose-reduced treatment was associated with a higher rate of the composite effectiveness outcome: adjusted HR 1.57 (95% confidence interval, 1.34-1.83; P < .001) and a higher rate of bleeding: adjusted HR 1.63 (95% confidence interval, 1.14-2.34; P = .008). CONCLUSIONS: Almost 4 of 10 patients were treated with off-label dose-reduced DOAC, which was associated with reduced effectiveness without a safety benefit. Compliance with per-label dosage may significantly improve outcomes of this population.


Assuntos
Anticoagulantes/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Uso Off-Label/estatística & dados numéricos , Acidente Vascular Cerebral/prevenção & controle , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Fibrilação Atrial/mortalidade , Feminino , Humanos , Masculino , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento
12.
Transfusion ; 59(3): 972-980, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30549289

RESUMO

BACKGROUND: Wrong blood in tube (WBIT) errors are a preventable cause of ABO-mismatched RBC transfusions. Electronic patient identification systems (e.g., scanning a patient's wristband barcode before pretransfusion sample collection) are thought to reduce WBIT errors, but the effectiveness of these systems is unclear. STUDY DESIGN AND METHODS: Part 1: Using retrospective data, we compared pretransfusion sample WBIT rates at hospitals using manual patient identification (n = 16 sites; >1.6 million samples) with WBIT rates at hospitals using electronic patient identification for some or all sample collections (n = 4 sites; >0.5 million samples). Also, we compared WBIT rates after implementation of electronic patient identification with preimplementation WBIT rates. Causes and frequencies of WBIT errors were evaluated at each site. Part 2: Transfusion service laboratories (n = 18) prospectively typed mislabeled (rejected) samples (n = 2844) to determine WBIT rates among samples with minor labeling errors. RESULTS: Part 1: The overall unadjusted WBIT rate at sites using manual patient identification was 1:10,110 versus 1:35,806 for sites using electronic identification (p < 0.0001). Correcting for repeat samples and silent WBIT errors yielded overall adjusted WBIT rates of 1:3046 for sites using manual identification and 1:14,606 for sites using electronic identification (p < 0.0001), with wide variation among individual sites. Part 2: The unadjusted WBIT rate among mislabeled (rejected) samples was 1:71 (adjusted WBIT rate, 1:28). CONCLUSION: In this study, using electronic patient identification at the time of pretransfusion sample collection was associated with approximately fivefold fewer WBIT errors compared with using manual patient identification. WBIT rates were high among mislabeled (rejected) samples, confirming that rejecting samples with even minor labeling errors helps mitigate the risk of ABO-incompatible transfusions.


Assuntos
Registros Eletrônicos de Saúde/normas , Erros Médicos/estatística & dados numéricos , Bancos de Sangue/estatística & dados numéricos , Coleta de Amostras Sanguíneas/normas , Humanos , Estudos Retrospectivos
14.
Cartilage ; 10(1): 53-60, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29308659

RESUMO

OBJECTIVE: To test whether patients with spontaneous osteonecrosis of the knee (SONK) are characterized by abnormal levels of thrombophilia-associated factors. DESIGN: Twenty-five patients with SONK were recruited. Inclusion criteria were (1) age >40 years, (2) acute onset knee pain not precipitated by trauma, and (3) MRI findings consistent with SONK. Exclusion criteria were (1) history of cancer and chemotherapy and (2) factors associated with secondary osteonecrosis. Blood tests included 13 thrombophilia-associated factors that were either heritable mutations or acquired factors. Descriptive statistics included medians, ranges, means, and standard deviations. Mann-Whitney test was used to compare thrombophilia-associated factor levels between the sexes. Spearman's rank test was used to test correlations between smoking status and each thrombophilia-associated factor. Level of significance was set at 0.05. RESULTS: Median patient age was 62 years (range, 44-77 years). There were 16 (64%) men. Thirteen (52%) patients had thrombophilia-associated factor abnormalities of which 9 were elevated fibrinogen but this was less than 1 standard deviation above norm threshold. Other findings were 3 patients with marginally decreased antithrombin below norm threshold, low protein S Ag in only 1 patient, and factor V Leiden mutation heterozygosity in 2 patients, which was not higher than normal population prevalence. Thrombophilia-associated factors neither differed between sexes ( P = nonsignificant) nor correlated with smoking status ( P = nonsignificant). CONCLUSION: Thrombophilia-associated factor abnormalities in patients with SONK were minimal. Therefore, clinical workup and treatment strategy in this disease should focus on addressing alternative etiologies leading to abnormal subchondral bone metabolism with focal osteopenia.


Assuntos
Fator V/análise , Osteonecrose/sangue , Trombofilia/complicações , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteonecrose/etiologia , Osteonecrose/patologia , Fatores de Risco , Trombofilia/sangue , Trombofilia/patologia
15.
J Am Heart Assoc ; 7(17): e009042, 2018 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-30371152

RESUMO

Background Transthoracic echocardiography ( TTE ) is often considered for risk stratification of patients with acute pulmonary embolism ( PE ). We sought to determine the contemporary utilization of early TTE (within 72 hours of PE diagnosis) and explored the association between TTE findings and PE -related mortality. Methods and Results Data from the RIETE (Registro Informatizado Enfermedad TromboEmbolica) registry, a multicenter registry of consecutive patients with acute PE , were used (2001-July 2017). We used a generalized linear mixed model to determine predictors of early TTE performance. Moreover, the association between 3 TTE variables (right atrial enlargement, right ventricular hypokinesis, and presence of right heart thrombi) and 30-day PE -related mortality was assessed in generalized linear mixed models adjusted for PE severity index, and other comorbidities. Among 35 935 enrollees with acute PE , 15 375 (42.8%) underwent early TTE . There was an increase in early TTE utilization rate over time ( P<0.001 for trend). Younger age, female sex, enrollment in countries other than Spain, history of coronary disease, heart failure, atrial fibrillation, tachycardia, and hypotension were the main predictors of early TTE ( P<0.01 for all). In multivariable analyses, right atrial enlargement (adjusted odds ratio: 3.74; 95% confidence interval, 2.10-6.66), right ventricular hypokinesis (adjusted odds ratio: 3.11, 95% confidence interval: 1.85-5.21) and right heart thrombi (adjusted odds ratio: 4.39, 95% confidence interval, 1.99-9.71) were associated with increased odds for PE -related mortality. Conclusions Early TTE is commonly performed for acute PE and utilization rates have increased over time. Right atrial enlargement, right ventricular hypokinesis, and right heart thrombi are predictive of worse outcomes. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 02832245.


Assuntos
Ecocardiografia/estatística & dados numéricos , Átrios do Coração/diagnóstico por imagem , Cardiopatias/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagem , Trombose/diagnóstico por imagem , Disfunção Ventricular Direita/diagnóstico por imagem , Doença Aguda , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/epidemiologia , Doença das Coronárias/epidemiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Humanos , Hipotensão/epidemiologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/mortalidade , Medição de Risco , Fatores Sexuais , Taquicardia/epidemiologia
16.
Clin Lymphoma Myeloma Leuk ; 18(9): e351-e362, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30122203

RESUMO

BACKGROUND: There are inconsistencies in reports on correlates for nonadherence (NA) to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). The diagnostic accuracy of subjective adherence measures using electronic monitoring (EM) as the reference standard is yet to be determined. This study aimed to evaluate correlates of TKI NA using EM and test the diagnostic accuracy of subjective adherence measures. PATIENTS AND METHODS: CML patients receiving a TKI for any duration were enrolled at 4 hematology institutes, and adherence was measured for 4 months. EM adherence was the reference adherence measure, expressed as the percentage of days with the drug taken as prescribed. Subjective adherence was measured using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS) self-report and clinician-reported visual analog scale (VAS) at 2 time points. Baseline theory-derived correlates of NA were identified using single and multiple regression analysis. The diagnostic accuracy of BAASIS and clinician-reported VAS was tested against an exploratory EM NA cutoff of < 95%. RESULTS: The median EM adherence (n = 55) was 97.5% (range, 48-100%), while the 25th percentile was 92.1%. Lack of membership in a CML patient support group, living alone, and third-line treatment were associated with EM NA on multiple regression analysis. The BAASIS self-report (n = 94) had a sensitivity of 67% and a specificity of 71% for diagnosing NA, while clinician-reported VAS (n = 89) had a sensitivity of 78% and specificity of 42%. CONCLUSION: A quarter of patients had potentially clinically meaningful NA. These NA correlates and the BAASIS provide a basis for identifying nonadherent patients who can be targeted by interventions.


Assuntos
Implementação de Plano de Saúde , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Feminino , Seguimentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Prognóstico , Inquéritos e Questionários
18.
Clin Lymphoma Myeloma Leuk ; 18(11): e449-e461, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30030034

RESUMO

BACKGROUND: Nonadherence to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has been associated with inferior outcomes. Scarce evidence exists on the effectiveness of adherence-enhancing interventions. The present pilot study evaluated the feasibility and effectiveness of an intervention to improve TKI adherence in adult CML patients. PATIENTS AND METHODS: Using a quasi-experimental pre-post intervention design, we included a convenience sample of 58 CML patients (median age, 60.5 years; interquartile range, 19) receiving TKI treatment in 4 hematology institutes in Israel (median previous treatment duration, 34 months; interquartile range, 60). Of the 58 patients, 36 (62%) were receiving first-line treatment. TKI adherence was assessed using electronic monitoring for 7 months (4 months for the baseline assessment and for 3 months after the intervention) and defined as the percentage of days with dosing taken as prescribed. The multilevel intervention combined training of health care workers and multiple behavioral change techniques (eg, motivational interviewing, feedback on electronic monitoring printouts, behavioral change techniques tailored to reasons for nonadherence). The baseline and postintervention adherence were compared using generalized estimating equation models. RESULTS: The median baseline electronically monitored adherence (n = 55) was 97.5% (range, 48%-100%). The odds of taking the drug daily as prescribed were 58% greater after intervention (odds ratio, 1.58; 95% confidence interval [CI], 1.16-2.15). Adherence improved by only 1.5% overall (95% CI, 0.1%-2.8%) but by 8.5% (i.e. from 71.2% average adherence before intervention, to 79.6% after; P = .04) in a subgroup of 10 nonadherent patients (baseline adherence < 90%). CONCLUSION: TKI adherence improved with our pilot intervention, mainly in patients with suboptimal baseline adherence.


Assuntos
Intervenção Médica Precoce , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Feminino , Seguimentos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados não Aleatórios como Assunto , Projetos Piloto , Prognóstico
19.
Eur J Haematol ; 101(3): 297-304, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29786897

RESUMO

BACKGROUND: Most patients with anemia are diagnosed through clinical phenotype and basic laboratory testing. Nonetheless, in cases of rare congenital anemias, some patients remain undiagnosed despite undergoing an exhaustive workup. Genetic testing is complicated by the large number of genes involved in rare anemias and the similarities in the clinical presentation of the different syndromes. OBJECTIVE: We aimed to enhance the diagnosis of patients with congenital anemias by using targeted next-generation sequencing. METHODS: Genetic diagnosis was performed by gene capture followed by next-generation sequencing of 76 genes known to cause anemia syndromes. RESULTS: Genetic diagnosis was achieved in 13 out of 21 patients (62%). Six patients were diagnosed with pyruvate kinase deficiency, 4 with dehydrated hereditary stomatocytosis, 2 with sideroblastic anemia, and 1 with CDA type IV. Eight novel mutations were found. In 7 patients, the genetic diagnosis differed from the pretest presumed diagnosis. The mean lag time from presentation to diagnosis was over 13 years. CONCLUSIONS: Targeted next-generation sequencing led to an accurate diagnosis in over 60% of patients with rare anemias. These patients do not need further diagnostic workup. Earlier incorporation of this method into the workup of patients with congenital anemia may improve patients' care and enable genetic counseling.


Assuntos
Anemia/congênito , Anemia/diagnóstico , Estudos de Associação Genética , Adolescente , Adulto , Anemia/sangue , Anemia/terapia , Anemia Diseritropoética Congênita/diagnóstico , Anemia Diseritropoética Congênita/genética , Anemia Diseritropoética Congênita/terapia , Anemia Hemolítica Congênita/diagnóstico , Anemia Hemolítica Congênita/genética , Anemia Hemolítica Congênita não Esferocítica/diagnóstico , Anemia Hemolítica Congênita não Esferocítica/genética , Anemia Sideroblástica/diagnóstico , Anemia Sideroblástica/genética , Medula Óssea/patologia , Criança , Pré-Escolar , Biologia Computacional , Índices de Eritrócitos , Feminino , Predisposição Genética para Doença , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hidropisia Fetal/diagnóstico , Hidropisia Fetal/genética , Masculino , Mutação , Piruvato Quinase/deficiência , Piruvato Quinase/genética , Erros Inatos do Metabolismo dos Piruvatos/diagnóstico , Erros Inatos do Metabolismo dos Piruvatos/genética , Doenças Raras , Adulto Jovem
20.
Blood Cancer J ; 8(3): 25, 2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29535299

RESUMO

We analyzed 597 patients with myeloproliferative neoplasms (MPN) who presented transient ischemic attacks (TIA, n = 270) or ischemic stroke (IS, n = 327). Treatment included aspirin, oral anticoagulants, and cytoreductive drugs. The composite incidence of recurrent TIA and IS, acute myocardial infarction (AMI), and cardiovascular (CV) death was 4.21 and 19.2%, respectively at one and five years after the index event, an estimate unexpectedly lower than reported in the general population. Patients tended to replicate the first clinical manifestation (hazard ratio, HR: 2.41 and 4.41 for recurrent TIA and IS, respectively); additional factors for recurrent TIA were previous TIA (HR: 3.40) and microvascular disturbances (HR: 2.30); for recurrent IS arterial hypertension (HR: 4.24) and IS occurrence after MPN diagnosis (HR: 4.47). CV mortality was predicted by age over 60 years (HR: 3.98), an index IS (HR: 3.61), and the occurrence of index events after MPN diagnosis (HR: 2.62). Cytoreductive therapy was a strong protective factor (HR: 0.24). The rate of major bleeding was similar to the general population (0.90 per 100 patient-years). In conclusion, the long-term clinical outcome after TIA and IS in MPN appears even more favorable than in the general population, suggesting an advantageous benefit-risk profile of antithrombotic and cytoreductive treatment.


Assuntos
Antineoplásicos/administração & dosagem , Isquemia Encefálica , Fibrinolíticos/administração & dosagem , Neoplasias Hematológicas , Transtornos Mieloproliferativos , Inibidores da Agregação de Plaquetas/administração & dosagem , Acidente Vascular Cerebral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/mortalidade , Intervalo Livre de Doença , Feminino , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/mortalidade , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Taxa de Sobrevida
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