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Molecular data and minimal residual disease (MRD) have been shown to influence outcomes in acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (AHCT). Here we developed and validated a novel AML-specific disease risk group (AML-DRG) and revised our previously developed hematopoietic cell transplant-composite risk (HCT-CR) model by incorporating molecular data and MRD status to predict outcomes of patients with AML. The study included 1414 consecutively treated adult AML patients who received a first AHCT. Patients were randomly assigned into training (nâ¯=â¯944) and validation (nâ¯=â¯470) sets. To develop the AML-DRG model, the coefficient of all significant AML-related variables in multivariable Cox regression analysis in a training dataset was converted into scores, whereas the AML-HCT-CR was the sum of disease-related factors assessed by the AML-DRG model with the addition of weighted scores from patient-related factors. The AML-DRG was developed by assigning the following scores: 1 point to secondary AML, 1 point to the European LeukaemiaNet adverse genetic risk, 2 points to complete remission with MRD positive/unknown, and 4 points to active disease. These scores were used to generate 3 risk groups of the AML-DRG with significantly different overall survivals. By adding the score for significant patient-related factors (HCT-specific comorbidity index/age), we created 4 risk groups of AML-HCT-CR with distinct survival outcomes. Both the AML-DRG and AML-HCT-CR provided significantly better discriminative capacity compared with the disease risk index, European LeukaemiaNet genetic risk model, and cytogenetic risk model. Prognostic models incorporating molecular data and MRD status allow better stratification and improved survival estimates of AML patients post-transplant.
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Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Modelos Biológicos , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Neoplasia Residual , Medição de Risco , Taxa de SobrevidaRESUMO
The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of the CDKN2C gene at chromosome region 1p32 (1p-), which is also associated with inferior outcomes. In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p- after high-dose therapy and autologous hematopoietic cell transplantation (auto-HCT). From January 2006 to December 2015, 1491 newly diagnosed patients with MM underwent upfront high-dose therapy and auto-HCT at our institution. Of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p- by FISH from the cohort of 899 patients. A control group (n = 287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above 2 cohorts, using a propensity score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p-. Patients were matched for age at auto-HCT, sex, International Staging System stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen, and maintenance therapy. Sixty-seven (79%), 4 (5%), and 14 (16%) patients had 1q+, 1p-, or both 1q+ and 1p-, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p- and the control group. The median follow-up time for all patients was 29.2 months (range, 0.29 to 84.96). The cumulative incidence of 100-day nonrelapse mortality was 1.2% and 0% for the 1q+/1p- and the control group, respectively. Forty-two patients (50%) in the 1q+/1p- group achieved complete response compared with 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 79% for the 1q+/1p- group and 56% and 86% for the control group. Patients in the 1q+/1p- group were at significantly increased risk of progression or death compared to the control group (hazard ratio [HR], 2.21; confidence interval [CI], 1.18 to 4.16; P = .014). No significant association between OS in the 2 groups was observed. The outcome of the 1q+/1p- alone (with no additional high-risk cytogenetics) and the propensity score matched control groups was also compared. Median PFS for the 1q+/1p- alone subgroup was 26.6 months, compared with 38.8 months for the control group (HR, 1.9; CI, 0.9 to 4.08; P = .09). The median OS had not been reached for the 1q+/1p- alone subgroup and was 81.1 months for the control group (HR, 1.25; CI, 0.3 to 4.6; P= .73). 1q+/1p- abnormalities with amplification of CKS1B and deletion ofCDKN2Cgenes were associated with shorter PFS compared with a propensity score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+/1p- patients with MM have improved with the use of more effective induction, conditioning, and maintenance therapy compared with historical controls, but we still need more effective therapeutic approaches to fully overcome the negative impact of 1q+/1p-.
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Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Cromossomos , Humanos , Hibridização in Situ Fluorescente , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Pontuação de Propensão , Estudos Retrospectivos , Transplante Autólogo , Resultado do TratamentoRESUMO
Hepatic arterial infusion pumps are increasingly utilized as an option for liver directed therapy in the treatment of metastatic colorectal carcinoma. After skeletonization of the hepatic artery through the ligation of extra-hepatic branches, these pumps are implanted surgically with their tip placed in the common hepatic artery. Subsequently, a nuclear medicine pump study is performed to ensure homogeneous perfusion of the liver and detect any extrahepatic perfusion. We report a peripheral arc between the superior mesenteric artery and celiac axis, which caused misperfusion on the SPECT nuclear medicine scan.
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Artéria Hepática/anormalidades , Artéria Hepática/cirurgia , Bombas de Infusão , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/administração & dosagem , Neoplasias Colorretais/patologia , Angiografia por Tomografia Computadorizada , Artéria Hepática/diagnóstico por imagem , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/secundário , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
BACKGROUND: Exposure to welding fume increases the risk of pneumococcal infection; whether such susceptibility extends to other respiratory infections is unclear. We report findings from a survey and from medical consultation data for workers in a large shipyard in the Middle East. METHODS: Between January 2013 and December 2013, we collected cross-sectional information from 529 male workers variously exposed to welding fume. Adjusted ORs for respiratory symptoms (cough, phlegm, wheezing, shortness of breath and 'chest illness') were estimated using multivariable logistic regression. Subsequently, we examined consultation records from 2000 to 2011 for 15â 954 workers who had 103â 840 consultations for respiratory infections; the associations between respiratory infections and levels of welding exposure were estimated using a count regression model with a negative binomial distribution. RESULTS: 13% of surveyed workers reported respiratory symptoms with a higher prevalence in winter, particularly among welders. The adjusted OR in welders versus other manual labourers was 1.72 (95% CI 1.02 to 3.01) overall and 2.31 (1.05 to 5.10) in winter months; no effect was observed in summer. The risk of consultation for respiratory infections was higher in welders than in manual labourers, with an adjusted incidence rate ratio of 1.45 (1.59 to 1.83) overall, 1.47 (1.42 to 1.52) in winter and 1.33 (1.23 to 1.44) in summer (interaction, p<0.001). CONCLUSIONS: The observation that respiratory symptoms and consultations for respiratory infection in welders are more common in winter may indicate an enhanced vulnerability to a broad range of infections. If confirmed, this would have important implications for the occupational healthcare of a very large, global workforce.
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Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Infecções Respiratórias/etiologia , Soldagem , Adulto , Idoso , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Testes de Função Respiratória , Infecções Respiratórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Estações do Ano , Navios , Emirados Árabes Unidos/epidemiologiaRESUMO
BACKGROUND: Health information technology (HIT) could improve care coordination by providing clinicians remote access to information, improving legibility, and allowing asynchronous communication, among other mechanisms. We sought to determine, from a clinician perspective, how care is coordinated and to what extent HIT is involved when transitioning patients between emergency departments, acute care hospitals, skilled nursing facilities, and home health agencies in settings across the United States. METHODS: We performed a qualitative study with clinicians and information technology professionals from six regions of the U.S. which were chosen as national leaders in HIT. We analyzed data through a two person consensus approach, assigning responses to each of nine care coordination activities. We also conducted a literature review of MEDLINE®, CINAHL®, and Embase, analyzing results of studies that examined interventions to improve information transfer during transitions of care. RESULTS: We enrolled 29 respondents from 17 organizations and conducted six focus groups. Respondents reported how HIT is currently used for care coordination activities. HIT is currently used to monitor patients and to align systems-level resources with population needs. However, we identified multiple areas where the lack of interoperability leads to inefficient processes and missing data. Additionally, the literature review identified ten intervention studies that address information transfer, seven of which employed HIT and three of which utilized other communication methods such as telephone calls, faxed records, and nurse case management. CONCLUSIONS: Significant care coordination gaps exist due to the lack of interoperability across the United States. We must design, evaluate, and incentivize the use of HIT for care coordination. We should focus on the domains where we found the largest gaps: information transfer, systems to monitor patients, tools to support patients' self-management goals, and tools to link patients and their caregivers with community resources.
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Continuidade da Assistência ao Paciente/normas , Informática Médica , Transferência de Pacientes/normas , Acesso à Informação , Adulto , Cuidadores , Comunicação , Feminino , Grupos Focais , Humanos , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Pesquisa Qualitativa , Autocuidado , Estados UnidosRESUMO
BACKGROUND: Physicians work considerably longer hours and are less satisfied with work-life balance than U.S. workers in other fields. There is, however, minimal data on physicians' parental satisfaction. METHODS: To evaluate differences in parental satisfaction among physicians and workers in other fields, we surveyed U.S. physicians as well as a probability-based sample of the general U.S. working population between August 2014-October 2014. Parental satisfaction and the perceived impact of career on relationships with children were evaluated. RESULTS: Among 6880 responding physicians (cooperation rate 19.2 %), 5582 (81.1 %) had children. Overall, physicians were satisfied in their relationships with their children, with 4782 (85.9 %) indicating that they were either very satisfied [n = 2738; (49.2 %)] or satisfied [n = 2044 (36.7 %)]. In contrast, less than half believed their career had made either a major [n = 1212; (21.8 %)] or minor positive [n = 1260; (22.7 %)] impact on their relationship with their children, with a slightly larger proportion indicating a major (n = 2071 [37.2 %]) or minor (n = 501 [9 %]) negative impact. Women physicians were less likely to believe their career had made a positive impact as were younger physicians. Hours worked/week inversely correlated with the belief that career had made a positive impact on relationships with children. Both men (OR: 2.75; p < 0.0001) and women (OR: 4.33; p < 0.0001) physicians were significantly more likely to report that their career had a negative impact on relationships with their children than the sex-matched U.S. working population. CONCLUSIONS: U.S. physicians report generally high satisfaction in their relationships with their children. Despite their high satisfaction, physicians have a more negative perception of the impact of their career on relationships with their children than U.S. workers in general.
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Relações Pais-Filho , Pais/psicologia , Satisfação Pessoal , Médicos/psicologia , Carga de Trabalho/psicologia , Adaptação Psicológica , Adulto , Escolha da Profissão , Criança , Feminino , Humanos , Satisfação no Emprego , Masculino , Médicos/estatística & dados numéricos , Apoio Social , Estados Unidos/epidemiologia , Carga de Trabalho/estatística & dados numéricosRESUMO
OBJECTIVE: The objective was to quantitatively and qualitatively examine the efficacy of DBT (e.g., decreasing life-threatening suicidal and parasuicidal acts, attrition, and depression) explicitly with borderline personality disorder (BPD) and using conservative assumptions and criteria, across treatment providers and settings. METHOD: Five randomized controlled trials (RCTs) were identified in a systematic search that examined the efficacy of DBT in reducing suicide attempts, parasuicidal behavior, attrition during treatment, or symptoms of depression, in adult patients with BPD. RESULTS: Combining effect measures for suicide and parasuicidal behavior (five studies total) revealed a net benefit in favor of DBT (pooled Hedges' g -0.622). DBT was only marginally better than treatment as usual (TAU) in reducing attrition during treatment in five RCTs (pooled risk difference -0.168). DBT was not significantly different from TAU in reducing depression symptoms in three RCTs (pooled Hedges' g -0.896). DISCUSSION: DBT demonstrates efficacy in stabilizing and controlling self-destructive behavior and improving patient compliance.
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BACKGROUND: Vascular access complications remain the leading cause of morbidity after cardiac catheterization procedures. Fluoroscopy-guided vascular access has been recommended to reduce these complications. However, the use of current recommendations still results in arterial access above the inferior epigastric artery (IEA) (high stick) or below the common femoral artery (CFA) bifurcation (low stick). OBJECTIVES: The goal of our study was to evaluate the influence of patient characteristics like age, body mass index, and pelvic anatomy on current recommendations. METHODS: We prospectively collected clinical, anatomic, and angiographic data on 631 consecutive patients who underwent coronary and noncoronary procedures via CFA access. Anatomic location of IEA loop, CFA bifurcation, public tubercle (PT), and anterior superior iliac spine were identified in relationship to the femoral head Location of IEA loop was used as a surrogate for inguinal ligament (IL). RESULTS: Approximately 12% of patients had a low-lying IEA loop (group B). These patients had a significantly higher BMI compared with patients with IEA loop above the centerline of femoral head (group A) (P = 0.018). The anatomic location of PT was below the lower border of femoral head significantly more frequently in group B compared to group A (P < 0.0001). Fifteen percent of patients had a high CFA bifurcation. On clinical follow-up during index hospitalization, there was no significant difference between the two groups, in terms of complications including retroperitoneal hemorrhage, access site hematoma >5 cm, bleeding requiring transfusion or pseudoaneurysm. CONCLUSIONS: Anatomic location of PT on fluoroscopy can be used as an additional surrogate to predict the location of IL. Patients with high BMI have a low lying IL, which may predispose them to "high sticks." The location of IEA cannot be used as a surrogate for IL in all patients.
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Cateterismo Periférico/normas , Artéria Femoral/diagnóstico por imagem , Fidelidade a Diretrizes/normas , Guias de Prática Clínica como Assunto/normas , Radiografia Intervencionista/normas , Idoso , Pontos de Referência Anatômicos , Falso Aneurisma/etiologia , Índice de Massa Corporal , Cateterismo Periférico/efeitos adversos , Distribuição de Qui-Quadrado , Artérias Epigástricas/diagnóstico por imagem , Feminino , Cabeça do Fêmur/diagnóstico por imagem , Fluoroscopia/normas , Hematoma/etiologia , Hemorragia/etiologia , Humanos , Ílio/diagnóstico por imagem , Ligamentos/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Osso Púbico/diagnóstico por imagem , Punções , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Accurately identifying cognitive changes in Mexican American (MA) adults using the Mini-Mental State Examination (MMSE) requires knowledge of population-based norms for the MMSE, a scale which has widespread use in research settings. OBJECTIVE: To describe the distribution of MMSE scores in a large cohort of MA adults, assess the impact of MMSE requirements on their clinical trial eligibility, and explore which factors are most strongly associated with their MMSE scores. METHODS: Visits between 2004-2021 in the Cameron County Hispanic Cohort were analyzed. Eligible participants were ≥18 years old and of Mexican descent. MMSE distributions before and after stratification by age and years of education (YOE) were assessed, as was the proportion of trial-aged (50-85- year-old) participants with MMSE <24, a minimum MMSE cutoff most frequently used in Alzheimer's disease (AD) clinical trials. As a secondary analysis, random forest models were constructed to estimate the relative association of the MMSE with potentially relevant variables. RESULTS: The mean age of the sample set (nâ=â3,404) was 44.4 (SD, 16.0) years old and 64.5% female. Median MMSE was 28 (IQR, 28-29). The percentage of trial-aged participants (nâ=â1,267) with MMSE <24 was 18.6% overall and 54.3% among the subset with 0-4 YOE (nâ=â230). The five variables most associated with the MMSE in the study sample were education, age, exercise, C-reactive protein, and anxiety. CONCLUSION: The minimum MMSE cutoffs in most phase III prodromal-to-mild AD trials would exclude a significant proportion of trial-aged participants in this MA cohort, including over half of those with 0-4 YOE.
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Doença de Alzheimer , Testes de Estado Mental e Demência , Americanos Mexicanos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Escolaridade , Americanos Mexicanos/psicologia , Texas , Valores de Referência , Adulto , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Several interventions promote axonal growth and functional recovery when initiated shortly after central nervous system injury, including blockade of myelin-derived inhibitors with soluble Nogo receptor (NgR1, RTN4R) decoy protein. We examined the efficacy of this intervention in the much more prevalent and refractory condition of chronic spinal cord injury. METHODS: We eliminated the NgR1 pathway genetically in mice by conditional gene targeting starting 8 weeks after spinal hemisection injury and monitored locomotion in the open field and by video kinematics over the ensuing 4 months. In a separate pharmacological experiment, intrathecal NgR1 decoy protein administration was initiated 3 months after spinal cord contusion injury. Locomotion and raphespinal axon growth were assessed during 3 months of treatment between 4 and 6 months after contusion injury. RESULTS: Conditional deletion of NgR1 in the chronic state results in gradual improvement of motor function accompanied by increased density of raphespinal axons in the caudal spinal cord. In chronic rat spinal contusion, NgR1 decoy treatment from 4 to 6 months after injury results in 29% (10 of 35) of rats recovering weight-bearing status compared to 0% (0 of 29) of control rats (p < 0.05). Open field Basso, Beattie, and Bresnahan locomotor scores showed a significant improvement in the NgR-treated group relative to the control group (p < 0.005, repeated measures analysis of variance). An increase in raphespinal axon density caudal to the injury is detected in NgR1 decoy-treated animals by immunohistology and by positron emission tomography using a serotonin reuptake ligand. INTERPRETATION: Antagonizing myelin-derived inhibitors signaling with NgR1 decoy augments recovery from chronic spinal cord injury.
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Axônios/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Proteínas Recombinantes de Fusão/farmacologia , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Modelos Animais de Doenças , Injeções Espinhais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas da Mielina/deficiência , Proteínas da Mielina/genética , Testes Neuropsicológicos , Proteínas Nogo , Proteínas Recombinantes de Fusão/administração & dosagem , Traumatismos da Medula Espinal/metabolismo , Fatores de Tempo , Resultado do TratamentoRESUMO
Collusion occurs when multiple malicious participants of a distributed protocol work together to sabotage or spy on honest participants. decentralized protocols often rely on a subset of participants called workers for critical operations. Collusion between workers can be particularly harmful to the security of the protocol. We propose two protocols that select a subset of workers from the set of participants such that the probability of the workers colluding together is minimized. Our first solution is a decentralized protocol that randomly selects workers in a verifiable manner without any trusted entities. The second solution is an algorithm that uses a social graph of participants and community detection to select workers that are socially distant in order to reduce the probability of collusion. We present our solutions in the context of a decentralized voting protocol proposed by Schiedermeier et al. (A transparent referendum protocol with immutable proceedings and verifiable outcome for trustless networks, Springer, Cham, 2019) that guarantees transparency and verifiability. Enabling collusion-resistance in order to ensure democratic voting is clearly of paramount importance thus the voting protocol provides a suitable use case for our solutions.
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Bangladesh is a maritime country with an area of 118000 km2 which supports a large number of commercially important species. Currently seaweeds are considered as important component of blue economy development in Bangladesh and farming is practiced at small scale level (Hypnea spp, Caulerpha reacemosa, Gelidium sp. are cultured). For the expansion of the seaweed farming in Bangladesh, a complete understanding of social and economic status of current farmers is important. However, information on socio-economic status of seaweed industry in Bangladesh is very limited. Therefore, this study aimed to understand existing culture methods and their cost, marketing channel and problems with seaweed farming in south east coast of Bangladesh. We used questionnaire survey and focus group discussions to collect data from seaweed farmers, researchers, local community and entrepreneurs. The study found that farmers are currently practicing long-line and horizontal net methods for the seaweed farming in the south east coastal region. The study also found that these culture methods are economically profitable. Seaweeds are currently sold locally and a proper value chain for seaweed marketing is still missing. Existing seaweed farmers are facing the problems related to insufficient credits for starting seaweed farming, lack of proper guidelines for farming and processing of harvested seaweed. This study suggests that for industrial level expansion of seaweed production in Bangladesh a proper value chain, development of seaweed derived products, farm monitoring systems, smooth seed supply and information hubs are required.
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INTRODUCTION: This study aimed to determine if thromboelastography (TEG) is associated with reduced blood product use and surgical reintervention following cardiopulmonary bypass (CPB) compared to traditional coagulation tests. METHODS: A retrospective review was conducted of 698 patients who underwent CPB at a tertiary-care, community-based, university-affiliated hospital from February 16, 2014 to February 16, 2015 (Period I) and from May 16, 2015 to May 16, 2016 (Period II). Traditional coagulation tests guided transfusion during Period I and TEG guided transfusion during Period II. Intraoperative and postoperative administration of blood products (red blood cells, fresh frozen plasma, platelets, and cryoprecipitate), reoperation for hemorrhage or graft occlusion, duration of mechanical ventilation, hospital length of stay, and mortality were recorded. RESULTS: Use of a TEG-directed algorithm was associated with a 13.5% absolute reduction in percentage of patients requiring blood products intraoperatively (48.2% vs. 34.7%, p < 0.001). TEG resulted in a 64.3% and 43.1% reduction in proportion of patients receiving fresh frozen plasma (FFP) and platelets, respectively, with a 50% reduction in volume of FFP administered (0.3 vs. 0.6 units, p < 0.001). Use of TEG was not observed to decrease postoperative blood product usage or mortality significantly. The median length of hospital stay was reduced by one day after TEG guided transfusion was implemented (nine days vs. eight days, p = 0.01). CONCLUSIONS: Use of TEG-directed transfusion of blood products following CPB appeared to decrease the need for intraoperative transfusions, but the effect on clinical outcomes has yet to be clearly determined.
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BACKGROUND: Prior studies have found a reduced risk of dementia of any etiology following influenza vaccination in selected populations, including veterans and patients with serious chronic health conditions. However, the effect of influenza vaccination on Alzheimer's disease (AD) risk in a general cohort of older US adults has not been characterized. OBJECTIVE: To compare the risk of incident AD between patients with and without prior influenza vaccination in a large US claims database. METHODS: Deidentified claims data spanning September 1, 2009 through August 31, 2019 were used. Eligible patients were free of dementia during the 6-year look-back period and≥65 years old by the start of follow-up. Propensity-score matching (PSM) was used to create flu-vaccinated and flu-unvaccinated cohorts with similar baseline demographics, medication usage, and comorbidities. Relative risk (RR) and absolute risk reduction (ARR) were estimated to assess the effect of influenza vaccination on AD risk during the 4-year follow-up. RESULTS: From the unmatched sample of eligible patients (nâ=â2,356,479), PSM produced a sample of 935,887 flu-vaccinated-unvaccinated matched pairs. The matched sample was 73.7 (SD, 8.7) years of age and 56.9% female, with median follow-up of 46 (IQR, 29-48) months; 5.1% (nâ=â47,889) of the flu-vaccinated patients and 8.5% (nâ=â79,630) of the flu-unvaccinated patients developed AD during follow-up. The RR was 0.60 (95% CI, 0.59-0.61) and ARR was 0.034 (95% CI, 0.033-0.035), corresponding to a number needed to treat of 29.4. CONCLUSION: This study demonstrates that influenza vaccination is associated with reduced AD risk in a nationwide sample of US adults aged 65 and older.
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Doença de Alzheimer , Influenza Humana , Adulto , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/epidemiologia , Doença Crônica , Estudos de Coortes , Feminino , Humanos , Influenza Humana/complicações , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Vacinação/efeitos adversosRESUMO
There is growing evidence for neuronal hyperexcitability in Alzheimer's disease. Hyperexcitability is associated with an increase in epileptiform activity and the disruption of inhibitory activity of interneurons. Interneurons fire at a high rate and are frequently associated with high-frequency oscillations in the gamma frequency band (30-150â Hz). It is unclear how hyperexcitability affects the organization of functional brain networks. A sample of 63 amnestic mild cognitive impairment patients underwent a magnetoencephalography resting-state recording with eyes closed. Twenty (31.75%) mild cognitive impairment patients had epileptiform activity. A cluster-based analysis of the magnetoencephalography functional connectivity revealed a region within the right temporal cortex whose global connectivity in the gamma frequency band was significantly reduced in patients with epileptiform activity relative to those without epileptiform activity. A subsequent seed-based analysis showed that this was largely due to weaker gamma band connectivity of this region with ipsilateral frontal and medial regions, and the upper precuneus area. In addition, this reduced functional connectivity was associated with higher grey matter atrophy across several cortical regions in the patients with epileptiform activity. These functional network disruptions and changes in brain physiology and morphology have important clinical implications as they may contribute to cognitive decline in mild cognitive impairment and Alzheimer's disease.
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Introduction: Cognitive impairment after concussion has been widely reported, but there is no reliable imaging biomarker that predicts the severity of cognitive decline post-concussion. This study tests the hypothesis that patients with a history of concussion and persistent cognitive impairment have fractional anisotropy (FA) and mean diffusivity (MD) values from diffusion tensor imaging (DTI) that are specifically associated with poor performance on the Montreal Cognitive Assessment (MoCA). Methods: Fifty-three subjects (19 females) with concussions and persistent cognitive symptoms had MR imaging and the MoCA. Imaging was analyzed by atlas-based, whole-brain DTI segmentation and FLAIR lesion segmentation. Then, we conducted a random forest-based recursive feature elimination (RFE) with 10-fold cross-validation on the entire dataset, and with partial correlation adjustment for age and lesion load. Results: RFE showed that 11 DTI variables were found to be important predictors of MoCA scores. Partial correlation analyses, corrected for age and lesion load, showed significant correlations between MoCA scores and right fronto-temporal regions: inferior temporal gyrus MD (r = -0.62, p = 0.00001), middle temporal gyrus MD (r = -0.54, p = 0.0001), angular gyrus MD (r = -0.48, p = 0.0008), and inferior frontal gyrus FA (r = 0.44, p = 0.002). Discussion: This is the first study to demonstrate a correlation between MoCA scores and DTI variables in patients with a history of concussion and persistent cognitive impairment. This kind of research will significantly increase our understanding of why certain persons have persistent cognitive changes after concussion which, in turn, may allow us to predict persistent impairment after concussion and suggest new interventions.
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Several common and debilitating neurodegenerative disorders are characterized by the intracellular accumulation of neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau protein. In Alzheimer's disease (AD), NFTs are accompanied by extracellular amyloid-beta (Aß), but primary tauopathy disorders are marked by the accumulation of tau protein alone, including forms of frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), among others. 18F-THK5351 has been reported to bind pathological tau as well as associated reactive astrogliosis. The goal of this study was to validate the ability of the PET tracer 18F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo 18F-THK5351 PET signaling over time in transgenic P301S tau mice from 8 months that had a positive correlation with histological and biochemical tau changes, as well as motor, memory, and learning impairment. This study indicates that 18F-THK5351 may help fill a critical need to develop PET imaging tracers that detect aberrant tau aggregation and related neuropathology in order to diagnose the onset of tauopathies, gain insights into their underlying pathophysiologies, and to have a reliable biomarker to follow during treatment trials.
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BACKGROUND: Previous studies of hospital readmission have focused on specific conditions or populations and generated complex prediction models. OBJECTIVE: To identify predictors of early hospital readmission in a diverse patient population and derive and validate a simple model for identifying patients at high readmission risk. DESIGN: Prospective observational cohort study. PATIENTS: Participants encompassed 10,946 patients discharged home from general medicine services at six academic medical centers and were randomly divided into derivation (n = 7,287) and validation (n = 3,659) cohorts. MEASUREMENTS: We identified readmissions from administrative data and 30-day post-discharge telephone follow-up. Patient-level factors were grouped into four categories: sociodemographic factors, social support, health condition, and healthcare utilization. We performed logistic regression analysis to identify significant predictors of unplanned readmission within 30 days of discharge and developed a scoring system for estimating readmission risk. RESULTS: Approximately 17.5% of patients were readmitted in each cohort. Among patients in the derivation cohort, seven factors emerged as significant predictors of early readmission: insurance status, marital status, having a regular physician, Charlson comorbidity index, SF12 physical component score, >or=1 admission(s) within the last year, and current length of stay >2 days. A cumulative risk score of >or=25 points identified 5% of patients with a readmission risk of approximately 30% in each cohort. Model discrimination was fair with a c-statistic of 0.65 and 0.61 for the derivation and validation cohorts, respectively. CONCLUSIONS: Select patient characteristics easily available shortly after admission can be used to identify a subset of patients at elevated risk of early readmission. This information may guide the efficient use of interventions to prevent readmission.
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Medicina de Família e Comunidade/tendências , Modelos Teóricos , Readmissão do Paciente/tendências , Adolescente , Adulto , Idoso , Estudos de Coortes , Medicina de Família e Comunidade/métodos , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
Theories of semantic memory based on neuropsychological findings have posited a distinction between stored semantic representations and the mechanisms used to access and manipulate them (e.g., Lambon Ralph, Jefferies, Patterson, & Rogers, 2017; Warrington & Cipolotti, 1996). The most recent instantiation of this view, the controlled semantic cognition theory (Lambon Ralph et al., 2017), is supported by findings suggesting that multimodal (i.e., both verbal and nonverbal) semantic deficits may result from qualitatively different impairments: on the one hand, damage to a semantic access mechanism related to executive control, which is observed in semantic aphasia (SA), and on the other, damage to semantic representations, which is observed in semantic dementia (SD) (Jefferies & Lambon Ralph, 2006). In this study we compared SA and SD patients on several phenomena previously used to support these distinctions. Contrary to the prior results, we found that (1) overall, cross-task consistency was equivalent for the two groups; (2) neither patient group showed consistency driven by item identity across different semantic tasks; (3) correlations among task performance were not obviously driven by the semantic control demands of different tasks; (4) both groups showed executive function deficits; and (5) both groups showed strong effects of distractor interference in a synonym judgment task. Furthermore, we investigated the components of executive ability that could underlie semantic control deficits by correlating performance on updating, shifting, and inhibition tasks with performance on tasks testing semantic abilities. We found that updating was related to semantic processing generally, whereas shifting and inhibition were not. These results also suggest that complex executive function tasks relate to semantic tasks through their shared relationship with language abilities. Overall, evidence from SA and SD patients does not differentiate representations and access mechanisms in the semantic system, as has previously been suggested. Implications for the storage-access distinction are discussed.
Assuntos
Afasia/psicologia , Demência Frontotemporal/psicologia , Memória , Semântica , Acidente Vascular Cerebral/psicologia , Afasia/fisiopatologia , Compreensão , Função Executiva/fisiologia , Demência Frontotemporal/fisiopatologia , Humanos , Julgamento , Memória/fisiologia , Testes Neuropsicológicos , Teoria Psicológica , Acidente Vascular Cerebral/fisiopatologiaRESUMO
PURPOSE: Allogeneic hematopoietic stem cell transplantation (AHCT) outcomes depend on disease and patient characteristics. We previously developed a novel prognostic model, hematopoietic cell transplant composite-risk (HCT-CR) by incorporating the refined disease risk index (DRI-R) and hematopoietic cell transplant-comorbidity/age index (HCT-CI/Age) to predict post-transplant survival in patients with acute myeloid leukemia and myelodysplastic syndrome. Here we aimed to validate and prove the generalizability of the HCT-CR model in an independent cohort of patients with hematologic malignancies receiving AHCT. EXPERIMENTAL DESIGN: Data of consecutive adult patients receiving AHCT for various hematologic malignancies were analyzed. Patients were stratified into four HCT-CR risk groups. The discrimination, calibration performance, and clinical net benefit of the HCT-CR model were tested. RESULTS: The HCT-CR model stratified patients into four risk groups with significantly different overall survival (OS). Three-year OS was 67.4%, 50%, 37.5%, and 29.9% for low, intermediate, high, and very high-risk group, respectively (P < 0.001). The HCT-CR model had better discrimination on OS prediction when compared with the DRI-R and HCT-CI/Age (C-index was 0.69 vs. 0.59 and 0.56, respectively, P < 0.001). The decision curve analysis showed that HCT-CR model provided better clinical utility for patient selection for post-transplant clinical trial than the "treat all" or "treat none" strategy and the use of the DRI-R and HCT-CI/Age model separately. CONCLUSIONS: The HCT-CR can be effectively used to predict post-transplant survival in patients with various hematologic malignancies. This composite model can identify patients who will benefit the most from transplantation and helps physicians in making decisions regarding post-transplant therapy to improve outcomes.