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BACKGROUND: Sodium glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and the nonsteroidal mineralocorticoid receptor antagonist (ns-MRA) finerenone all individually reduce cardiovascular, kidney, and mortality outcomes in patients with type 2 diabetes and albuminuria. However, the lifetime benefits of combination therapy with these medicines are not known. METHODS: We used data from 2 SGLT2i trials (CANVAS [Canagliflozin Cardiovascular Assessment] and CREDENCE [Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation]), 2 ns-MRA trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Diabetic Kidney Disease]), and 8 GLP-1 RA trials to estimate the relative effects of combination therapy versus conventional care (renin-angiotensin system blockade and traditional risk factor control) on cardiovascular, kidney, and mortality outcomes. Using actuarial methods, we then estimated absolute risk reductions with combination SGLT2i, GLP-1 RA, and ns-MRA in patients with type 2 diabetes and at least moderately increased albuminuria (urinary albumin:creatinine ratio ≥30 mg/g) by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE. RESULTS: Compared with conventional care, the combination of SGLT2i, GLP-1 RA, and ns-MRA was associated with a hazard ratio of 0.65 (95% CI, 0.55-0.76) for major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death). The corresponding estimated absolute risk reduction over 3 years was 4.4% (95% CI, 3.0-5.7), with a number needed to treat of 23 (95% CI, 18-33). For a 50-year-old patient commencing combination therapy, estimated major adverse cardiovascular event-free survival was 21.1 years compared with 17.9 years for conventional care (3.2 years gained [95% CI, 2.1-4.3]). There were also projected gains in survival free from hospitalized heart failure (3.2 years [95% CI, 2.4-4.0]), chronic kidney disease progression (5.5 years [95% CI, 4.0-6.7]), cardiovascular death (2.2 years [95% CI, 1.2-3.0]), and all-cause death (2.4 years [95% CI, 1.4-3.4]). Attenuated but clinically relevant gains in event-free survival were observed in analyses assuming 50% additive effects of combination therapy, including for major adverse cardiovascular events (2.4 years [95% CI, 1.1-3.5]), chronic kidney disease progression (4.5 years [95% CI, 2.8-5.9]), and all-cause death (1.8 years [95% CI, 0.7-2.8]). CONCLUSIONS: In patients with type 2 diabetes and at least moderately increased albuminuria, combination treatment of SGLT2i, GLP-1 RA, and ns-MRA has the potential to afford relevant gains in cardiovascular and kidney event-free and overall survival.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Canagliflozina/uso terapêutico , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon , Albuminúria/tratamento farmacológico , Rim , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Peptídeo 1 Semelhante ao Glucagon/uso terapêuticoRESUMO
The population of adult survivors of childhood cancer continues to grow as survival rates improve. Although it is well established that these survivors experience various complications and comorbidities related to their malignancy and treatment, this risk is modified by many factors that are not directly linked to their cancer history. Research evaluating the influence of patient-specific demographic and genetic factors, premorbid and comorbid conditions, health behaviors, and aging has identified additional risk factors that influence cancer treatment-related toxicity and possible targets for intervention in this population. Furthermore, although current long-term follow-up guidelines comprehensively address specific therapy-related risks and provide screening recommendations, the risk profile of the population continues to evolve with ongoing modification of treatment strategies and the emergence of novel therapeutics. To address the multifactorial modifiers of cancer treatment-related health risk and evolving treatment approaches, a patient-centered and risk-adapted approach to care that often requires a multidisciplinary team approach, including medical and behavioral providers, is necessary for this population. CA Cancer J Clin 2018;68:133-152. © 2018 American Cancer Society.
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Sobreviventes de Câncer , Neoplasias/complicações , Neoplasias/psicologia , Assistência Centrada no Paciente , Adulto , Fatores Etários , Criança , Comportamentos Relacionados com a Saúde , Acessibilidade aos Serviços de Saúde , Humanos , Neoplasias/terapia , Qualidade de Vida , Fatores de RiscoRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: We investigated the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase 1 open-label trial followed by a phase 2 randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase 1, intravenous administration of hcMSCs at 2 doses (1 × 106 and 5 × 105 cells/kg) was safe and well tolerated in 20 subjects. Because there was no difference between the 2 dosage groups (P = .9), it was decided to administer low-dose hcMSCs only for phase 2. In phase 2, subjects receiving 3 weekly intravenous infusions of hcMSCs at 5 × 105 cells/kg showed a higher proportion of an Eczema Area and Severity Index (EASI)-50 response at week 12 compared to the placebo group (P = .038). The differences between groups in the Dermatology Life Quality Index and pruritus numeric rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: The hcMSC treatment resulted in a significantly higher rate of EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSC treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.
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BACKGROUND: The association between low-frequency human immunodeficiency virus type 1 (HIV-1) drug resistance mutations (DRMs) and treatment failure (TF) is controversial. We explore this association using next-generation sequencing (NGS) methods that accurately sample low-frequency DRMs. METHODS: We enrolled women with HIV-1 in Malawi who were either antiretroviral therapy (ART) naive (cohort A), had ART failure (cohort B), or had discontinued ART (cohort C). At entry, cohorts A and C began a nonnucleoside reverse transcriptase inhibitor-based regimen and cohort B started a protease inhibitor-based regimen. We used Primer ID MiSeq to identify regimen-relevant DRMs in entry and TF plasma samples, and a Cox proportional hazards model to calculate hazard ratios (HRs) for entry DRMs. Low-frequency DRMs were defined as ≤20%. RESULTS: We sequenced 360 participants. Cohort B and C participants were more likely to have TF than cohort A participants. The presence of K103N at entry significantly increased TF risk among A and C participants at both high and low frequency, with HRs of 3.12 (95% confidence interval [CI], 1.58-6.18) and 2.38 (95% CI, 1.00-5.67), respectively. At TF, 45% of participants showed selection of DRMs while in the remaining participants there was an apparent lack of selective pressure from ART. CONCLUSIONS: Using accurate NGS for DRM detection may benefit an additional 10% of patients by identifying low-frequency K103N mutations.
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Farmacorresistência Viral , Infecções por HIV , HIV-1 , Mutação , Falha de Tratamento , Humanos , HIV-1/genética , HIV-1/efeitos dos fármacos , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Farmacorresistência Viral/genética , Adulto , Malaui , Fármacos Anti-HIV/uso terapêutico , Sequenciamento de Nucleotídeos em Larga Escala , Estudos de Coortes , Adulto Jovem , Resultado do TratamentoRESUMO
BACKGROUND: Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care. METHODS: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events. RESULTS: At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA2DS2-VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289-421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%-80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P=0.001). Acute major adverse events occurred in 1.9% of patients. CONCLUSIONS: In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.
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Fibrilação Atrial , Flutter Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/tratamento farmacológico , Estudos Retrospectivos , Volume Sistólico , Função Ventricular Esquerda , Resultado do Tratamento , Flutter Atrial/etiologia , Sistema de Registros , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , RecidivaRESUMO
BACKGROUND: Long-term outcomes of antiplatelet monotherapy in patients who receive percutaneous coronary intervention are unknown. The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) Extended study reports the posttrial follow-up results of the original HOST-EXAM trial. METHODS: From March 2014 through May 2018, 5438 patients who maintained dual antiplatelet therapy without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents were randomly assigned in a 1:1 ratio to receive clopidogrel (75 mg once daily) or aspirin (100 mg once daily). The primary end point (a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission attributable to acute coronary syndrome, and Bleeding Academic Research Consortium type 3 or greater bleeding), secondary thrombotic end point (cardiac death, nonfatal myocardial infarction, ischemic stroke, readmission attributable to acute coronary syndrome, and definite or probable stent thrombosis), and bleeding end point (Bleeding Academic Research Consortium type 2 or greater bleeding) were analyzed during the extended follow-up period. Analysis was performed on the per-protocol population (2431 patients in the clopidogrel group and 2286 patients in the aspirin group). RESULTS: During a median follow-up of 5.8 years (interquartile range, 4.8-6.2 years), the primary end point occurred in 12.8% and 16.9% in the clopidogrel and aspirin groups, respectively (hazard ratio, 0.74 [95% CI, 0.63-0.86]; P<0.001). The clopidogrel group had a lower risk for the secondary thrombotic end point (7.9% versus 11.9%; hazard ratio, 0.66 [95% CI, 0.55-0.79]; P<0.001) and secondary bleeding end point (4.5% versus 6.1%; hazard ratio, 0.74 [95% CI, 0.57-0.94]; P=0.016). There was no significant difference in the incidence of all-cause death between the 2 groups (6.2% versus 6.0%; hazard ratio, 1.04 [95% CI, 0.82-1.31]; P=0.742). Landmark analysis at 2 years showed that the beneficial effect of clopidogrel was consistent throughout the follow-up period. CONCLUSIONS: During an extended follow-up of >5 years after randomization, clopidogrel monotherapy compared with aspirin monotherapy was associated with lower rates of the composite net clinical outcome in patients without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02044250.
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Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Trombose , Humanos , Clopidogrel/uso terapêutico , Aspirina/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/cirurgia , Quimioterapia Combinada , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/tratamento farmacológico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Intervenção Coronária Percutânea/efeitos adversos , Trombose/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Concerns have been raised about the long-term performance of aortic stent grafts for the treatment of abdominal aortic aneurysms, in particular, unibody stent grafts (eg, Endologix AFX AAA stent grafts). Only limited data sets are available to evaluate the long-term risks related to these devices. The SAFE-AAA Study (Comparison of Unibody and Non-Unibody Endografts for Abdominal Aortic Aneurysm Repair in Medicare Beneficiaries Study) was designed with the Food and Drug Administration to provide a longitudinal assessment of the safety of unibody aortic stent grafts among Medicare beneficiaries. METHODS: The SAFE-AAA Study was a prespecified, retrospective cohort study evaluating whether unibody aortic stent grafts are noninferior to non-unibody aortic stent grafts with respect to the composite primary outcome of aortic reintervention, rupture, and mortality. Procedures were evaluated from August 1, 2011, through December 31, 2017. The primary end point was evaluated through December 31, 2019. Inverse probability weighting was used to account for imbalances in observed characteristics. Sensitivity analyses were used to evaluate the effect of unmeasured confounding, including assessment of the falsification end points heart failure, stroke, and pneumonia. A prespecified subgroup included patients treated from February 22, 2016, through December 31, 2017, corresponding to the market release of the most contemporary unibody aortic stent grafts (Endologix AFX2 AAA stent graft). RESULTS: Of 87 163 patients who underwent aortic stent grafting at 2146 US hospitals, 11 903 (13.7%) received a unibody device. The average age of the total cohort was 77.0±6.7 years, 21.1% were female, 93.5% were White, 90.8% had hypertension, and 35.8% used tobacco. The primary end point occurred in 73.4% of unibody device-treated patients versus 65.0% of non-unibody device-treated patients (hazard ratio, 1.19 [95% CI, 1.15-1.22]; noninferior P value of 1.00; median follow-up, 3.4 years). Falsification end points were negligibly different between groups. In the subgroup treated with contemporary unibody aortic stent grafts, the cumulative incidence of the primary end point occurred in 37.5% of unibody device-treated patients and 32.7% of non-unibody device-treated patients (hazard ratio, 1.06 [95% CI, 0.98-1.14]). CONCLUSIONS: In the SAFE-AAA Study, unibody aortic stent grafts failed to meet noninferiority compared with non-unibody aortic stent grafts with respect to aortic reintervention, rupture, and mortality. These data support the urgency of instituting a prospective longitudinal surveillance program for monitoring safety events related to aortic stent grafts.
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Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Feminino , Idoso , Estados Unidos , Idoso de 80 Anos ou mais , Masculino , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Estudos Retrospectivos , Estudos Prospectivos , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Medicare , Stents , Desenho de PróteseRESUMO
BACKGROUND: The contemporary measures of hospital performance for heart failure hospitalization and 30-day risk-standardized readmission rate (RSRR) and risk-standardized mortality rate (RSMR) are estimated using the same risk adjustment model and overall event rate for all patients. Thus, these measures are mainly driven by the care quality and outcomes for the majority racial and ethnic group, and may not adequately represent the hospital performance for patients of Black and other races. METHODS: Fee-for-service Medicare beneficiaries from January 2014 to December 2019 hospitalized with heart failure were identified. Hospital-level 30-day RSRR and RSMR were estimated using the traditional race-agnostic models and the race-specific approach. The composite race-specific performance metric was calculated as the average of the RSRR/RMSR measures derived separately for each race and ethnicity group. Correlation and concordance in hospital performance for all patients and patients of Black and other races were assessed using the composite race-specific and race-agnostic metrics. RESULTS: The study included 1 903 232 patients (75.7% White [n=1 439 958]; 14.5% Black [n=276 684]; and 9.8% other races [n=186 590]) with heart failure from 1860 hospitals. There was a modest correlation between hospital-level 30-day performance metrics for patients of White versus Black race (Pearson correlation coefficient: RSRR=0.42; RSMR=0.26). Compared with the race-agnostic RSRR and RSMR, composite race-specific metrics for all patients demonstrated stronger correlation with RSRR (correlation coefficient: 0.60 versus 0.74) and RSMR (correlation coefficient: 0.44 versus 0.51) for Black patients. Concordance in hospital performance for all patients and patients of Black race was also higher with race-specific (versus race-agnostic) metrics (RSRR=64% versus 53% concordantly high-performing; 61% versus 51% concordantly low-performing). Race-specific RSRR and RSMR metrics (versus race-agnostic) led to reclassification in performance ranking of 35.8% and 39.2% of hospitals, respectively, with better 30-day and 1-year outcomes for patients of all race groups at hospitals reclassified as high-performing. CONCLUSIONS: Among patients hospitalized with heart failure, race-specific 30-day RSMR and RSRR are more equitable in representing hospital performance for patients of Black and other races.
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Insuficiência Cardíaca , Readmissão do Paciente , Humanos , Idoso , Estados Unidos/epidemiologia , Medicare , Hospitalização , Hospitais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Mortalidade HospitalarRESUMO
In this prospective cohort of 2,006 individuals with non-MDR tuberculosis in India, 18% had unfavorable treatment outcomes (4.7% treatment failure, 2.5% recurrent infection, 4.1% death, 6.8% loss to follow-up) over a median 12-month follow-up period. Age, male sex, low education, nutritional status, and alcohol use were predictors of unfavorable outcomes.
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BACKGROUND: As stroke endovascular thrombectomy (EVT) treatment indications expand, understanding population-based EVT eligibility becomes critical for resource planning. We aimed to project current and future population-based EVT eligibility in the United States. METHODS: We conducted a post hoc analysis of the physician-adjudicated GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study; 2015 epoch), a population-based, cross sectional, observational study of stroke incidence, treatment, and outcomes across a 5-county region. All hospitalized patients ≥18 years of age with acute ischemic stroke were ascertained using the International Classification of Diseases, Ninth Revision codes 430-436 and Tenth Revision codes I60-I67 and G45-G46 and extrapolated to the US adult census 2020. We determined the rate of EVT eligibility within the GCNKSS population using time from last known well to presentation (0-5 versus 5-23 hours), presenting National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale. Both conservative and liberal estimates of prevalence of large vessel occlusion and large core were then applied based on literature review (unavailable within the 2015 GCNKSS). This eligibility was then extrapolated to the 2020 US population. RESULTS: Of the 1 057 183 adults within GCNKSS in 2015, 2741 had an ischemic stroke and 2176 had data available for analysis. We calculated that 8659 to 17 219 patients (conservative to liberal) meet the current guideline-recommended EVT criteria (nonlarge core, no prestroke disability, and National Institutes of Health Stroke Scale score ≥6) in the United States. Estimates (conservative to liberal) for expanded EVT eligibility subpopulations include (1) 5316 to 10 635 by large core; (2) 10 635 to 21 270 by mild presenting deficits with low National Institutes of Health Stroke Scale score; (3) 13 572 to 27 089 by higher prestroke disability; and (4) 7039 to 14 180 by >1 criteria. These expanded eligibility subpopulations amount to 36 562 to 73 174 patients. CONCLUSIONS: An estimated 8659 to 17 219 adult patients in the United States met strict EVT eligibility criteria in 2020. A 4-fold increase in population-based EVT eligibility can be anticipated with incremental adoption of recent or future positive trials. US stroke systems need to be rapidly optimized to handle all EVT-eligible patients with stroke.
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Procedimentos Endovasculares , Acidente Vascular Cerebral , Trombectomia , Humanos , Procedimentos Endovasculares/tendências , Feminino , Idoso , Masculino , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Estudos Transversais , Acidente Vascular Cerebral/cirurgia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Idoso de 80 Anos ou mais , AVC Isquêmico/cirurgia , AVC Isquêmico/epidemiologia , AVC Isquêmico/terapia , Adulto , Definição da ElegibilidadeRESUMO
Thrombolytic therapies for acute ischemic stroke are widely available but only result in recanalization early enough, to be therapeutically useful, in 10% to 30% of cases. This large gap in treatment effectiveness could be filled by novel therapies that can increase the effectiveness of thrombus clearance without significantly increasing the risk of harm. This focused update will describe the current state of emerging adjuvant treatments for acute ischemic stroke reperfusion. We focus on new treatments that are designed to (1) target different components that make up a stroke thrombus, (2) enhance endogenous fibrinolytic systems, (3) reduce stagnant blood flow, and (4) improve recanalization of distal thrombi and postendovascular thrombectomy.
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BACKGROUND: High-intensity therapy is recommended in current treatment guidelines for chronic poststroke aphasia. Yet, little is known about fatigue levels induced by treatment, which could interfere with rehabilitation outcomes. We analyzed fatigue experienced by people with chronic aphasia (>6 months) during high-dose interventions at 2 intensities. METHODS: A retrospective observational analysis was conducted on self-rated fatigue levels of people with chronic aphasia (N=173) collected during a previously published large randomized controlled trial of 2 treatments: constraint-induced aphasia therapy plus and multi-modality aphasia therapy. Interventions were administered at a higher intensity (30 hours over 2 weeks) or lower intensity (30 hours over 5 weeks). Participants rated their fatigue on an 11-point scale before and after each day of therapy. Data were analyzed using Bayesian ordinal multilevel models. Specifically, we considered changes in self-rated participant fatigue across a therapy day and over the intervention period. RESULTS: Data from 144 participants was analyzed. Participants were English speakers from Australia or New Zealand (mean age, 62 [range, 18-88] years) with 102 men and 42 women. Most had mild (n=115) or moderate (n=52) poststroke aphasia. Median ratings of the level of fatigue by people with aphasia were low (1 on a 0-10-point scale) at the beginning of the day. Ratings increased slightly (+1.0) each day after intervention, with marginally lower increases in the lower intensity schedule. There was no evidence of accumulating fatigue over the 2- or 5-week interventions. CONCLUSIONS: Findings suggest that intensive intervention was not associated with large increases in fatigue for people with chronic aphasia enrolled in the COMPARE trial (Constraint-Induced or Multimodality Personalised Aphasia Rehabilitation). Fatigue did not change across the course of the intervention. This study provides evidence that intensive treatment was minimally fatiguing for stroke survivors with chronic aphasia, suggesting that fatigue is not a barrier to high-intensity treatment.
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Afasia , Fadiga , Humanos , Afasia/etiologia , Afasia/reabilitação , Afasia/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Fadiga/etiologia , Fadiga/terapia , Adulto , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Doença Crônica , Acidente Vascular Cerebral/complicações , Adolescente , Adulto Jovem , Reabilitação do Acidente Vascular Cerebral/métodos , AutorrelatoRESUMO
The Get With The Guidelines-Stroke program which, began 20 years ago, is one of the largest and most important nationally representative disease registries in the United States. Its importance to the stroke community can be gauged by its sustained growth and widespread dissemination of findings that demonstrate sustained increases in both the quality of care and patient outcomes over time. The objectives of this narrative review are to provide a brief history of Get With The Guidelines-Stroke, summarize its major successes and impact, and highlight lessons learned. Looking to the next 20 years, we discuss potential challenges and opportunities for the program.
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Acidente Vascular Cerebral , Humanos , História do Século XXI , Guias de Prática Clínica como Assunto/normas , Sistema de Registros , Acidente Vascular Cerebral/terapia , Estados UnidosRESUMO
BACKGROUND: Fluoroquinolones lack approval for treatment of tularemia but have been used extensively for milder illness. Here, we evaluated fluoroquinolones for severe illness. METHODS: In an observational study, we identified case-patients with respiratory tularemia from July to November 2010 in Jämtland County, Sweden. We defined severe tularemia by hospitalization for >24 hours and severe bacteremic tularemia by Francisella tularensis subsp. holarctica growth in blood or pleural fluid. Clinical data and drug dosing were retrieved from electronic medical records. Chest images were reexamined. We used Kaplan-Meier curves to evaluate time to defervescence and hospital discharge. RESULTS: Among 67 case-patients (median age, 66 years; 81% males) 30-day mortality was 1.5% (1 of 67). Among 33 hospitalized persons (median age, 71 years; 82% males), 23 had nonbacteremic and 10 had bacteremic severe tularemia. Subpleural round consolidations, mediastinal lymphadenopathy, and unilateral pleural fluid were common on chest computed tomography. Among 29 hospitalized persons with complete outcome data, ciprofloxacin/levofloxacin (n = 12), ciprofloxacin/levofloxacin combinations with doxycycline and/or gentamicin (n = 11), or doxycycline as the single drug (n = 6) was used for treatment. One disease relapse occurred with doxycycline treatment. Treatment responses were rapid, with median fever duration 41.0 hours in nonbacteremic and 115.0 hours in bacteremic tularemia. Increased age-adjusted Charlson comorbidity index predicted severe bacteremic tularemia (odds ratio, 2.7 per score-point; 95% confidence interval, 1.35-5.41). A 78-year-old male with comorbidities and delayed ciprofloxacin/gentamicin treatment died. CONCLUSIONS: Fluoroquinolone treatment is effective for severe tularemia. Subpleural round consolidations and mediastinal lymphadenopathy were typical findings on computed tomography among case-patients in this study.
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Bacteriemia , Francisella tularensis , Francisella , Linfadenopatia , Tularemia , Masculino , Humanos , Idoso , Feminino , Tularemia/tratamento farmacológico , Doxiciclina/uso terapêutico , Fluoroquinolonas/uso terapêutico , Fluoroquinolonas/farmacologia , Levofloxacino/uso terapêutico , Ciprofloxacina/uso terapêutico , Resultado do Tratamento , Bacteriemia/tratamento farmacológico , Gentamicinas/uso terapêuticoRESUMO
In 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).
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Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Ucrânia/epidemiologia , Moldávia/epidemiologia , Cazaquistão/epidemiologia , Quirguistão/epidemiologia , República da Geórgia/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologiaRESUMO
BACKGROUND: Lenvatinib is approved as a first-line treatment for patients with unresectable and/or recurrent hepatocellular carcinoma (HCC). Lenvatinib achieved promising clinical benefits in REFLECT but was associated with clinically significant treatment-emergent hypertension (CSTE-HTN, a grouped term), a common class effect of tyrosine kinase inhibitors. This post hoc analysis assessed the impact of CSTE-HTN on the efficacy and safety of lenvatinib in HCC. METHODS: Patients from REFLECT who received lenvatinib (n = 476) were stratified according to CSTE-HTN. Tumors were assessed by mRECIST. Overall survival (OS) and progression-free survival (PFS) were evaluated using landmark analyses at 4 and 8 weeks. RESULTS: A total of 212 patients in the lenvatinib arm developed CSTE-HTN, and 264 did not. CSTE-HTN first occurred at 3.7 weeks (median); the worst grade CSTE-HTN occurred at 4.1 weeks (median). No patients had life-threatening CSTE-HTN and/or died due to CSTE-HTN. Median OS was numerically longer in patients with versus without CSTE-HTN (at 4 weeks: 16.3 vs. 11.6 months; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.621-1.004; at 8 weeks: 13.5 vs. 11.6 months; HR, 0.87; 95% CI, 0.696-1.089). Median PFS was similar between patients with and without CSTE-HTN (at 4 weeks: 6.6 vs. 6.4 months; HR, 0.887; 95% CI, 0.680-1.157; at 8 weeks: 5.7 vs. 6.4 months; HR, 1.09; 95% CI, 0.84-1.41). Objective response rate was numerically higher in patients with (48.6%) versus without CSTE-HTN (34.5%). CONCLUSIONS: In this retrospective analysis, CSTE-HTN was associated with improved OS but not PFS. CSTE-HTN did not impair the outcomes of patients with HCC treated with lenvatinib when detected early and managed appropriately.
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Carcinoma Hepatocelular , Hipertensão , Neoplasias Hepáticas , Compostos de Fenilureia , Quinolinas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Estudos Retrospectivos , Neoplasias Hepáticas/tratamento farmacológico , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/tratamento farmacológicoRESUMO
INTRODUCTION: Older adults with cancer facing competing treatments must prioritize between various outcomes. This study assessed health outcome prioritization among older adults with cancer starting chemotherapy. METHODS: Secondary analysis of a randomized trial addressing vulnerabilities in older adults with cancer. Patients completed three validated outcome prioritization tools: 1) Health Outcomes Tool: prioritizes outcomes (survival, independence, symptoms) using a visual analog scale; 2) Now vs. Later Tool: rates the importance of quality of life at three times-today versus 1 or 5 years in the future; and 3) Attitude Scale: rates agreement with outcome-related statements. The authors measured the proportion of patients prioritizing various outcomes and evaluated their characteristics. RESULTS: A total of 219 patients (median [range] age 71 [65-88], 68% with metastatic disease) were included. On the Health Outcomes Tool, 60.7% prioritized survival over other outcomes. Having localized disease was associated with choosing survival as top priority. On the Now vs. Later Tool, 50% gave equal importance to current versus future quality of life. On the Attitude Scale, 53.4% disagreed with the statement "the most important thing to me is living as long as I can, no matter what my quality of life is"; and 82.2% agreed with the statement "it is more important to me to maintain my thinking ability than to live as long as possible". CONCLUSION: Although survival was the top priority for most participants, some older individuals with cancer prioritize other outcomes, such as cognition and function. Clinicians should elicit patient-defined priorities and include them in decision-making.
Assuntos
Neoplasias , Preferência do Paciente , Qualidade de Vida , Humanos , Idoso , Feminino , Neoplasias/tratamento farmacológico , Neoplasias/psicologia , Masculino , Idoso de 80 Anos ou mais , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to describe treatment patterns and overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) in three countries between 2011 and 2020. METHODS: Three databases (US, Canada, Germany) were used to identify incident aNSCLC patients. OS was assessed from the date of incident aNSCLC diagnosis and, for patients who received at least a first line of therapy (1LOT), from the date of 1LOT initiation. In multivariable analyses, we analyzed the influence of index year and type of prescribed treatment on OS. FINDINGS: We included 51,318 patients with an incident aNSCLC diagnosis. The percentage of patients treated with a 1LOT differed substantially between countries, whereas the number of patients receiving immunotherapies/targeted treatments increased over time in all three countries. Median OS from the date of incident diagnosis was 9.9 months in the United States vs. 4.1 months in Canada. When measured from the start of 1LOT, patients had a median OS of 10.7 months in the United States, 10.9 months in Canada, and 10.9 months in Germany. OS from the start of 1LOT improved in all three countries from 2011 to 2020 by approximately 3 to 4 months. CONCLUSIONS: Observed continuous improvement in OS among patients receiving at least a 1LOT from 2011 to 2020 was likely driven by improved care and changes in the treatment landscape. The difference in the proportion of patients receiving a 1LOT in the observed countries requires further investigation.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Estados Unidos/epidemiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Alemanha/epidemiologia , Canadá/epidemiologiaRESUMO
BACKGROUND: Hot flashes are a common side effect of endocrine therapy (ET) that contribute to poor quality of life and decreased treatment adherence. METHODS: Patients with breast cancer wo were receiving ET and experiencing hot flashes were enrolled through three parallel, randomized trials conducted in the United States, China, and South Korea. Participants were randomized to either immediate acupuncture (IA) or delayed acupuncture control (DAC). IA participants received 20 acupuncture sessions over 10 weeks, whereas DAC participants received usual care, then crossed over to acupuncture with a reduced intensity. The primary end point was a change in score on the endocrine symptom subscale of the Functional Assessment of Cancer Therapy (FACT)-Endocrine Symptoms between baseline and week 10. Secondary end points included the hot flash score and the FACT-Breast score. A planned pooled analysis of individual patient data was performed using longitudinal mixed models. RESULTS: In total, 158 women with stage 0-III breast cancer were randomized (United States, n = 78; China, n = 40; South Korea, n = 40). At week 10, IA participants reported statistically significant improvements in the endocrine symptom subscale score (mean change ± standard error: 5.1 ± 0.9 vs. 0.2 ± 1.0; p = .0003), the hot flash score (-5.3 ± 0.9 vs. -1.4 ± 0.9; p < .003), and the FACT-Breast total score (8.0 ± 1.6 vs. -0.01 ± 1.6; p = .0005) compared with DAC participants. The effect of the acupuncture intervention differed by site (p = .005). CONCLUSIONS: Acupuncture led to statistically and clinically meaningful improvements in hot flashes, endocrine symptoms, and breast cancer-specific quality of life in women undergoing ET for breast cancer in the United States, China, and South Korea.
Assuntos
Terapia por Acupuntura , Neoplasias da Mama , Fogachos , Qualidade de Vida , Humanos , Feminino , Fogachos/terapia , Fogachos/induzido quimicamente , Neoplasias da Mama/terapia , Neoplasias da Mama/complicações , Pessoa de Meia-Idade , Terapia por Acupuntura/métodos , Adulto , Idoso , República da Coreia , Receptores de Estrogênio/metabolismo , Resultado do Tratamento , China , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Estados UnidosRESUMO
BACKGROUND: Recent studies suggest that early tumor shrinkage (ETS) and depth of response (DpR) reflect outcomes of chemotherapy in various cancers. This study evaluated the association of ETS and DpR with clinical outcomes using data from JCOG1113, which demonstrated the non-inferiority of gemcitabine plus S-1 (GS) to gemcitabine plus cisplatin (GC) for chemotherapy-naïve advanced biliary tract cancer. MATERIAL AND METHODS: In total, 354 (289 with measurable target lesions) patients enrolled in JCOG1113 were divided into ETS-unachieved and ETS-achieved groups (≥20% tumor reduction at week 6) and DpR-low and DpR-high groups (≥40% maximum shrinkage) until 12 weeks after enrollment. The impact of ETS and DpR on survival outcome was evaluated using the multivariable Cox proportional hazard model. RESULTS: The proportions of patients in the ETS-achieved and DpR-high groups were similar between the 2 treatment arms. The hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) for the ETS-achieved group were 0.70 (95% confidence interval (CI), 0.52-0.93) and 0.60 (95%CI, 0.44-0.81), respectively. The HRs of PFS and OS for the DpR-high group were 0.67 (95%CI, 0.48-0.94) and 0.64 (95%CI, 0.46-0.90), respectively. In the subpopulation treatment effect pattern plot analysis, most patients in the ETS-achieved group in the GC arm did not experience disease progression after 12 weeks from the landmark. CONCLUSION: As on-treatment markers, ETS and DpR were effective tools. ETS was clinically useful, because it can be used to evaluate the outcomes of treatment early at a specific time.