Citations

Abstract Choosing Wisely® is a medical stewardship and quality improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The ASH is an active participant in the Choosing Wisely® project. Using an iterative process and an evidence-based method, ASH has identified 5 tests and treatments that in some circumstances are not well supported by evidence and which in certain cases involve a risk of adverse events and financial costs with low likelihood of benefit. The ASH Choosing Wisely® recommendations focus on avoiding liberal RBC transfusion, avoiding thrombophilia testing in adults in the setting of transient major thrombosis risk factors, avoiding inferior vena cava filter usage except in specified circumstances, avoiding the use of plasma or prothrombin complex concentrate in the nonemergent reversal of vitamin K antagonists, and limiting routine computed tomography surveillance after curative-intent treatment of non-Hodgkin lymphoma. We recommend that clinicians carefully consider anticipated benefits of the identified tests and treatments before performing them.

AbstractDespite the advanced age at onset, chronic lymphocytic leukemia (CLL) shortens the life expectancy of the majority of newly diagnosed patients. The management of elderly patients with CLL is more complex than that of younger patients due to the greater frequency of comorbidities and functional impairment as well as reduced organ function. Many of the recent advances in the care of CLL patients (prognostication, more intense combination therapy regimens) are of unclear relevance for elderly patients. This review addresses 5 key questions in the management of elderly patients with CLL: (1) why is classifying the “fitness” of CLL patients necessary; (2) what criteria should be used to classify patient fitness; (3) when should elderly patients be treated; (4) how should therapy be selected for elderly patients; and (5) which therapy is best (for this patient)?

Building on diamond characteristics such as hardness, chemical inertness and low electron emission threshold voltage, the current microscopic, spectroscopic and voltammetric investigations are directed towards improving the properties of electrode coating materials for their future use in clinical studies of deep brain stimulation via fast-scan cyclic voltammetry (FSCV). In this study we combine the capabilities of confocal Raman mapping in providing detailed and accurate analysis of local distributions of material constituents in a series of boron-doped polycrystalline diamond films grown by chemical vapor deposition, with information from the more conventional techniques of scanning electron microscopy (SEM) and infrared absorption spectroscopy. Although SEM images show a uniform distribution of film crystallites, they have the limitation of being unable to differentiate the distribution of boron in the diamond. Values of 1018–1021 atoms/cm3 of boron content have been estimated from the absorption coefficient of the 1290 cm−1 infrared absorption band and from the 500 cm−1 Raman vibration. The observed accumulation of boron atoms and carbon sp2 impurities at the grain boundaries suggests that very high doping levels do not necessarily contribute to improvement of the material’s conductivity, corroborating with voltammetric data. FSCV results also indicate an enhanced stability of analyte detection.

AbstractIntroductionSubmaximal exercise testing (SET) assesses functional exercise capacity in pulmonary arterial hypertension (PAH) patients and provides additional physiologic information compared with the 6‐min walk test (6MWT). The relative correlations of the 6MWT and SET using SHAPE‐HF™ with other markers of PAH severity, particularly echocardiogram (ECHO)‐derived mean pulmonary artery pressure (MPAP), have not been investigated.Objectives(i) Examine the correlation between SHAPE measures with the 6‐min walk distance (6MWD), and (ii) Compare SHAPE parameters and the 6MWD to clinical measures of PAH severity.Methods Fifty‐five consecutive group 1 PAH outpatients were evaluated in a single pulmonary hypertension referral center from March 2011 to June 2012. Data collected: World Health Organization (WHO) functional class (FC), brain natriuretic peptide (BNP), ECHO, 6MWD and SHAPE results. Data are reported using mean ± standard deviation and Spearman correlation coefficients (r).ResultsNine patients were excluded. Of the 46 remaining patients, 78% were women and the average age was 61 ± 13 years. PAH characteristics: WHO FC III–IV 48%; idiopathic PAH 52%; BNP 198 ± 277 pg/mL; 6MWD 399 ± 97 m; ECHO right atrial pressure (RAP) 7 ± 4, pulmonary artery systolic pressure (PASP) 63 ± 29 and MPAP 45 ± 17 mmHg. SET with SHAPE results: mean partial pressure of end‐tidal (PET) CO2 31 ± 6 mmHg at end‐exercise; ventilatory efficiency (VE/VCO2) 43 ± 16. Significant correlations were found between the 6MWD and SHAPE variables: VE/VCO2 (r = –0.57, P < 0.0001) and end‐exercise PETCO2 (r = 0.42, P = 0.004). VE/VCO2 correlated with WHO FC, BNP, RAP, MPAP and PASP and 6MWD only with WHO FC, BNP and PASP.ConclusionSHAPE outperformed 6MWD in comparison with other measures of PAH disease severity.

Background and Purpose— Several accepted algorithms exist to characterize the risk of thromboembolism in atrial fibrillation. We performed a comparative analysis to assess the predictive value of 9 such schemes. Methods— In a longitudinal community-based cohort study from Olmsted County, Minnesota, 2720 residents with atrial fibrillation were followed up for 4.4±3.6 years±SD from 1990 to 2004. Risk factors were identified using a diagnostic index integrated with the electronic medical record. Thromboembolism and cardiovascular event data were collected and analyzed. Results— We identified 350 validated thromboembolic events in our cohort. Multivariable analysis identified age >75 years (odds ratio, 2.08; P <0.0001), female sex (odds ratio, 1.45; P =0.0015), history of hypertension (odds ratio, 3.07; P <0.0001), diabetes mellitus (odds ratio, 1.58; P =0.0003), and history of heart failure (odds ratio, 1.50; P =0.0102) as significant predictors of clinical thromboembolism. The Stroke Prevention in Atrial Fibrillation (SPAF; hazard ratio, 2.75; c =0.659), CHADS 2 -revised (hazard ratio, 3.48; c =0.654), and CHADS 2 -classical (hazard ratio, 2.90; c =0.653) risk schemes were most accurate in risk stratification. The low-risk cohort within the CHA 2 DS 2 -VASc scheme had the lowest event rate among all low-risk cohorts (0.11 per 100 person-years). Conclusions— A direct comparison of 9 risk schemes reveals no profound differences in risk stratification accuracy for high-risk patients. Accurate prediction of low-risk patients is perhaps more valuable in determining those unlikely to benefit from oral anticoagulation therapy. Among our cohort, CHA 2 DS 2 -VASc performed best in this purpose.

Background Contractile discordance exacerbates cardiac dysfunction, aggravating heart failure outcome. Dissecting the genesis of mechanical dyssynchrony would enable an early diagnosis before advanced disease. Methods and Results High‐resolution speckle‐tracking echocardiography was applied in a knockout murine surrogate of adult‐onset human cardiomyopathy caused by mutations in cardioprotective ATP‐sensitive K + (K ATP ) channels. Preceding the established criteria of cardiac dyssynchrony, multiparametric speckle‐based strain resolved nascent erosion of dysfunctional regions within cardiomyopathic ventricles of the K ATP channel–null mutant exposed to hemodynamic stress. Not observed in wild‐type counterparts, intraventricular disparity in wall motion, validated by the degree, direction, and delay of myocardial speckle patterns, unmasked the disease substrate from asymptomatic to overt heart failure. Mechanical dyssynchrony preceded widening of the QRS complex and exercise intolerance and progressed into global myocardial discoordination and decompensated cardiac pump function, precipitating a low output syndrome. Conclusions The present study, with the use of high‐resolution imaging, prospectively resolved the origin and extent of intraventricular motion disparity in a K ATP channel–knockout model of dilated cardiomyopathy. Mechanical dyssynchrony established as an early marker of cardiomyopathic disease offers novel insight into the pathodynamics of dyssynchronous heart failure.

SummaryBackgroundHighly selective 5‐HT4agonists have been suggested for the treatment of chronic constipation (CC).AimTo assess the effects of highly selective 5‐HT4agonists (prucalopride, velusetrag or naronapride) on patient‐important clinical efficacy outcomes and safety in adults withCC.MethodsWe searched the medical literature in January 2013 usingMEDLINE/Pubmed, Embase, Cochrane Library, and Web of Science/Scopus for randomised, controlled trials of highly selective 5‐HT4agonists in adults withCC, with no minimum duration of therapy (maximum 12 weeks) or date limitations. Data were extracted from intention‐to‐treat analyses, pooled using a random‐effects model, and reported as relative risk (RR), mean differences, or standardised mean differences with 95% confidence intervals (CI).ResultsMain outcomes included stool frequency, Patient‐Assessment of Constipation Quality of Life (PAC‐QOL),PACof symptoms (PAC‐SYM) and adverse events. Thirteen eligible trials were identified: 11 prucalopride, 1 velusetrag, 1 naronapride. Relative to control, treatment with highly selective 5‐HT4agonists was superior for all outcomes: mean ≥3 spontaneous complete bowel movements (SCBM)/week (RR = 1.85; 95%CI1.23–2.79); mean ≥1SCBMover baseline (RR = 1.57; 95%CI1.19, 2.06); ≥1 point improvement inPAC‐QOLandPAC‐SYMscores. The only active comparator trial of prucalopride andPEG3350 suggestedPEG3350 is more efficacious for some end points. Adverse events were more common with highly selective 5‐HT4agonists, but were generally minor; headache was the most frequent. Most trials studied prucalopride.ConclusionDemonstration of efficacy on patient‐important outcomes and a favourable safety profile support the continued use and development of highly selective 5–HT4agonists in the treatment of chronic constipation.

AbstractIn cancer clinical trials, patients often experience a recurrence of disease prior to the outcome of interest, overall survival. Additionally, for many cancers, there is a cured fraction of the population who will never experience a recurrence. There is often interest in how different covariates affect the probability of being cured of disease and the time to recurrence, time to death, and time to death after recurrence. We propose a multi‐state Markov model with an incorporated cured fraction to jointly model recurrence and death in colon cancer. A Bayesian estimation strategy is used to obtain parameter estimates. The model can be used to assess how individual covariates affect the probability of being cured and each of the transition rates. Checks for the adequacy of the model fit and for the functional forms of covariates are explored. The methods are applied to data from 12 randomized trials in colon cancer, where we show common effects of specific covariates across the trials. Copyright © 2013 John Wiley & Sons, Ltd.