Citations

Background: Atrial fibrillation (AF) adversely impacts health-related quality of life (hrQoL). While some patients demonstrate improvements in hrQoL, the factors associated with large improvements in hrQoL are not well described. Methods: We assessed factors associated with a 1-year increase in the Atrial Fibrillation Effect on Quality-of-Life score of 1 SD (≥18 points; 3× clinically important difference), among outpatients in the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation I registry. Results: Overall, 28% (181/636) of patients had such a hrQoL improvement. Compared with patients not showing large hrQoL improvement, they were of similar age (median 73 versus 74, P =0.3), equally likely to be female (44% versus 48%, P =0.3), but more likely to have newly diagnosed AF at baseline (18% versus 8%; P =0.0004), prior antiarrhythmic drug use (52% versus 40%, P =0.005), baseline antiarrhythmic drug use (34.8% versus 26.8%, P =0.045), and more likely to undergo AF-related procedures during follow-up (AF ablation: 6.6% versus 2.0%, P =0.003; cardioversion: 12.2% versus 5.9%, P =0.008). In multivariable analysis, a history of alcohol abuse (adjusted OR, 2.41; P =0.01) and increased baseline diastolic blood pressure (adjusted OR, 1.23 per 10-point increase and >65 mm Hg; P =0.04) were associated with large improvements in hrQoL at 1 year, whereas patients with prior stroke/transient ischemic attack, chronic obstructive pulmonary disease, and peripheral arterial disease were less likely to improve ( P <0.05 for each). Conclusions: In this national registry of patients with AF, potentially treatable AF risk factors are associated with large hrQoL improvement, whereas less reversible conditions appeared negatively associated with hrQoL improvement. Understanding which patients are most likely to have large hrQoL improvement may facilitate targeting interventions for high-value care that optimizes patient-reported outcomes in AF. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01165710.

Detection of mutations in the rpoB gene of Mycobacterium tuberculosis can be used as an accurate predictor of rifampin resistance in the majority of strains tested. Simple but highly accurate screening methods must be developed for the detection of these mutations. Either DNA sequence analysis or single-strand conformation polymorphism (SSCP) screening can be used to detect rpoB mutations, but these techniques either are expensive or yield results that may prove difficult to interpret when used in a clinical setting. This report describes the use of dideoxy fingerprinting (ddF) as a postamplification screening method to identify rifampin-resistant genotypes. The ddF protocol was performed on the amplified rpoB fragment with no preparatory steps, thus making ddF practical for laboratories equipped for polyacrylamide gel electrophoresis. When compared with the results of SSCP analysis, ddF results were more easily interpreted and contained more sequence-dependent information that facilitated differentiation of functionally significant and silent mutations. The ddF method was used for genotypic determination of rifampin susceptibility of 20 multidrug-resistant strains of M. tuberculosis. The results of this analysis were concordant with DNA sequence analysis and conventional clinical laboratory methods.

Cellular therapies, such as stem cell–based treatments, have been widely researched and numerous products and treatments have been developed. Despite this, there has been relatively limited use of these technologies in the healthcare sector. This study sought to investigate the perceived barriers to this more widespread adoption. An anonymous online questionnaire was developed, based on the findings of a pilot study. This was distributed to an audience of clinicians, researchers and commercial experts in 13 countries. The results were analysed for all respondents, and also sub-grouped by geographical region, and by profession of respondents. The results of the study showed that the most significant barrier was manufacturing, with other factors such as efficacy, regulation and cost-effectiveness being identified by the different groups. This study further demonstrates the need for these important issues to be addressed during the development of cellular therapies to enable more widespread adoption of these treatments.

AbstractAlthough pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.

AbstractObjectiveDisparities in tobacco use persist despite successful policies reducing use within the United States. In particular, the prevalence of tobacco use in rural and certain minority communities is significantly higher compared to that of their counterparts. In this work, we examine the impact of rurality, mental health, and racial discrimination on tobacco use.MethodsData come from the 2003 California Health Interview Survey (n = 42,044). Modified Poisson regression models were adjusted for age, sex, race/ethnicity, birth origin, education, income, insurance, and marital status.ResultsCompared to urban residents, rural residents had a significantly higher risk for smoking after adjustment (RR = 1.10, 95% CI: 1.01‐1.19). Those who reported having experienced racial discrimination also had a significantly greater risk for smoking compared to those who did not (RR = 1.17, 95% CI: 1.07‐1.27). Additionally, those who reported higher stress had a significantly greater risk for smoking (RR = 1.61, 95% CI: 1.07‐1.67). There was evidence of interaction between rurality and race/ethnicity, and rurality and gender (P < .05).ConclusionResiding in rural areas was associated with an increased risk for smoking, above and beyond sociodemographics. There were no significant differences across rural‐urban environments for the relationship between stress and tobacco use—an indication that the impact of stress and discrimination is not buffered or exacerbated by environmental characteristics potentially found in either location. Mechanisms that explain rural‐urban tobacco use disparities need to be explored, and smoking cessation programs and policies should be tailored to target these factors within rural communities.

There has been a large increase in basic science activity in cell therapy and a growing portfolio of cell therapy trials. However, the number of industry products available for widespread clinical use does not match this magnitude of activity. We hypothesize that the paucity of engagement with the clinical community is a key contributor to the lack of commercially successful cell therapy products. To investigate this, we launched a pilot study to survey clinicians from five specialities and to determine what they believe to be the most significant barriers to cellular therapy clinical development and adoption. Our study shows that the main concerns among this group are cost-effectiveness, efficacy, reimbursement, and regulation. Addressing these concerns can best be achieved by ensuring that future clinical trials are conducted to adequately answer the questions of both regulators and the broader clinical community.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing—of expertise and/or funding—has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.

Background —The Bypass Angioplasty Revascularization Investigation (BARI) included 4039 patients with multivessel coronary artery disease; 1829 consented to randomization, and 2010 did not but were followed up in a registry. Thus, we can evaluate the outcome of physician-guided versus random assignment of percutaneous transluminal coronary angioplasty (PTCA) versus coronary artery bypass graft surgery (CABG). Methods and Results —We compared the baseline features and outcomes for PTCA and CABG in the overall registry and its predesignated subgroups. We assessed the impact of treatment by choice versus random assignment by comparing the results in the registry with those of the randomized trial. Statistical adjustments for differences in baseline characteristics were made. Within the registry, nearly twice as many patients were selected for PTCA (1189) as CABG (625); mortality at 7 years was similar for PTCA (13.9%) and CABG (14.2%) ( P =0.66) before and after adjustment for baseline differences between patients selected for PTCA versus CABG (adjusted RR, 1.02; P =0.86). In contrast to the randomized trial, the 7-year mortality rate of treated diabetics in the registry was equally high (26%) with PTCA or CABG. Seven-year mortality was higher for patients undergoing PTCA in the randomized trial than in the registry (19.1% versus 13.9%, P <0.01) but not for those undergoing CABG (15.6% versus 14.2%, P =0.57). The adjusted relative mortality risk for PTCA in the randomized versus registry population was 1.17 ( P =0.16). Conclusions —BARI physicians were able to select PTCA rather than CABG for 65% of registry patients who underwent revascularization without compromising long-term survival either in the overall population or in treated diabetics.

Background Cardiac mortality and myocardial infarction (MI) rates are used to evaluate the efficacy of coronary artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA). We compared 5-year cardiac mortality and MI rates in 1829 patients with multivessel disease randomized to CABG or PTCA. Methods and Results The 5-year cardiac mortality rate was 8.0% in patients assigned to PTCA compared with 4.9% in those assigned to CABG (relative risk [RR] of 1.55 with a 95% confidence interval [CI] of 1.07 to 2.23; P =.022). In a subgroup of 1476 nondiabetic patients, there were no significant differences between treatment groups in cardiac mortality either overall (4.6% versus 4.2%; RR=1.04, 95% CI, 0.65 to 1.66; P =.908) or in subgroups based on symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery. The two treatment groups had similar event rates for the combined end point of cardiac death or MI. The RR for cardiac mortality in 264 patients who sustained an MI compared with those who did not was 5.9 ( P <.001). MIs were more common after CABG during index hospitalization ( P =.004), but in the PTCA group, they were more common after discharge ( P <.001). Conclusions The Bypass Angioplasty Revascularization Investigation (BARI) trial indicates 5-year cardiac mortality in patients with multivessel disease was significantly greater after initial treatment with PTCA than with CABG. The difference was manifest in diabetic patients on drug therapy. There were no significant differences overall for the composite end point of cardiac mortality or MI between treatment groups or for cardiac mortality in nondiabetic patients regardless of symptoms, left ventricular function, number of diseased vessels, or stenotic proximal left anterior descending artery.