Clinical Trials Series: Comparative Effectiveness Studies and Patient Care
Clinical trials of interventions in common practice can be built into the workflow of an electronic medical record. The ...authors review four such trials and highlight the strengths and weaknesses of this approach to gathering information.
Clinical trials that are embedded into usual care have the potential to yield outcomes of great relevance to the institutions where they are performed and at the same time to yield information that may be generalizable to the health care system at large. In this article, we review four clinical trials that were conducted in three health care systems using their extant electronic health record (EHR) systems. We find that EHR-based clinical trials are feasible but pose limitations on the questions that can be addressed, the processes that can be implemented, and the outcomes that can be assessed. We think . . .
Patients 65 or older with hypertension who switched from hydrochlorothiazide to chlorthalidone did not have fewer major cardiovascular events or non–cancer-related deaths than those who continued ...receiving hydrochlorothiazide.
Adverse Events Associated with Testosterone Administration Basaria, Shehzad; Coviello, Andrea D; Travison, Thomas G ...
New England journal of medicine/The New England journal of medicine,
07/2010, Letnik:
363, Številka:
2
Journal Article
Recenzirano
Odprti dostop
In a randomized trial, men 65 years of age or older who had low serum testosterone levels and limitations in mobility were assigned to either placebo or testosterone gel to be applied daily for 6 ...months. The primary end point was improvement in leg-press strength, which was greater with testosterone therapy than with placebo. However, the trial was stopped early because of a greater number of cardiac adverse events in the testosterone group.
In men 65 years of age or older with low serum testosterone levels and limitations in mobility, improvement in leg-press strength was greater with testosterone therapy than with placebo. However, there were more cardiac adverse events in the testosterone group.
Limited mobility is a common geriatric condition that is a predictor of disability, poor quality of life, and death.
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In men, an age-related decline in the serum testosterone concentration is associated with reduced muscle mass and lower-extremity strength, limitations in physical function, and poor mobility.
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Testosterone supplementation increases muscle mass and strength and leg power, all of which are important determinants of mobility.
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Previous trials of testosterone supplementation have been conducted primarily among healthy older men. The safety and efficacy of testosterone treatment in improving muscle performance and physical function in older men with limitations in mobility . . .
After the acute coronary syndrome, adding warfarin to standard aspirin therapy decreases myocardial infarction and stroke but increases major bleeding.
To quantify the risks and benefits of warfarin ...therapy after the acute coronary syndrome.
MEDLINE from 1990 to October 2004. Additional data were obtained from study authors. Clinical risk factors were used to classify hypothetical patients into cardiovascular and bleeding risk groups on the basis of published data.
Randomized trials comparing intensive warfarin therapy (international normalized ratio > 2.0) plus aspirin with aspirin alone after the acute coronary syndrome.
Two reviewers independently selected studies and extracted data on study design; quality; and clinical outcomes, including myocardial infarction, stroke, revascularization, death, and major and minor bleeding. Rate ratios for outcomes were calculated and pooled by using the method of DerSimonian and Laird.
Ten trials involving a total of 5938 patients (11,334 patient-years) met the study criteria. Compared with aspirin alone, warfarin plus aspirin was associated with a decrease in the annual rate of myocardial infarction (0.022 vs. 0.041; rate ratio, 0.56 95% CI, 0.46 to 0.69), ischemic stroke (0.004 vs. 0.008; rate ratio, 0.46 CI, 0.27 to 0.77), and revascularization (0.115 vs. 0.135; rate ratio, 0.80 CI, 0.67 to 0.95). Warfarin was associated with an increase in major bleeding (0.015 vs. 0.006; rate ratio, 2.5 CI, 1.7 to 3.7). Mortality did not differ.
Two large studies provided most of the data. Studies did not include coronary stenting, and results should not be applied to patients with stents. Relative risk reductions may not be consistent across risk groups.
For patients with the acute coronary syndrome who are at low or intermediate risk for bleeding, the cardiovascular benefits of warfarin outweigh the bleeding risks.
Abstract Hospitalizations for acute decompensated heart failure (ADHF) is an important outcome in clinical trials and heart failure registries; however the optimal strategy to identify these ...hospitalizations using International Classification of Diseases Ninth Revision (ICD-9) codes is uncertain. We sought to identify diagnostic codes that improve ascertainment of ADHF hospitalizations. Heart failure related ICD-9 principal discharge codes were used to identify 2,202 hospitalizations within the Minneapolis Veterans Affairs (VA) Medical Center between 2009 and 2014. Two independent reviewers adjudicated 447 of these hospitalizations to determine the accuracy of each code. We then applied our findings to an unadjusted nationwide sample containing the same ICD-9 codes of interest, from which overall positive predictive value (PPV), sensitivity, and accuracy were calculated. Use of 428.x alone resulted in a PPV of 91.3% (95% CI: 91.0-91.7), sensitivity of 97.5% (95% CI: 97.3-97.6), and accuracy of 89.7% (95% CI: 89.4-90.0). Combining 428.x with 402.x1, 404.x1, 415, and 518.4 resulted in improved sensitivity 99.2% (95% CI: 99.0-99.3) and accuracy 90.7% (95% CI: 90.4-91.1) while maintaining a PPV of 91.1% (95% CI: 90.7-91.4). Excluding chronic heart failure codes (428.22, 428.32, 428.42) from the proposed strategy resulted in an improvement of PPV to 92.3% (95% CI: 92.0-92.6), though sensitivity and accuracy decreased to 96.6% (95% CI: 96.3-96.8) and 90.0% (95% CI: 89.6-90.3), respectively. In conclusion, a combination of codes including 428.x, 402.x1, 404.x1, 415, and 518.4 improves sensitivity and overall accuracy in ascertaining ADHF events when compared to 428.x alone. This strategy could be further improved by manual adjudication of chronic heart failure codes.
Background Meta-analyses of trials of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors or statins for cardiovascular disease prevention have failed to show any statistically significant benefit ...of statins for cancer prevention. However, these trials included relatively young participants, who develop few cancers, and their follow-up periods may have been too short to detect an association between statin use and cancer incidence. We investigated this association in a population of veterans. Methods We identified patients using antihypertensive medications but no cholesterol-lowering medications (n = 25594) and patients using statins (n = 37248) who were enrolled in the Veterans Affairs New England Healthcare System between January 1, 1997, and December 31, 2005. Age- and multivariable-adjusted Cox proportional hazards models were used to calculate the hazard ratio (HR) and its 95% confidence interval (CI) for cancer incidence, excluding nonmelanoma skin cancer, among patients taking statins compared with patients taking antihypertensive medications and among patients grouped by statin dose (as equivalent simvastatin dose). All statistical tests were two-sided. Results The absolute incidence of total cancers was 9.4% among statin users and 13.2% among nonusers (difference = 3.8%, 95% CI = 3.3% to 4.3%, Pdifference < .001). Statin users had a statistically significant lower risk for total cancer than nonusers after adjustment for age (HR = 0.76, 95% CI = 0.73 to 0.80) and multiple potential confounders (HR = 0.74, 95% CI = 0.70 to 0.78). After multivariable adjustment, a statistically significantly decreased risk of all cancers was also associated with increasing statin use (Ptrend < .001). Conclusions Patients using statins may be at lower risk for developing cancer. Additional observational studies and randomized trials of statins for cancer prevention are warranted.
Background. Observational studies linking proton pump inhibitor (PPI) exposure with community-acquired pneumonia (CAP) have reported either modest or no associations. Accordingly, we studied PPI ...exposure and CAP in veteran patients, using a retrospective, nested case-control design. Methods. From linked pharmacy and administrative databases of the New England Veterans Healthcare System, we identified 71985 outpatients newly prescribed PPIs between 1998 and 2007; 1544 patients met criteria for CAP subsequent to PPI initiation; 15440 controls were matched through risk-set sampling by age and time under observation. Crude and adjusted odds ratios comparing current with past PPI exposures, as well as tests for interactions, were conducted for the entire and stratified samples. Results. Current PPI use associated with CAP (adjusted odds ratio OR, 1.29 95% confidence interval {CI}, 1.15-1.45). Risks were not substantially altered by age or year of diagnosis. Dementia (n = 85; P = .062 for interaction) and sedative/tranquilizer use (n = 224; P = .049 for interaction) were likely effect modifiers increasing a PPI-CAP association; conversely, for some chronic medical conditions, PPI-associated CAP risks were reversed. PPI exposures between 1 and 15 days increased CAP risks, compared with longer exposures, but PPI initiation also frequently occurred shortly after CAP diagnoses. Prescribed PPI doses > 1 dose/day also increased PPI-associated CAP risks. Conclusions. Among the veterans studied, current compared with past PPI exposures associated modestly with increased risks of CAP. However, our observations that recent treatment initiation and higher PPI doses were associated with greater risks, and the inconsistent PPI-CAP associations between patient subgroups, indicate that further inquiries are needed to separate out coincidental patterns of associations.
Thrombosis of hemodialysis vascular access grafts represents a major medical and economic burden. Experimental and clinical models suggest a role for antiplatelet agents in the prevention of ...thrombosis. The study was designed to determine the efficacy of the combination of aspirin and clopidogrel in the prevention of graft thrombosis. The study was a randomized, double-blind trial conducted at 30 hemodialysis units at Veterans Affairs medical centers. Participants undergoing hemodialysis with a polytetrafluoroethylene graft in the arm were randomized to receive either double placebos or aspirin (325 mg) and clopidogrel (75 mg) daily. Participants were to be monitored while receiving study medications for a minimum of 2 yr. The study was stopped after randomization of 200 participants, as recommended by the Data Safety and Monitoring Board because of a significantly increased risk of bleeding among the participants receiving aspirin and clopidogrel therapy. The cumulative incidence of bleeding events was significantly greater for those participants, compared with participants receiving placebos hazard ratio, 1.98; 95% confidence interval (CI), 1.19 to 3.28; P = 0.007. Twenty-three participants in the placebo group and 44 participants in the active treatment group experienced a bleeding event (P = 0.006). There was no significant benefit of active treatment in the prevention of thrombosis (hazard ratio, 0.81; 95% CI, 0.47 to 1.40; P = 0.45), although there was a trend toward a benefit among participants who had not experienced previous graft thrombosis (hazard ratio, 0.52; 95% CI, 0.22 to 1.26; P = 0.14). In the hemodialysis population, therapy with aspirin and clopidogrel was associated with a significantly increased risk of bleeding and probably would not result in a reduced frequency of graft thrombosis.
The analysis of big healthcare data has enormous potential as a tool for advancing oncology drug development and patient treatment, particularly in the context of precision medicine. However, there ...are challenges in organizing, sharing, integrating, and making these data readily accessible to the research community. This review presents five case studies illustrating various successful approaches to addressing such challenges. These efforts are CancerLinQ, the American Association for Cancer Research Project GENIE, Project Data Sphere, the National Cancer Institute Genomic Data Commons, and the Veterans Health Administration Clinical Data Initiative. Critical factors in the development of these systems include attention to the use of robust pipelines for data aggregation, common data models, data deidentification to enable multiple uses, integration of data collection into physician workflows, terminology standardization and attention to interoperability, extensive quality assurance and quality control activity, incorporation of multiple data types, and understanding how data resources can be best applied. By describing some of the emerging resources, we hope to inspire consideration of the secondary use of such data at the earliest possible step to ensure the proper sharing of data in order to generate insights that advance the understanding and the treatment of cancer.
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