Miracle-dz/UniFAR-FTUs huggingface dataset:
Outcome Reporting Among Drug Trials Registered in ClinicalTrials.gov

BACKGROUND Clinical trial registries are in widespread use to promote transparency around trials and their results. OBJECTIVE To describe characteristics of drug trials listed in ClinicalTrials.gov and examine whether the funding source of these trials is associated with favorable published outcomes. DESIGN An observational study of safety and efficacy trials for anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors, and vasodilators conducted between 2000 and 2006. SETTING ClinicalTrials.gov, a Web-based registry of clinical trials launched in 1999. MEASUREMENTS Publications resulting from the trials for the 5 drug categories of interest were identified, and data were abstracted on the trial record and publication, including timing of registration, elements of the study design, funding source, publication date, and study outcomes. Assessments were based on the primary funding categories of industry, government agencies, and nonprofit or nonfederal organizations. RESULTS Among 546 drug trials, 346 (63%) were primarily funded by industry, 74 (14%) by government sources, and 126 (23%) by nonprofit or nonfederal organizations. Trials funded by industry were more likely to be phase 3 or 4 trials (88.7%; P < 0.001 across groups), to use an active comparator in controlled trials (36.8%; P = 0.010 across groups), to be multicenter (89.0%; P < 0.001 across groups), and to enroll more participants (median sample size, 306 participants; P < 0.001 across groups). Overall, 362 (66.3%) trials had published results. Industry-funded trials reported positive outcomes in 85.4% of publications, compared with 50.0% for government-funded trials and 71.9% for nonprofit or nonfederal organization-funded trials (P < 0.001). Trials funded by nonprofit or nonfederal sources with industry contributions were also more likely to report positive outcomes than those without industry funding (85.0% vs. 61.2%; P = 0.013). Rates of trial publication within 24 months of study completion ranged from 32.4% among industry-funded trials to 56.2% among nonprofit or nonfederal organization-funded trials without industry contributions (P = 0.005 across groups). LIMITATIONS The publication status of a trial could not always be confirmed, which could result in misclassification. Additional information on study protocols and comprehensive trial results were not available to further explore underlying factors for the association between funding source and outcome reporting. CONCLUSION In this sample of registered drug trials, those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources. PRIMARY FUNDING SOURCE National Library of Medicine and National Institute of Child Health and Human Development, National Institutes of Health.
National Institutes of Health State-of-the-Science Conference Statement: Preventing Alzheimer Disease* and Cognitive Decline

The National Institute on Aging and the Office of Medical Applications of Research of the National Institutes of Health convened a State-of-the-Science Conference on 26-28 April 2010 to assess the available scientific evidence on prevention of cognitive decline and Alzheimer disease. This article provides the panel's assessment of the available evidence.
Meta-analysis: Accuracy of Contrast-Enhanced Magnetic Resonance Angiography for Assessing Steno-occlusions in Peripheral Arterial Disease

BACKGROUND Contrast-enhanced magnetic resonance angiography (MRA) is a noninvasive, radiation-free imaging method for studying peripheral arterial disease (PAD) of the lower extremities. PURPOSE To summarize evidence of prospective studies about how well MRA identifies or excludes arterial steno-occlusions (50% to 100% lumen reduction) in adults with PAD symptoms. DATA SOURCES PubMed and 3 other databases were searched from 1998 to 2009 without language restrictions. STUDY SELECTION Two independent reviewers selected 32 studies that compared MRA with intra-arterial digital subtraction angiography in PAD. Eligible studies were prospective and provided data to reconstruct 2 x 2 or 3 x 3 contingency tables (<50% stenosis vs. > or =50% stenosis or occlusion of arterial segments) in at least 10 patients with PAD symptoms. DATA EXTRACTION Two reviewers independently assessed the study quality and extracted the study data, with disagreements resolved by consensus. DATA SYNTHESIS The 32 included studies generally had high methodological quality. About 26% of the 1022 included patients had critical limb ischemia with pain at rest or tissue loss. Overall, the pooled sensitivity of MRA was 94.7% (95% CI, 92.1% to 96.4%) and the specificity was 95.6% (CI, 94.0% to 96.8%) for diagnosing segmental steno-occlusions. The pooled positive and negative likelihood ratios were 21.56 (CI, 15.70 to 29.69) and 0.056 (CI, 0.037 to 0.083), respectively. Magnetic resonance angiography correctly classified 95.3%, overstaged 3.1%, and understaged 1.6% of arterial segments. LIMITATION Similar to most studies of computed tomographic angiography in PAD, the primary studies reported the diagnostic accuracy of MRA on a per-segment basis, not a per-patient basis. CONCLUSION This meta-analysis of 32 prospective studies further increases the evidence that contrast-enhanced MRA has high accuracy for identifying or excluding clinically relevant arterial steno-occlusions in adults with PAD symptoms. PRIMARY FUNDING SOURCE None.
Multicenter Validation of the Diagnostic Accuracy of a Blood-Based Gene Expression Test for Assessing Obstructive Coronary Artery Disease in Nondiabetic Patients

BACKGROUND Diagnosing obstructive coronary artery disease (CAD) in at-risk patients can be challenging and typically requires both noninvasive imaging methods and coronary angiography, the gold standard. Previous studies have suggested that peripheral blood gene expression can indicate the presence of CAD. OBJECTIVE To validate a previously developed 23-gene, expression-based classification test for diagnosis of obstructive CAD in nondiabetic patients. DESIGN Multicenter prospective trial with blood samples obtained before coronary angiography. (ClinicalTrials.gov registration number: NCT00500617) SETTING: 39 centers in the United States. PATIENTS An independent validation cohort of 526 nondiabetic patients with a clinical indication for coronary angiography. MEASUREMENTS Receiver-operating characteristic (ROC) analysis of classifier score measured by real-time polymerase chain reaction, additivity to clinical factors, and reclassification of patient disease likelihood versus disease status defined by quantitative coronary angiography. Obstructive CAD was defined as 50% or greater stenosis in 1 or more major coronary arteries by quantitative coronary angiography. RESULTS The area under the ROC curve (AUC) was 0.70 ± 0.02 (P < 0.001); the test added to clinical variables (Diamond-Forrester method) (AUC, 0.72 with the test vs. 0.66 without; P = 0.003) and added somewhat to an expanded clinical model (AUC, 0.745 with the test vs. 0.732 without; P = 0.089). The test improved net reclassification over both the Diamond-Forrester method and the expanded clinical model (P < 0.001). At a score threshold that corresponded to a 20% likelihood of obstructive CAD (14.75), the sensitivity and specificity were 85% and 43% (yielding a negative predictive value of 83% and a positive predictive value of 46%), with 33% of patient scores below this threshold. LIMITATION Patients with chronic inflammatory disorders, elevated levels of leukocytes or cardiac protein markers, or diabetes were excluded. CONCLUSION A noninvasive whole-blood test based on gene expression and demographic characteristics may be useful for assessing obstructive CAD in nondiabetic patients without known CAD. PRIMARY FUNDING SOURCE CardioDx.
The Affordable Care Act and the Future of Clinical Medicine: The Opportunities and Challenges

The Affordable Care Act is a once-in-a-generation change to the U.S. health system. It guarantees access to health care for all Americans, creates new incentives to change clinical practice to foster better coordination and quality, gives physicians more information to make them better clinicians and patients more information to make them more value-conscious consumers, and changes the payment system to reward value. The Act and the health information technology provisions in the American Recovery and Reinvestment Act remove many barriers to delivering high-quality care, such as unnecessary administrative complexity, inaccessible clinical data, and insufficient access to primary care and allied health providers. We hope that physicians will embrace the opportunities created by the Affordable Care Act that will enable them to provide better care for their patients and lead the U.S. health system in a more positive direction. To fully realize the benefits of the Affordable Care Act for their practices and their patients, physicians will design their offices for seamless care, employing new practice models and using technology to integrate patient information with professional society guidelines to keep patients with chronic conditions healthy and out of the hospital. Under the Affordable Care Act, physicians who effectively collaborate with other providers to improve patient outcomes, the value of medical services, and patient experiences will thrive and be the leaders of the health care system.
Advancing the Science for Active Surveillance: Rationale and Design for the Observational Medical Outcomes Partnership

The U.S. Food and Drug Administration (FDA) Amendments Act of 2007 mandated that the FDA develop a system for using automated health care data to identify risks of marketed drugs and other medical products. The Observational Medical Outcomes Partnership is a public-private partnership among the FDA, academia, data owners, and the pharmaceutical industry that is responding to the need to advance the science of active medical product safety surveillance by using existing observational databases. The Observational Medical Outcomes Partnership's transparent, open innovation approach is designed to systematically and empirically study critical governance, data resource, and methodological issues and their interrelationships in establishing a viable national program of active drug safety surveillance by using observational data. This article describes the governance structure, data-access model, methods-testing approach, and technology development of this effort, as well as the work that has been initiated.
A Systematic Examination of the Citation of Prior Research in Reports of Randomized, Controlled Trials

BACKGROUND A randomized, controlled trial (RCT) should not be started or interpreted without accounting for evidence from preceding RCTs addressing the same question. Research has suggested that evidence from prior trials is often not accounted for in reports of subsequent RCTs. OBJECTIVE To assess the extent to which reports of RCTs cite prior trials studying the same interventions. DESIGN Meta-analyses published in 2004 that combined 4 or more trials were identified; within each meta-analysis, the extent to which each trial report cited the trials that preceded it by more than 1 year was assessed. MEASUREMENTS The proportion of prior trials that were cited (prior research citation index), the proportion of the total participants from prior trials that were in the cited trials (sample size citation index), and the absolute number of trials cited were calculated. RESULTS 227 meta-analyses were identified, comprising 1523 trials published from 1963 to 2004. The median prior research citation index was 0.21 (95% CI, 0.18 to 0.24), meaning that less than one quarter of relevant reports were cited. The median sample size citation index (0.24 [CI, 0.21 to 0.27]) was similar, suggesting that larger trials were not selectively cited. Of the 1101 RCTs that had 5 or more prior trials to cite, 254 (23%) cited no prior RCTs and 257 (23%) cited only 1. The median number of prior cited trials was 2, which did not change as the number of citable trials increased. The mean number of preceding trials cited by trials published after 2000 was 2.4, compared with 1.5 for those published before 2000 (P < 0.001). LIMITATION The investigators could not ascertain why prior trials were not cited, and noncited trials may have been taken into account in the trial design and proposal stages. CONCLUSION In reports of RCTs published over 4 decades, fewer than 25% of preceding trials were cited, comprising fewer than 25% of the participants enrolled in all relevant prior trials. A median of 2 trials was cited, regardless of the number of prior trials that had been conducted. Research is needed to explore the explanations for and consequences of this phenomenon. Potential implications include ethically unjustifiable trials, wasted resources, incorrect conclusions, and unnecessary risks for trial participants. PRIMARY FUNDING SOURCE None.
Characteristics and Short-Term Prognosis of Perioperative Myocardial Infarction in Patients Undergoing Noncardiac Surgery

BACKGROUND Each year, millions of patients worldwide have a perioperative myocardial infarction (MI) after noncardiac surgery. OBJECTIVE To examine the characteristics and short-term outcome of perioperative MI. DESIGN Cohort study. (ClinicalTrials.gov registration number: NCT00182039) SETTING 190 centers in 23 countries. PATIENTS 8351 patients included in the POISE (PeriOperative ISchemic Evaluation) trial. MEASUREMENTS Four cardiac biomarker or enzyme assays were measured within 3 days of surgery. The definition of perioperative MI included either autopsy findings of acute MI or an elevated level of a cardiac biomarker or enzyme and at least 1 of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic changes on electrocardiography, coronary artery intervention, or cardiac imaging evidence of MI. RESULTS Within 30 days of random assignment, 415 patients (5.0%) had a perioperative MI. Most MIs (74.1%) occurred within 48 hours of surgery; 65.3% of patients did not experience ischemic symptoms. The 30-day mortality rate was 11.6% (48 of 415 patients) among patients who had a perioperative MI and 2.2% (178 of 7936 patients) among those who did not (P < 0.001). Among patients with a perioperative MI, mortality rates were elevated and similar between those with (9.7%; adjusted odds ratio, 4.76 [95% CI, 2.68 to 8.43]) and without (12.5%; adjusted odds ratio, 4.00 [CI, 2.65 to 6.06]) ischemic symptoms. LIMITATION Cardiac markers were measured only until day 3 after surgery, and additional asymptomatic MIs may have been missed. CONCLUSION Most patients with a perioperative MI will not experience ischemic symptoms. Data suggest that routine monitoring of troponin levels in at-risk patients is needed after surgery to detect most MIs, which have an equally poor prognosis regardless of whether they are symptomatic or asymptomatic.
Risk Factors and Other Epidemiologic Considerations for Cervical Cancer Screening: A Narrative Review for the U.S. Preventive Services Task Force

Despite the success of cervical cancer screening programs, questions remain about the appropriate time to begin and end screening. This review explores epidemiologic and contextual data on cervical cancer screening to inform decisions about when screening should begin and end. Cervical cancer is rare among women younger than 20 years. Screening for cervical cancer in this age group is complicated by lower rates of detection and higher rates of false-positive results than in older women. Methods used to diagnose and treat cervical intraepithelial neoplasia have important potential adverse effects. High-risk human papillomavirus infections and abnormalities on cytologic and histologic examination have relatively high rates of regression. Accordingly, cervical cancer screening in women younger than 20 years may be harmful. The incidence of, and mortality rates from, cervical cancer and the proportion of U.S. women aged 65 years or older who have had a Papanicolaou smear within 3 years have decreased since 2000. Available evidence supports discontinuation of cervical cancer screening among women aged 65 years or older who have had adequate screening and are not otherwise at high risk. Further reductions in the burden of cervical cancer in older women are probably best achieved by focusing on screening those who have not been adequately screened.
CARBONATED DRINKS - CAN OF POISON

In 2007 the worldwide annual consumption of soft drinks reached 552 billion litres, the equivalent of just under 83 litres per person per year, and this is projected to increase to 95 litres per person per year by 2012. Undernutrition and infections had been the major causes of morbidity and mortality in developing countries like India. But today's scenario suggests the emergence of degenerative diseases is likely to be due to overnutrition or obesity. Youngsters consume soft drinks at a breath taking speed. Long term consumption of soft drinks has lead to a number of health issues that have already been, identified including tooth problems, bone demineralization and the development of metabolic syndrome, and diabetes. There was a noticeable preference among the youth for junk foods, aerated beverages and ice creams, as evident from the food frequency pattern. One of the channels used by industry to encourage greater consumption and preferences for soft drinks is schools, fast food centers, etc. But governments around the world are taking action to limit the availability of soft drinks in such places. Policies vary in ways too, presenting an opportunity to study the effects of different policy approaches on short-and long-term consumption and attitudes towards these soft drinks.
GOUT: THE KING OF DISEASES AND THE DISEASE OF KINGS

Gout is a metabolic disorder caused by hyperuricemia resulting in joints and other tissues deposition of urate crystals. Clinical manifestation includes recurrent attacks of arthritis and accumulation of crystalline deposits called tophi. Gout is considered a progressive disease that, without long-term treatment, can progress to severe tophaceous gout. The disease is increasing in prevalence as a result of changes in diet, lifestyle and environmental factors. Hyperuricemia has a fundamental role as risk factor in the development of gout and seems also to be a risk factor for some comorbidities. The goal of the treatment of gout is to reduce serum uric acid levels sufficiently that crystals can no longer form. A future research agenda should include the identification of genes associated with risk for gout and the development of new urate lowering drugs with a specific target. In the next future, controlled studies are also required to understand the significance and the underlying mechanism of the association between hyperuricemia and some comorbidities.
Risk for Hepatocellular Carcinoma in Patients With Alcoholic Cirrhosis

BACKGROUND Patients with alcoholic cirrhosis are at higher risk for hepatocellular carcinoma (HCC). The role of HCC surveillance for these patients is undefined. OBJECTIVE To provide population-based estimates of HCC incidence and comparisons of HCC-related mortality and total mortality among patients with alcoholic cirrhosis as a basis for assessing the role of HCC surveillance. DESIGN Nationwide, registry-based, historical cohort study. SETTING Denmark. PATIENTS All Danish citizens with a first-time hospital diagnosis of alcoholic cirrhosis from 1993 to 2005. MEASUREMENTS Hepatocellular carcinoma incidence and mortality starting 1 year after diagnosis of alcoholic cirrhosis through 2009; ratio of HCC-related mortality to total mortality. RESULTS Among 8482 patients, 169 developed HCC. A total of 5734 patients died, 151 of whom had developed HCC. Five-year cumulative HCC risk was 1.0% (95% CI, 0.8% to 1.3%), and 5-year cumulative mortality was 43.7% (CI, 42.6% to 44.7%). Only 1.8% of all deaths were HCC-related. In sensitivity analyses that included all possible HCC diagnoses and a subpopulation of patients who were followed by hepatologists, the highest 5-year HCC risk was 1.9% (CI, 0.8% to 3.9%). These patients did not have higher mortality than patients in the nationwide cohort. LIMITATION Cirrhosis and HCC diagnoses were made by hospital physicians without uniform clinical criteria, and use of registry data precluded detailed information on clinical care of patients, including HCC surveillance. CONCLUSION Danish patients with alcoholic cirrhosis have a low risk for HCC, and HCC contributes little to their high mortality. On the basis of these data, HCC surveillance would be expected to have a minimal effect on mortality and is unlikely to be cost-effective.
Adverse Outcomes After Hospitalization and Delirium in Persons With Alzheimer Disease

BACKGROUND Hospitalization, frequently complicated by delirium, can be a life-changing event for patients with Alzheimer disease (AD). OBJECTIVE To determine risks for institutionalization, cognitive decline, or death associated with hospitalization and delirium in patients with AD. DESIGN Prospective cohort enrolled between 1991 and 2006 into the Massachusetts Alzheimer's Disease Research Center (MADRC) patient registry. SETTING Community-based. PARTICIPANTS 771 persons aged 65 years or older with a clinical diagnosis of AD. MEASUREMENTS Hospitalization, delirium, death, and institutionalization were identified through administrative databases. Cognitive decline was defined as a decrease of 4 or more points on the Blessed Information-Memory-Concentration test score. Multivariate analysis was used to calculate adjusted relative risks (RRs). RESULTS Of 771 participants with AD, 367 (48%) were hospitalized and 194 (25%) developed delirium. Hospitalized patients who did not have delirium had an increased risk for death (adjusted RR, 4.7 [95% CI, 1.9 to 11.6]) and institutionalization (adjusted RR, 6.9 [CI, 4.0 to 11.7]). With delirium, risk for death (adjusted RR, 5.4 [CI, 2.3 to 12.5]) and institutionalization (adjusted RR, 9.3 [CI, 5.5 to 15.7]) increased further. With hospitalization and delirium, the adjusted RR for cognitive decline for patients with AD was 1.6 (CI, 1.2 to 2.3). Among hospitalized patients with AD, 21% of the incidences of cognitive decline, 15% of institutionalization, and 6% of deaths were associated with delirium. LIMITATIONS Cognitive outcome was missing in 291 patients. Sensitivity analysis was performed to test the effect of missing data, and a composite outcome was used to decrease the effect of missing data. CONCLUSION Approximately 1 in 8 hospitalized patients with AD who develop delirium will have at least 1 adverse outcome, including death, institutionalization, or cognitive decline, associated with delirium. Delirium prevention may represent an important strategy for reducing adverse outcomes in this population.