EMBARGOED FOR EARLY RELEASE: 1 A.M. (CT) MONDAY, AUGUST 27, 2012

Media Advisory: To contact corresponding author Nicolas Danchin, M.D., Ph.D., email nicolas.danchin@egp.aphp.fr.

CHICAGO – The overall rate of death in patients hospitalized with ST-segment elevation myocardial infarction (STEMI; a certain pattern on an electrocardiogram following a heart attack) decreased from 1995 to 2010 in France, with possible factors associated with this decline including an increase in the proportion of STEMI patients who were women younger than age 60, and an increase in the use of reperfusion therapy and recommended therapeutic measures following a heart attack, according to a study being published online by JAMA. The study is being released early to coincide with its presentation at the European Society of Cardiology Congress.

“Several sources, including registries specific to acute myocardial infarction [AMI; heart attack] and large administrative or billing databases, have shown a decrease in mortality in patients with STEMI over the past 10 to 15 years. This decline is usually attributed to increased use and improved delivery of reperfusion therapy, in particular primary percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries). We hypothesized that, beyond primary PCI, other factors such as temporal changes in patient population characteristics may account for part of the observed reduction in mortality of patients with STEMI,” the authors write.

Etienne Puymirat, M.D., of the Hôpital Européen Georges Pompidou, Paris, and colleagues conducted a study to assess the association between changes in early mortality following STEMI and patient management and risk profile. The researchers analyzed data from four 1-month French nationwide registries, conducted 5 years apart (in 1995, 2000, 2005 and 2010), which included a total of 6,707 STEMI patients admitted to intensive care or coronary care units.

During the study period, the average age of patients with STEMI declined from 66.2 years to 63.3 years, and history of cardiovascular disease, such as heart attack, heart failure, peripheral artery disease, stroke or transient ischemic attack also decreased. The proportion of younger women (60 years or less) with STEMI increased from 11.8 percent to 25.5 percent, consistent with their increased prevalence of smoking (from 37.3 percent to 73.1 percent) and obesity (from 17.6 percent to 27.1 percent). The proportion of younger patients developing STEMI despite not having hypertension, diabetes, or hypercholesterolemia increased markedly, particularly in younger women.

The authors also found that the use of reperfusion therapy increased over time, from 49.4 percent to 74.7 percent, with more frequent use of primary PCI, (11.9 percent to 60.8 percent). The use of evidence-based treatments during the first 48 hours from admission increased gradually over the 15-year period, including the early use of b-blockers, ACE inhibitors or angiotensin-receptor blockers, and statins. Also, there was increasing early use of antiplatelet agents and low-molecular-weight heparins.

Thirty-day mortality decreased from 13.7 percent in 1995 to 4.4 percent in 2010; mortality decreased from 9.8 percent to 2.6 percent in men and from 23.7 percent to 9.8 percent in women. Consistent with the decrease in mortality, major hospital complications of STEMI also decreased over this time period.

In addition, time from symptom onset to hospital admission decreased, with a shorter time from onset to first call, and broader use of mobile intensive care units.

“The progressive decline in early mortality over time observed in the present nationwide surveys is consistent with many other sources in the United States and Europe,” the authors note.

“Within the STEMI population targeted by these sequential registries, the relative proportion of older patients has decreased, while the proportion of younger men and the proportion and numbers of younger women have increased. These observations suggest that future reductions in the incidence and mortality related to AMI will need specific targeting of preventive measures toward younger women and possibly younger men.”

(doi:10.1001/2012.jama.11348. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR EARLY RELEASE: 1 A.M. (CT) SUNDAY, AUGUST 26, 2012

Media Advisory: To contact James K. Min, M.D., call Sally Stewart at 310-423-4768 or email sally.stewart@cshs.org. To contact editorial author Manesh R. Patel, M.D., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

CHICAGO – Among patients with suspected or known coronary artery disease, use of a method that applies computational fluid dynamics to derive certain data from computed tomographic (CT) angiography demonstrated improved diagnostic accuracy vs. CT angiography alone for the diagnosis of ischemia, according to a study being published online by JAMA. The study is being released early to coincide with its presentation at the European Society of Cardiology Congress.

“Coronary computed tomographic angiography is a noninvasive anatomic test for diagnosis of coronary stenosis [narrowing of a blood vessel] that does not determine whether a stenosis causes ischemia [inadequate blood supply]. In contrast, fractional flow reserve (FFR) is a physiologic measure of coronary stenosis expressing the amount of coronary flow still attainable despite the presence of a stenosis, but it requires an invasive procedure. Noninvasive FFR computed from CT (FFR_CT) is a novel method for determining the physiologic significance of coronary artery disease (CAD), but its ability to identify ischemia has not been adequately examined to date,” according to background information in the article.

James K. Min, M.D., of the Cedars-Sinai Heart Institute, Los Angeles, and colleagues conducted a study to evaluate the performance of noninvasive FFR_CT compared with an invasive FFR reference standard for diagnosis of ischemia. The study included 252 patients with suspected or known CAD from 17 centers in 5 countries who underwent CT, invasive coronary angiography (ICA), FFR, and FFR_CT between October 2010 and October 2011. About 77 percent of patients had experienced angina within the last month. Ischemia was defined by certain criteria. Anatomically obstructive CAD was defined by a stenosis of 50 percent or larger on CT and ICA. Among 615 study vessels, 271 had less than 30 percent stenosis and 101 had at least 90 percent stenosis.

Among study participants, 137 (54.4 percent) had an abnormal FFR as determined by ICA. The researchers found that the diagnostic accuracy for FFR_CT plus CT was 73 percent, which did not meet a prespecified primary end point for accuracy (as pre-specified based on the lower limit of a calculated 95 percent confidence interval). By comparison, diagnostic accuracy of CT alone for detecting coronary lesions with stenosis of 50 percent or greater, was 64 percent. When comparing FFR_CT alone with CT alone for detecting these lesions, FFR_CT demonstrated superior discrimination.

“On a per-patient basis, diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of FFR_CT plus CT were 73 percent, 90 percent, 54 percent, 67 percent, and 84 percent, respectively,” the authors write. They note that the sensitivity and negative predictive value of FFR_CT were high, indicating a low rate of false-negative studies. “These diagnostic features of FFR_CT may encourage a greater sense of diagnostic certainty that patients who undergo CT who have ischemia are not overlooked, such that clinicians may be confident in not proceeding to invasive angiography in patients with stenoses on CT when FFR_CT results are normal.”

“Taken together, these study results suggest the potential of FFR_CT as a promising noninvasive method for identification of individuals with ischemia.”

(doi:10.1001/2012.jama.11274. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This study was funded by HeartFlow Inc. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Detecting Obstructive Coronary Disease With CT Angiography and Noninvasive Fractional Flow Reserve

In an accompanying editorial, Manesh R. Patel, M.D., of Duke University Medical Center, Durham, N.C., writes that future studies with the FFR_CT technology “should be aimed at diagnostic strategies involving patients with varying pretest risks, thereby providing information on the incremental benefit from the test.”

“Additionally, important comparison technologies beyond invasive angiography are needed, although improved access techniques and safety of invasive FFR may make it a plausible comparator. In addition to diagnostic performance, other outcomes of interest such as resource utilization and clinical outcomes should be captured. Finally, future studies will need to have local sites rather than core laboratories perform, analyze, and interpret the images to provide a sense of real-world function. It is with these types of continued rigorous studies that noninvasive technologies such as FFR_CT plus CT may move the clinical community closer to the holy grail of a high-quality combined anatomic and functional test for detection of CAD that improves efficiency and patient outcomes.”

(doi:10.1001/2012.jama.11383. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 21, 2012

Preventing Patient Harms Through Systems of Care

Peter J. Pronovost, M.D., Ph.D., of the Johns Hopkins Medical Institutions, Baltimore, and George W. Bo-Linn, M.D., M.H.A., of the Gordon and Betty Moore Foundation, Palo Alto, Calif., discuss the problem of preventable harms to patients, which include adverse drug events, catheter-associated urinary tract infections, central line-associated bloodstream infections, and pressure ulcers. The authors suggest “clinicians can reduce patient harm in the same way that engineers manage dynamic complexity: as a systems problem that requires an interdisciplinary systems solution.”

“It is time for the science of health care delivery to mature and embrace systems engineering. It is time for health care to embrace the compelling goal of reducing preventable patient harm. By systematically addressing all the known harms patients may experience, clinicians may realize this goal and, by doing so, improve health care and reduce costs of care, ultimately improving value for the nation and its citizens.”

(JAMA. 2012;308[8]:769-770. Available pre-embargo to the media at http://media.jamanetwork.com)

Transforming Quality of Care and Improving Outcomes After Acute Ml – Lessons From the National Registry of Myocardial Infarction

William J. French, M.D., of the Harbor-UCLA Medical Center, Torrance, Calif., and colleagues write that the “National Registry of Myocardial Infarction (NRMI) was the leading cardiovascular disease (CVD) patient registry from 1990 to 2006 in both size and duration. Notably, the various analyses and publications that resulted from the NRMI had direct and substantial effects in improving quality care for acute myocardial infarction treatment in the United States.” In this Viewpoint, the authors discuss the history of the NRMI, and building on the NRMI model.

“As health care practice and treatment options evolve, patient registries remain an important tool for evaluating the interface among patients, physicians, and sites of care. The NRMI was a remarkable achievement and unexpectedly successful in transforming CVD care, in part because it set a high standard for observational research and met an emerging need in the U.S. health care system. The legacy of the NRMI is a model to build upon.”

(JAMA. 2012;308[8]:771-772. Available pre-embargo to the media at http://media.jamanetwork.com)

The Value of Statistical Analysis Plans in Observational Research – Defining High-Quality Research From the Start

Laine Thomas, Ph.D., of the Duke University School of Medicine, Durham, N.C., and Eric D. Peterson, M.D., M.P.H., of the Duke Clinical Research Institute, and Contributing Editor, JAMA, suggest that there needs to be improvement in defining standards for reporting observational research, and that “the concepts for improving observational research can be operationalized via use of a formal, prospectively defined statistical analysis plan (SAP).” The authors discuss the development and potential benefits of the use of an SAP.

“The process of writing and submitting an SAP captures many of the attributes of clinical trials, without excessive rigidity that would inhibit exploratory research. It requires extra work on the front end but greater efficiency and clarity in producing and reporting results. Current practice may be augmented by making the SAP publicly available as online ancillary material. This would allow readers to confirm and, if desired, replicate the methods used in the study.”

(JAMA. 2012;308[8]:773-774. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 21, 2012

Media Advisory: To contact co-author Michiel L. Bots, M.D., Ph.D., email m.l.bots@umcutrecht.nl.

CHICAGO – In an analysis of data from previously published studies that included more than 45,000 patients, the value of adding to the Framingham Risk Score a measure of the common carotid artery intima-media thickness (CIMT; a measurement of the thickness of the carotid artery wall) in 10-year risk prediction of first-time heart attack or stroke was small and unlikely to be of clinical importance, according to an article in the August 22/29 issue of JAMA.

“Cardiovascular disease is among the leading causes of morbidity and mortality worldwide. Preventive treatment of high-risk asymptomatic individuals depends on accurate prediction of a person’s risk to develop a cardiovascular event. Currently, cardiovascular risk prediction in asymptomatic individuals is based on the level of cardiovascular risk factors incorporated in scoring equations. Several scores are available, with the Framingham Risk Score (FRS) among the most widely used. These risk equations perform reasonably well, yet there remains considerable overlap in estimated risk between those who are affected by a cardiovascular event and those who are not,” according to background information in the article.

Measurement of CIMT has been proposed to be added to cardiovascular risk factors to improve individual risk assessment. “So far, individual studies reported on the added value of CIMT measurements in cardiovascular risk prediction, but the evidence is not consistent across studies,” the authors write.

Hester M. Den Ruijter, Ph.D., of the University Medical Center Utrecht, the Netherlands, and colleagues conducted a meta-analysis to determine whether common CIMT has added value in 10-year risk prediction of first-time heart attacks or strokes, above that of the Framingham Risk Score. The authors searched the medical literature and identified relevant studies for inclusion in the analysis. Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time heart attack or stroke.

This analysis included 14 studies contributing data for 45,828 individuals. During a median (midpoint) follow-up of 11 years, 4,007 first-time heart attacks or strokes occurred. The researchers refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time heart attack or stroke in both models. More than 90 percent of the individuals remained in the same risk category. The numbers of individuals shifting downward or upward without and with events were similar. The net reclassification improvement with the addition of common CIMT was small (0.8 percent were correctly reclassified). In those at intermediate risk, the net reclassification improvement was 3.6 percent in all individuals, with no differences between men and women.

“Our results suggest that common CIMT measurements should not routinely be performed in the general population, as the overall added value may be too limited to result in health benefits,” the authors write. “However, as the interest in risk prediction is currently shifting from a 10-year risk to lifetime risk, the added value of a CIMT measurement and its cost-effectiveness using a horizon of 20 to 30 years may be worthwhile to explore.”

(JAMA. 2012;308[8]:796-803. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This project is supported by a grant from the Netherlands Organisation for Health Research and Development. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 21, 2012

Media Advisory: To contact David Preiss, M.D., Ph.D., email david.preiss@glasgow.ac.uk.

CHICAGO – Although some studies have suggested that use of lipid-lowering therapies may increase the risk of pancreatitis, an analysis that involved pooling of data from previous studies and included more than 150,000 participants found that statin therapy was associated with a reduction in the risk of pancreatitis in patients with normal or mildly elevated triglyceride levels, according to an article in the August 22/29 issue of JAMA.

“Pancreatitis has a clinical spectrum ranging from a mild, self-limiting episode to a severe or fatal event. Case reports and pharmacoepidemiology studies have claimed that statins may cause pancreatitis, although few of these studies comprehensively considered confounding factors. Very few large randomized trials of statin therapy have published data on incident pancreatitis,” according to background information in the article. “Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis.”

David Preiss, M.D., Ph.D., of the University of Glasgow, United Kingdom, and colleagues examined the associations between use of a statin or a fibrate and the incidence of pancreatitis by conducting collaborative meta-analyses of published and unpublished data from large randomized clinical trials. The authors conducted a search of the medical literature to identify relevant studies for inclusion in the analysis.

In 16 placebo- and standard care-controlled statin trials with 113,800 participants conducted over 4.1 years, 309 participants (0.27 percent) developed pancreatitis (134 assigned to statin, 175 assigned to control; a 23 percent lower risk of pancreatitis for those assigned to statin therapy). In 5 dose-comparison statin trials with 39,614 participants conducted over 4.8 years, 156 participants (0.39 percent) developed pancreatitis (70 assigned to intensive dose, 86 assigned to moderate dose; an 18 percent lower risk for the intensive dose group).

In the combined data set of 21 trials, 465 participants (0.30 percent) developed pancreatitis (of whom 204 were assigned to statin therapy or intensive-dose statin therapy and 261 were assigned to placebo, standard care, or moderate-dose statin therapy, respectively), a 21 percent lower risk.

Seven randomized clinical trials of fibrate therapy (4 with published data and 3 with unpublished data regarding incident pancreatitis) provided data on 40,162 participants over a weighted average follow-up period of 5.3 years. Baseline average triglyceride levels in the trials varied from 145 mg/dL to 184 mg/dL. During this time, 144 participants (0.36 percent) developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo), but the risk difference was not statistically significant.

“Although the present results for both statins and fibrates should be considered hypothesis-generating and the number of pancreatitis cases was small in this trial population at low risk of pancreatitis, the analysis raises questions regarding the choice of lipid-modifying agents in patients with hypertriglyceridemia. In those with slightly elevated triglyceride levels, statins appear better supported by the available data than fibrates for preventing pancreatitis. Lifestyle modifications also remain important to improve lipid profiles in such individuals. In patients with severe hypertriglyceridemia, a trial comparing fibrates and statins for preventing pancreatitis would be clinically valuable,” the authors write.

(JAMA. 2012;308[8]:804-811. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This project was not supported by external funding. Dr. Welsh is supported by a British Heart Foundation fellowship grant. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 21, 2012

Media Advisory: To contact corresponding author Stephan Windecker, M.D., email stephan.windecker@insel.ch. To contact editorial co-author Adnan Kastrati, M.D., email kastrati@dhm.mhn.de.

CHICAGO – Compared with a bare-metal stent, the use of a stent with a biodegradable polymer that releases the drug biolimus resulted in a lower rate of major adverse cardiac events at 1 year among patients with ST-segment elevation myocardial infarction (STEMI; a certain pattern on an electrocardiogram following a heart attack) undergoing primary percutaneous coronary intervention (PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries), according to a study in the August 22/29 issue of JAMA.

“The efficacy and safety of drug-eluting [releasing] stents compared with bare-metal stents remains controversial in patients with STEMI undergoing primary PCI,” according to background information in the article. “Early generation drug-eluting stents releasing sirolimus or paclitaxel from durable polymers reduce the need for repeat revascularization compared with bare-metal stents. However, vessel healing is delayed with evidence of chronic inflammation related at least in part to the persistence of durable polymer components in patients with acute STEMI. … Newer-generation drug-eluting stents with biodegradable polymers provide controlled drug release with subsequent degradation of the polymer rendering the stent surface more closely to a bare-metal stent after the period of biodegradation.”

Lorenz Räber, M.D., of Bern University Hospital, Bern, Switzerland, and colleagues compared the efficacy and safety of stents eluting biolimus from a biodegradable polymer with bare-metal stents of otherwise identical design. The randomized controlled trial included 1,161 patients with STEMI at 11 sites in Europe and Israel between September 2009 and January 2011. Clinical follow-up was performed at 1 and 12 months. Patients were randomized to receive the biolimus-eluting stent (n = 575) or the bare-metal stent (n = 582). The primary outcome measured for the study was the rate of major adverse cardiac events, a composite of cardiac death, target vessel-related reinfarction, and ischemia-driven target-lesion revascularization at 1 year. The average age of patients was 61 years and 79 percent were men.

The researchers found that at one year, the primary end point of major adverse cardiac events occurred in 4.3 percent of patients receiving biolimus-eluting stents and 8.7 percent of patients receiving bare-metal stents, which is a significant 4.4 percent absolute reduction and 51 percent relative reduction in the risk of major adverse cardiac events (and the prevention of 42 events per 1,000 patients treated with biolimus-eluting stents compared with bare-metal stents at 1 year). “For cardiac death alone, the percentages were smaller [(2.9 percent vs. 3.5 percent, respectively]. The treatment effect in favor of patients receiving biolimus-eluting stents was attributable to both a lower risk of target vessel-related reinfarction (0.5 percent vs. 2.7 percent) and ischemia-driven target-lesion revascularization (1.6 percent vs. 5.7 percent).”  At 1 year, rates of definite stent thrombosis amounted to 0.9 percent among patients receiving biolimus-eluting stents and 2.1 percent among patients receiving bare-metal stents.

The authors also observed no differences in all-cause and cardiac mortality between the groups at 1 year. “In addition to the device-oriented primary outcome measure, we recorded a lower risk of the comprehensive patient-oriented composite of death, any reinfarction, and any revascularization in favor of biolimus-eluting stents (8.4 percent vs. 12.2 percent).”

“… our results suggest better clinical outcomes in terms of major adverse cardiac events of a stent releasing biolimus from a biodegradable polymer compared with a bare-metal stent for the treatment of patients with STEMI.”

(JAMA. 2012;308[8]:777-787. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, August 21 at this link.

Editorial: New-Generation Drug-Eluting Stents for Patients With Myocardial Infarction

In an accompanying editorial, Salvatore Cassese, M.D., and Adnan Kastrati, M.D., of the Technische Universitat, Munich, Germany, write that the findings from this study (COMFORTABLE AMI) and from a series of previous trials on drug-eluting stents (DESs) in patients with heart attack provide several important lessons.

“First, the efficacy of DESs vs. bare-metal stents (BMSs) in STEMI is already established and, therefore, further studies comparing these interventions might not be needed. Second, concerns about a possible very late safety issue with DESs are apparently DES-type specific, mostly related to first-generation DESs and less justified with newer DESs. Larger randomized trials with longer follow-up and head-to-head comparisons of the available DES technologies are, however, required to completely eliminate these concerns. These studies should also take broader advantage of intravascular imaging technologies to provide mechanistic insights into the clinical findings. Third, although there is almost no rationale for performing DES vs. BMS studies anymore, it might be conceivable to expect studies that test the hypothesis of noninferiority of new, improved BMSs to available DESs. Until then, recent studies such as the COMFORTABLE AMI trial should make cardiologists feel more comfortable with the use of new-generation DESs in patients with STEMI.”

(JAMA. 2012;308[6]:619-620. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This work was supported by the European Commission. Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Kastrati holds a patent related to polymer-free sirolimus and probucol coating and reported receiving honoraria from Abbott, Biosensors, Cordis, and Medtronic. Dr. Cassese reports no conflicts.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 21, 2012

Media Advisory: To contact Joseph Yeboah, M.D., M.S., call Marguerite Beck at 336-716-2415 or email marbeck@wakehealth.edu. To contact editorial co-author J. Michael Gaziano, M.D., M.P.H., call Lori Schroth at 617-534-1604 or email ljschroth@partners.org.

CHICAGO – In a comparison of novel cardiovascular risk markers, coronary artery calcium, ankle-brachial index, high-sensitivity C-reactive protein, and family history were independent predictors of coronary heart disease/cardiovascular disease in intermediate-risk individuals beyond traditional risk factors, with coronary artery calcium providing superior discrimination and risk reclassification compared with other risk markers, according to a study in the August 22/29 issue of JAMA.

“Current trends in primary prevention of cardiovascular disease (CVD) emphasize the need to treat individuals based on their global cardiovascular risk. Accordingly, practice guidelines recommend approaches to classify individuals as high, intermediate, or low risk using the Framingham Risk Score (FRS) or other similar CVD risk prediction models. However, there is increasing recognition of the imprecision of these classifications such that the intermediate-risk group actually represents a composite of higher-risk individuals for whom more aggressive (i.e., drug) therapy might be indicated. The intermediate-risk group also contains lower-risk individuals in whom CVD might be managed with lifestyle measures alone. This recognition has motivated researchers to identify markers that could offer greater discrimination of higher- and lower-risk patients within the intermediate-risk group,” according to background information in the article.

“Risk markers including coronary artery calcium (CAC), carotid intima-media thickness (CIMT), ankle-brachial index (ABI), brachial flow-mediated dilation (FMD), high-sensitivity C-reactive protein (CRP), and family history of coronary heart disease (CHD) have been reported to improve on the Framingham Risk Score for prediction of CHD, but there are no direct comparisons of these markers for risk prediction in a single cohort,” the authors write.

Joseph Yeboah, M.D., M.S., of the Wake Forest University School of Medicine, Winston-Salem, N.C., and colleagues assessed the improvements in CHD/CVD prediction accuracy and reclassification to high- and low-risk categories using CIMT, CAC, FMD, ABI, high-sensitivity CRP, and family history of CHD in asymptomatic adults classified as intermediate risk who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). Of 6,814 MESA participants from 6 U.S. field centers, 1,330 were intermediate risk, without diabetes mellitus, and had complete data on all 6 markers. Recruitment spanned July 2000 to September 2002, with follow-up through May 2011. Analysis was conducted to compare incremental contributions of each marker when added to the FRS, plus race/ethnicity. Incident CHD was defined as heart attack, angina followed by revascularization, resuscitated cardiac arrest, or CHD death. Incident CVD additionally included stroke or CVD death.

After a median (midpoint) follow-up of 7.6 years, 94 participants (7.1 percent) experienced a CHD event and 123 (9.2 percent) experienced a CVD event. After analyses, the researchers found that each of the novel risk markers was associated with incident CHD; however, after adjusting for confounders, the associations with CIMT and FMD were no longer significant. Among all of the risk markers, CAC had the strongest association. Similarly, for incident CVD, each of the markers was associated with events except high-sensitivity CRP. However, after adjusting for confounders, the associations between CIMT and FMD were no longer significant. CAC also had the strongest association in the multivariable models for CVD.

“The current study shows that among 6 of the most promising novel risk markers, CAC provides the highest improvement in discrimination over the FRS and Reynolds score (RS) in individuals classified as intermediate risk. The present study provides additional support for the use of CAC as a tool for refining cardiovascular risk prediction in individuals classified as intermediate risk by the FRS or the RS,” the authors write. “Additional research is warranted to explore further both the costs and benefits of CAC screening in intermediate-risk individuals.”

(JAMA. 2012;308[8]:788-795. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Cardiovascular Risk Assessment in the 21st Century

In an accompanying editorial, J. Michael Gaziano, M.D., M.P.H., of the Boston VA Healthcare System, Brigham and Women’s Hospital, Harvard Medical School, Boston, (and Contributing Editor, JAMA), and Peter W. F. Wilson, M.D., of the Atlanta VA Medical Center and Emory Clinical Cardiovascular Research Institute, comment on the two studies in this issue of JAMA on assessing cardiovascular risk.

“These reports illustrate the means by which the enhancement of a given model such as FRS with additional data is evaluated. Area under the receiver operating characteristic curve has been used for many diagnostic tests. A clinically useful approach describes the proportion of individuals who are reclassified, known as the net reclassification index. However, not all reclassifications are created equally. Refining risk estimation at the low or high end of the risk spectrum is not helpful because it will not likely alter management. On the other hand, reclassification can assist in decision making for patients who are near clinical decision boundaries. For this reason, both studies provided information on the reclassification that occurred among those at 5 percent to 20 percent risk. In this intermediate range, risk estimates inform clinical decisions about certain interventions.”

(JAMA. 2012;308[8]:816-817. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 14, 2012

Media Advisory: To contact the corresponding author for the first study, Takeshi Tanigawa, M.D., Ph.D., email tt9178tt9178@gmail.com. To contact the corresponding author for the second study, Masaharu Tsubokura, M.D., email tsubokura-tky@umin.ac.jp.

CHICAGO – The results of two studies in the August 15 issue of JAMA report on the psychological status of workers at the Fukushima nuclear power plants in Japan several months after the earthquake and tsunami in March 2011, and the amount of internal radiation exposure among residents of a city north of the power plant that experienced a meltdown.

As reported in a Research Letter, Jun Shigemura, M.D., Ph.D., of the National Defense Medical College, Saitama, Japan, and colleagues examined the psychological status of Fukushima workers 2 to 3 months after the disaster for symptoms of general psychological distress, including posttraumatic stress response (PTSR). The study included all full-time workers from the Daiichi plant (n = 1,053; plant experienced meltdown) and Daini plant (n = 707; plant experienced damage but remained intact) in May and June 2011. Using a self-report questionnaire, the researchers assessed sociodemographic characteristics and disaster-related experiences, including discrimination/slurs because the electric company that managed these plants was criticized for their disaster response and the workers have been targets of discrimination. Measures of general psychological distress included feeling nervous, hopeless, restless/fidgety, depressed, and worthless in the last 30 days.

Of 1,760 eligible workers, 1,495 (85 percent) participated (Daiichi: n = 885 [84 percent]; Daini: n = 610 [86 percent]). The authors found that compared with Daini workers, Daiichi workers were more often exposed to disaster-related stressors. Experiencing discrimination or slurs was not statistically significantly different between groups (14 percent vs. 11 percent). The researchers found that general psychological distress and PTSR were common in nuclear plant workers 2 to 3 months after the disaster. “Daiichi workers had significantly higher rates of psychological distress (47 percent vs. 37 percent) and PTSR (30 percent vs. 19 percent). For both groups, discrimination or slurs were associated with high psychological distress and high PTSR. Other significant associations in both groups included tsunami evacuation and major property loss with psychological distress and pre-existing illness and major prop­erty loss with PTSR.”

(JAMA. 2012;308[7]:667-669. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This work was supported by Health and Labour Sciences Research Grants from the Ministry of Health Labour and Welfare of Japan. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Study Finds Low Levels of Radiation Exposure to Residents of City North of Meltdown

In another Research Letter, Masaharu Tsubokura, M.D., of the University of Tokyo, and colleagues conducted a study to gauge the level of radiation exposure to residents of the city of Minamisoma, located 14 miles north of the Fukushima Daiichi nuclear plant. “Release of radioactive material into the air, water, and soil raised concern about internal radiation exposure and the long-term risk of cancer in nearby residents,” they write.

Many residents were evacuated after the meltdown, but by August 2011, approximately half had returned. A voluntary screening program for levels of cesium, known to be representative of total internal radiation exposure, was conducted between September 2011 and March 2012 for all residents ages 6 years or older. Total cesium exposure was converted into committed effective dose (sievert, Sv). Common dose-limit recommendations for the public are 1 mSv or less. A total of 9,498 residents enrolled in the study, 24 percent of the registered population on August 15, 2011. The sample consisted of 1,432 children and 8,066 adults. A total of 3,286 individuals (34.6 percent) had detectable levels of cesium, including 235 children (16.4 percent) and 3,051 adults (37.8 percent). Committed effective doses were less than 1 mSv in all but 1 resident (1.07 mSv).

“To our knowledge, this is the first report on internal exposure to cesium radiation after the Fukushima Daiichi nuclear plant incident. In this sample, exposure levels were low in most adults and children tested and much lower than those reported in studies years after the Chernobyl incident. Even the highest levels of contamination observed are below the thresholds for the administration of Prussian blue [an antidote used in the treatment of cesium poisoning],” the authors write.

The researchers note that because this screening program started 6 months after the nuclear power plant disaster, higher exposure levels might have been detected earlier, and that it is not possible to ascertain whether the low levels of exposure were due to low ongoing exposure or decay from high exposure values. “Because data were collected from volunteers, the results may not be representative of the entire population in contaminated areas. No case of acute health problems has been reported so far; however, assessments of the long-term effect of radiation requires ongoing monitoring of exposure and the health conditions of the affected communities.”

(JAMA. 2012;308[7]:669-670. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 14, 2012

Preventing Suicides in U.S. Service Members and Veterans – Concerns After a Decade of War

Charles W. Hoge, M.D., of the Walter Reed Army Institute of Research, Silver Spring, Md., and Carl A. Castro, Ph.D., of the U.S. Army Medical Research and Materiel Command, Fort Detrick, Md., write that “between 2005 and 2009, the incidence of suicide in Army and Marine personnel nearly doubled. From 2009 through the first half of 2012, the incidence of suicide among Army soldiers remained elevated (22 per 100,000 per year), with the number dying of suicide each year exceeding the number killed in action.” In this Viewpoint, the authors discuss issues such as screening and risk assessment, education and public awareness, and treatment.

“The most important challenges in suicide prevention are stigma surrounding mental illness, negative perceptions of treatment, and other barriers (including confidentiality concerns in the military setting) that result in the majority of service members and veterans not accessing care when needed or dropping out prematurely. It is imperative that intervention strategies—and research efforts—prioritize patient engagement and satisfaction, screening for underlying mental disorders in primary care, care coordination, capacity for timely appointments, effective treatment, and reinforcing protective effects of family and peer connections.”

(JAMA. 2012;308[7]:671-672. Available pre-embargo to the media at http://media.jamanetwork.com)

The State of the World’s Refugees – Adapting Health Responses to Urban Environments

Antonio Guterres, M.Eng., United Nations High Commissioner for Refugees, Geneva, Switzerland, and Paul Spiegel, M.D., M.P.H., of the Office of the United Nations High Commissioner for Refugees, write that the “forced displacement of populations, across borders and within their own countries, is one of the most visible and enduring manifestations of persecution and conflict. At the end of 2011, more than 42 million people had been forcibly displaced from their homes by conflict, including 15 million refugees and 26 million internally displaced people.”  They note that a phenomenon of urbanization is affecting refugees and displaced people, with 58 percent of adult refugees living in cities. The authors discuss the challenges and consequences of this urbanization issue, and address health needs and initiatives that have been beneficial.

“Innovations in access to care will have a meaningful effect only if they form part of a comprehensive protection-based approach addressing the needs of refugees and internally displaced people across a range of sectors, including livelihoods, education, nutrition, water and sanitation, and the environment. Only by addressing these in an integrated manner, within a framework that promotes self-reliance and durable solutions, will reductions in morbidity and mortality be achieved, along with a real improvement in the quality of life for the world’s 40 million refugees and displaced persons—until they can return home.”

(JAMA. 2012;308[7]:673-674. Available pre-embargo to the media at http://media.jamanetwork.com)

A Framework for Catastrophic Disaster Response

Dan Hanfling, M.D., of the Inova Health System, Falls Church, Va., and colleagues write that the Japanese tsunami, Haitian earthquake, and Gulf Coast hurricane offered stark reminders of how vulnerable organized societies are to catastrophic events. In this Viewpoint, the authors examine 3 critical components of catastrophic disaster preparedness: the development of crisis standards of care; development of a “systems” approach that ensures integration among key stakeholders; and meaningful engagement with health professionals and the public.

“To reduce morbidity and death, and to ensure democratic accountability, the government and health system at every level will need to plan carefully, adopt ethically rigorous standards, and meaningfully engage professionals. What is most important is that government and stakeholders—from local communities to states and nationally—design and test a rigorous response well in advance of a major disaster.”

(JAMA. 2012;308[7]:675-676. Available pre-embargo to the media at http://media.jamanetwork.com)

Sexual Violence as a Weapon of War

Lindsay Stark, Dr.P.H., and Mike Wessells, Ph.D., of the Mailman School of Public Health, Columbia University, New York, write that there is an increased understanding that rape is used as a strategic and systematic tactic during armed conflict. In this Viewpoint, the authors examine why sexual violence is an effective weapon of war, its health and psychosocial sequelae, and its association with other forms of gender-based violence.

“To aid prevention and support survivors, additional research is needed to address important questions. For example, in different conflict settings, what proportion of sexual violence is perpetrated by soldiers and armed groups as opposed to partners, spouses, and other family members? To what extent do these forms of sexual violence have common or interrelated causes? How can steps toward prevention build on what is known about changing norms of abuse, discrimination, and devaluation of women in nonconflict settings? Which interventions—individual and communal— are most effective in supporting survivors? Particularly needed are assessments of different approaches to reducing the severe stigma and isolation that typically follow wartime sexual violence and for enhancing survivors’ coping skills. Answering these and related questions requires acknowledging sexual violence as a weapon of war and as a critical component of the public health research agenda in conflict-affected settings.”

(JAMA. 2012;308[7]:677-678. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 14, 2012

Media Advisory: To contact Katherine L. Mills, Ph.D., email k.mills@unsw.edu.au.

CHICAGO – Study participants who received an integrated treatment for posttraumatic stress disorder (PTSD) and substance dependence plus usual treatment for substance dependence showed significantly greater reductions in PTSD symptom severity compared with participants who only received usual treatment for substance dependence, according to a study in the August 15 issue of JAMA, a theme issue on violence and human rights.

“Prolonged exposure therapy, a cognitive-behavioral therapy involving exposure to memories and reminders of past trauma, has long been regarded as a gold standard treatment for PTSD,” according to background information in the article.  There is a concern, however, that exposure therapy may be inappropriate because of risk of relapse for patients with co-occurring substance dependence. “There is, however, an absence of evidence to support or refute this recommendation, because most trials of PTSD treatment have excluded individuals with substance dependence.”

Katherine L. Mills, Ph.D., of the University of New South Wales, Sydney, Australia, and colleagues conducted what is believed to be the first randomized controlled trial of an integrated treatment for PTSD and substance dependence that incorporates prolonged exposure therapy. The study enrolled 103 participants who met criteria for both PTSD and substance dependence. Participants were recruited from 2007-2009; outcomes were assessed at 9 months, with interim measures collected at 6 weeks and 3 months.  Participants were randomized to receive either an integrated treatment for PTSD and substance dependence called Concurrent Treatment of PTSD and Substance Use Disorders Using Prolonged Exposure (COPE), plus usual treatment for substance dependence (n = 55); or usual treatment alone (control) (n = 48). COPE consists of 13 individual 90-minute sessions (i.e., 19.5 hours) with a clinical psychologist.

The primary outcomes measured were changes in severity of PTSD symptoms and substance dependence.

The researchers found that from the beginning of the study to 9-month follow-up, significant reductions in PTSD symptom severity were found for both the treatment group and the control group; however, the treatment group demonstrated a significantly greater reduction in PTSD symptom severity compared with the control group.

By the 9-month follow-up, rates of substance dependence had decreased to 45.4 percent in the treatment group and 56.2 percent in the control group; however, the difference between groups was not statistically significant. Both the treatment and the control group also demonstrated significant reductions in severity of dependence from baseline to 9-month follow-up; however, the degree of change did not differ significantly between groups. Also, there were not any significant between-group differences in relation to changes in substance use, depression, or anxiety.

The researchers write that it is important to note that most participants randomized to receive COPE plus usual treatment continued to use substances throughout the study. “These findings challenge the widely held view that patients need to be abstinent before any trauma work, let alone prolonged exposure therapy, is commenced. Although we agree that patients need to show some improvement in their substance use and an ability to use alternative coping strategies before prolonged exposure therapy is initiated, findings from the present study demonstrate that abstinence is not required.”

(JAMA. 2012;308[7]:690-699. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This study was funded by a Australian National Health and Medical Research Council project grant. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 14, 2012

Media Advisory: To contact Joanne Klevens, M.D., Ph.D., call Gail Hayes at 770-488-4902 or email shayes@cdc.gov. To contact editorial co-author C. Nadine Wathen, Ph.D., call Jeff Renaud at 519-661-2111, ext. 85165, or email jrenaud9@uwo.ca.

CHICAGO – In a study that included more than 2,700 women receiving care in primary care clinics, those who were screened for partner violence and received a partner violence resource list did not experience significant differences for several outcomes, including overall quality of life, general health, and recurrence of partner violence, compared to women who just received a partner violence resource list, according to a study in the August 15 issue of JAMA, a theme issue on violence and human rights.

“Recognition of partner violence as a health and public health problem has led numerous professional and health care organizations, as well as the Institute of Medicine, to recommend screening (i.e., testing asymptomatic patients to identify those requiring special intervention) or assessment of women for partner violence in primary care settings. However, the United States Preventive Services Task Force, the Canadian Task Force, and the United Kingdom’s Health Technology Assessment Program have concluded there is insufficient evidence to support this recommendation,” according to background information in the article.

Joanne Klevens, M.D., Ph.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues from Chicago area hospitals conducted a study to evaluate the effect of computer-based partner violence screening and distribution of local partner violence resource lists to women seeking care in outpatient clinical settings. The study was a 3-group randomized controlled trial at 10 primary health care centers in Cook County, Illinois. Participants were enrolled from May 2009 – April 2010, and included 2,364 women who were re-contacted 1 year after enrollment. The women were predominantly non-Latina African American (55 percent) or Latina (37 percent), had a high school education or less (57 percent), and were uninsured (57 percent).

The participants were randomized into 3 intervention groups: (1) partner violence screen (using the Partner Violence Screen instrument) plus a list of local partner violence resources if screening was positive (n = 909); (2) partner violence resource list only without screen (n = 893); and (3) no-screen, no-partner violence list control group (n = 898). For the Partner Violence Screen instrument, trained research assistants approached potential participants in each clinic’s waiting room to determine their interest and eligibility. Participants completed an audio-computer-assisted self-interview, which consisted of several questions regarding partner violence, in private rooms or kiosks equipped with touch-screen computers and headphones. Women who screened positive (affirmative response to 1 or more questions) were shown a brief video on the computer screen in which a partner violence advocate provided support and information about the hospital-based partner violence advocacy program and encouraged the viewer to seek help. Women who screened negative received the list of general resources only.

The primary outcomes measured for the study were quality of life (QOL, physical and mental health components, measured on the 12-item Short Form [scale range 0-100, average score of 50 for U.S. population]). Days lost from work or household activities, use of health care and partner violence services, and the recurrence of partner violence were secondary outcomes.

The researchers found that at 1-year follow-up, average scores on the QOL components and subscales ranged from 44 to 52 among all women with no statistically significant differences by study group status for any of the components or subscales. There were also no differences between groups in days unable to work or complete housework; number of hospitalizations, emergency department, or ambulatory care visits; or proportion who contacted a partner violence agency.

At follow-up, 9.9 percent of women (235/2,362) reported experiencing partner violence in the year before enrolling in the study and in the previous year (recurrence), with no statistically significant difference between study groups.

“In conclusion, the results of this study suggest providing a partner violence resource list with or without computerized screening of female adult patients in primary care settings does not result in significant benefits in terms of general health outcomes. These findings provide important information for clinicians and others to consider in light of recent professional recommendations calling for routine screening,” the authors write.

(JAMA. 2012;308[7]:681-689. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This study was supported by the Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, Division of Violence Prevention. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Sadowski reports receipt of consultancy fees from the World Health Organization. The other authors report no disclosures.

Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, August 14 at this link.

Editorial: Health Care’s Response to Women Exposed to Partner Violence – Moving Beyond Universal Screening

In an accompanying editorial, C. Nadine Wathen, Ph.D., of Western University, London, Ontario, and Harriet L. MacMillan, M.D., M.Sc., F.R.C.P.C., of McMaster University, Hamilton, Ontario, write that this and another large-scale trial have shown that universal screening does not improve women’s health or life quality or reduce re-exposure to partner violence.

“It is time to enact an approach in which individual women are assessed according to their presenting histories, which include symptoms and risks. With exposure to partner violence being understood in the context of its health-relevant consequences, clinical teams may more effectively be able to address these issues. Although there may be emerging evidence regarding specific counseling and advocacy programs in reducing partner violence and improving health outcomes for women, replication in larger and more diverse samples using rigorous methods is required. Another important goal of research and policy, along with evaluation of primary prevention interventions, is to develop coordinated care models that will allow seamless referral and transition of women from the clinic to appropriate community-based services.”

(JAMA. 2012;308[7]:712-713. Available pre-embargo to the media at http://media.jamanetwork.com)

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 14, 2012

Media Advisory: To contact Candice M. Monson, Ph.D., call Suelan Toye at 416-979-5000, ext. 7161 or email stoye@ryerson.ca. To contact editorial author Lisa M. Najavits, Ph.D., call Gina DiGravio at 617-638-8480 or email gina.digravio@bmc.org.

CHICAGO – Among couples in which one partner was diagnosed as having posttraumatic stress disorder (PTSD), participation in disorder-specific couple therapy resulted in decreased PTSD symptom severity and increased patient relationship satisfaction, compared with couples who were placed on a wait list for the therapy, according to a study in the August 15 issue of JAMA, a theme issue on violence and human rights.

“There are well-documented associations between PTSD and intimate relationship problems, including relationship distress and aggression, and studies demonstrate that the presence of PTSD symptoms in one partner is associated with caregiver burden and psychological distress in the other partner. Although currently available individual psychotherapies for PTSD produce overall improvements in psychosocial functioning, these improvements are not specifically found in intimate relationship functioning. Moreover, it has been shown that even when patients receive state-of-the-art individual psychotherapy for the disorder, negative interpersonal relations predict worse treatment outcomes,” according to background information in the article.

Candice M. Monson, Ph.D., of Ryerson University, Toronto, Canada, and colleagues conducted a study to examine the effect of a cognitive-behavioral conjoint therapy (CBCT) for PTSD, designed to treat PTSD and its symptoms and enhance intimate relationships in couples. The randomized controlled trial, conducted from 2008 to 2012, included heterosexual and same-sex couples (n = 40 couples; n = 80 individuals) in which one partner met criteria for PTSD according to the Clinician-Administered PTSD Scale. Symptoms of PTSD, co-existing conditions, and relationship satisfaction were collected by assessors at the beginning of the study, at mid treatment (median [midpoint], 8 weeks after baseline), and at post-treatment (median, 16 weeks after baseline). An uncontrolled 3-month follow-up was also completed. Couples were randomly assigned to take part in the 15-session cognitive-behavioral conjoint therapy for PTSD protocol immediately (n = 20) or were placed on a wait list for the therapy (n = 20). Clinician-rated PTSD symptom severity was the primary outcome; intimate relationship satisfaction, patient- and partner-rated PTSD symptoms, and co-existing symptoms were secondary outcomes.

The researchers found that PTSD symptom severity and patients’ intimate relationship satisfaction were significantly more improved in couple therapy than in the wait-list condition. Also, change ratios (calculated by dividing the change in the CBCT condition from pretreatment to post-treatment by the change in the wait-list condition over this period) indicated that PTSD symptom severity decreased almost 3 times more in CBCT from pretreatment to post-treatment compared with the wait list; and patient-reported relationship satisfaction increased more than 4 times more in CBCT compared with the wait list.

The secondary outcomes of depression, general anxiety, and anger expression symptoms also improved more in CBCT relative to the wait list.

Treatment effects were maintained at 3-month follow-up.

“This randomized controlled trial provides evidence for the efficacy of a couple therapy for the treatment of PTSD and comorbid symptoms, as well as enhancements in intimate relationship satisfaction. These improvements occurred in a sample of couples in which the patients varied with regard to sex, type of trauma experienced, and sexual orientation. The treatment effect size estimates found for PTSD and comorbid symptoms were comparable with or better than effects found for individual psychotherapies for PTSD. In addition, patients reported enhancements in relationship satisfaction consistent with or better than prior trials of couple therapy with distressed couples and stronger than those found for interventions designed to enhance relationship functioning in nondistressed couples,” the authors write.

“Cognitive-behavioral conjoint therapy may be used to efficiently address individual and relational dimensions of traumatization and might be indicated for individuals with PTSD who have stable relationships and partners willing to engage in treatment with them.”

(JAMA. 2012;308[7]:700-709. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This study was supported by a National Institute of Mental Health grant to Dr. Monson. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Expanding the Boundaries of PTSD Treatment

Lisa M. Najavits, Ph.D., of the Veterans Affairs Boston Healthcare System and Boston University School of Medicine, comments in an accompanying editorial on the 2 studies in this issue of JAMA on treating PTSD.

“The results of the trials by Mills at al and Monson et al are important scientific attempts to study new options for treatment of PTSD. Overall, comparative studies of PTSD therapies find that they rarely outperform each other in efficacy. Thus, the cost and appeal of treatments to clinicians and patients, their intensity of intervention, and clinical setting and training issues may ultimately be as or more relevant than comparative efficacy in choosing a course of treatment for PTSD. In the current era, there is a focus on short-term treatments (in part an antidote to the overly long psychotherapies of much of the 20th century). However, it is not clear how long treatment needs to be maintained to produce enduring positive outcomes, especially for patients with PTSD and comorbidities and difficult social circumstances. The field of PTSD therapy is still young, and the pursuit of clinically meaningful treatments for all types of patients, like the process of recovery for patients with PTSD, is an ongoing challenge.”

(JAMA. 2012;308[7]:714-716. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of interest and reported receiving royalties from Guilford Press and New Harbinger Press and that she is director of Treatment Innovations, which provides consultation, training, and materials related to psychotherapy.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 7, 2012

Transcatheter Valve Replacement for Aortic Stenosis – Balancing Benefits, Risks, and Expectations

Chintan S. Desai, M.D., and Robert O. Bonow, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, write that “transcatheter aortic valve replacement (TAVR) represents a transformative technology with potential for the management of complex patients with aortic stenosis, including those who are not considered candidates for surgical aortic valve replacement because of age and medical comorbidities. Currently, more than 50,000 TAVR procedures have been performed worldwide, with mounting enthusiasm for the ‘rational dispersion’ of transcatheter therapies.”

The authors note that “the increasing consumer expectations that this therapy might become available soon for even young, low-risk patients requiring valve replacement must be balanced against safety concerns that have arisen in both clinical trials and registries.”

(JAMA. 2012;308[6]:573-574. Available pre-embargo to the media at http://media.jamanetwork.com)

The Importance of Potential Studies That Have Not Existed and Registration of Observational Data Sets

John P. A. Ioannidis, M.D., D.Sc., of the Stanford University School of Medicine, Stanford, Calif., examines the issue of potential studies that do not exist, studies that could readily have been conducted. “Is it possible to know the unknowable? It is important to consider why studies have not been conducted and what could be done about them. Related to this phenomenon is the continuing problem of unregistered, exploratory observational studies often derived from large data sets.”

“When the number of potential studies that have not existed is large, then the published literature is mostly a reflection of what is considered plausible and reasonable by experts in the field. Thousands of scientists could have data-peeked; their decision to generate and publish a full study with specific results is molded by their expectations and the expectations of peers. Although researchers often come across unexpected, implausible findings, data shaped into publishable studies are mostly those that seem orthodox to peers— plus some extravagant studies in which investigators venture bold claims. When only 1 percent of the potential studies see the light of day, this 1 percent is often a conformity sample, not a random one.”

(JAMA. 2012;308[6]:575-576. Available pre-embargo to the media at http://media.jamanetwork.com)

Payment Reform for Primary Care Within the Accountable Care Organization – A Critical Issue for Health System Reform

Allan H. Goroll, M.D., of Harvard Medical School and Massachusetts General Hospital, Boston, and Stephen C. Schoenbaum, M.D., M.P.H., of the Josiah Macy Jr. Foundation, New York, write that “primary care, the foundation of the accountable care organizations (ACOs), requires payment reform to enable and make durable its transformation into a high-performance model such as the patient-centered medical home.”

The authors examine the major barriers to primary care payment reform and the measures needed to address these impediments.

“Payment reforms must overcome the suspicions and distrust of change that have built up over the last 2 decades within much of the physician community. There must be, and physicians must have confidence in, a commitment by new organizations such as ACOs to provide practices with the supports necessary for them to do their jobs well and to pay commensurately with the value they create. Such payment reform can provide the basis for a new social contract between the profession and society and help achieve the goal needed by the nation of better health care at lower cost.”

(JAMA. 2012;308[6]:577-578. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 7, 2012

Media Advisory: To contact Mercedes R. Carnethon, Ph.D., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu. To contact Hermes Florez, M.D., M.P.H., Ph.D., call Lisa Worley at 305-243-5184 or email lworley2@med.miami.edu.

CHICAGO – Participants in a study who were normal weight at the time of a diagnosis of diabetes experienced higher rates of total and noncardiovascular death compared with those who were overweight or obese at diabetes diagnosis, according to a study in the August 8 issue of JAMA.

“Type 2 diabetes in normal-weight adults is an understudied representation of the metabolically obese normal-weight phenotype that has become increasingly common over time. It is not known whether the ‘obesity paradox’ that has been observed in chronic diseases such as heart failure, chronic kidney disease, and hypertension extends to adults who are normal weight at the time of incident diabetes,” according to background information in the article

Mercedes R. Carnethon, Ph.D., of the Feinberg School of Medicine, Northwestern University, Chicago, and colleagues conducted a study to compare mortality between participants who were normal weight and overweight/obese at the time of new adult-onset diabetes. The study consisted of a pooled analysis of 5 longitudinal studies with a total of 2,625 participants with new diabetes. Included were men and women (older than 40 years of age) who developed incident diabetes based on fasting glucose 126 mg/dL or greater or newly initiated diabetes medication and who had concurrent measurements of body mass index (BMI). Participants were classified as normal weight if their BMI was 18.5 to 24.99 or overweight/obese if BMI was 25 or greater. Half (50 percent) of the participants were women, 36 percent were non-white.

The proportion of adults who were normal weight at the time of incident diabetes ranged from 9 percent to 21 percent (overall 12 percent). During follow-up, 449 participants died: 178 (6.8 percent) from cardiovascular causes and 253 (10.4 percent) from noncardiovascular causes; 18 causes of death were unidentified. In the pooled sample, total mortality and cardiovascular and noncardiovascular mortality were higher in normal-weight participants as compared with rates among overweight or obese participants. Following adjustment for certain variables, the researchers found that participants with normal-weight diabetes experienced a significantly elevated total mortality and noncardiovascular mortality. While cardiovascular mortality was elevated, the association was not statistically significant.

“These findings are relevant to segments of the U.S. population, including older adults and nonwhite persons (e.g., Asian, black), who are more likely to experience normal-weight diabetes.”

The researchers write that mechanisms to explain their findings are unknown. “However, previous research suggests that normal-weight persons with diabetes have a different genetic profile than overweight or obese persons with diabetes. If those same genetic variants that predispose to diabetes are associated with other illnesses, these individuals may be ‘genetically loaded’ toward experiencing higher mortality. Future research in normal-weight persons with diabetes should test these genetic hypotheses, along with other plausible mechanisms to account for higher mortality, including inflammation, the distribution and action of adipose tissue, atherosclerosis burden and the composition of fatty plaques, and pancreatic beta-cell function.”

(JAMA. 2012;308[6]:581-590. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This research is funded by a National Institute of Diabetes and Digestive and Kidney Disease grant. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Beyond the Obesity Paradox in Diabetes – Fitness, Fatness, and Mortality

In an accompanying editorial, Hermes Florez, M.D., M.P.H., Ph.D., and Sumaya Castillo-Florez, M.D., M.P.H., of the University of Miami Miller School of Medicine, and Miami Veterans Affairs Healthcare System, write that “the article by Carnethon et al addresses an emerging challenge regarding diabetes and weight status.”

“This could be a wake-up call for timely prevention and management to reduce adverse outcomes in all patients with type 2 diabetes, particularly in those metabolically obese normal-weight at diagnosis, who may have a false sense of protection because they are not overweight or obese. Standards of diabetes care recommend weight loss for all overweight or obese individuals who have diabetes. Low carbohydrate, low-fat, calorie-restricted, or Mediterranean diets may be effective weight-loss strategies in these individuals. The additional benefits of increased physical activity and behavior modification strategies may lead to the successful implementation of weight management and healthy living programs for all patients with diabetes. It is important to understand how diabetes duration relates to the benefits of intentional weight loss, as well as the clinical consequence associated with sarcopenic obesity and bone loss in older adults with or at high risk for diabetes.”

(JAMA. 2012;308[6]:619-620. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Support was provided by the Department of Veterans Affairs Geriatrics Research, Education, and Clinical Center program and a grant from the National Institutes of Health and Department of Health and Human Services. Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 7, 2012

Media Advisory: To contact Brian K. Kit, M.D., M.P.H., call Karen Hunter at 404-639-3286 or email ksh7@cdc.gov. To contact editorial author Sarah D. de Ferranti, M.D., M.P.H., call Rob Graham at 617-919-3110 or email rob.graham@childrens.harvard.edu.

CHICAGO – In a study involving more than 16,000 U.S. children and adolescents, there has been a decrease in average total cholesterol levels over the past 2 decades, although almost 1 in 10 had elevated total cholesterol in 2007-2010, according to a study in the August 8 issue of JAMA.

“The process of atherosclerosis begins during childhood and is associated with adverse serum lipid concentrations including high concentrations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides, and low concentrations of high-density lipoprotein cholesterol (HDL-C). Serum lipid concentrations in childhood are associated with serum lipid concentrations in adulthood,” according to background information in the article. “For more than 20 years, primary prevention of coronary heart disease has included strategies intended to improve overall serum lipid concentrations among youths.”

Brian K. Kit, M.D., M.P.H., of the Centers for Disease Control and Prevention, Hyattsville, Md., and colleagues conducted a study to examine the trends in serum lipid concentrations among children and adolescents in the U.S. The study included data on 16,116 youths ages 6 to 19 years who participated in the nationally representative National Health and Nutrition Examination Survey (NHANES) during 3 time periods: 1988-1994,1999-2002, and 2007-2010. Among the measures analyzed for all the participants were average serum total cholesterol (TC), non-HDL-C, HDL-C; and among adolescents only (ages 12-19 years), LDL-C and geometric average triglyceride levels. Trends in adverse lipid concentrations were reported for TC levels of 200 mg/dL and greater, non-HDL-C levels of 145 mg/dL and greater, HDL-C levels of less than 40 mg/dL, LDL-C levels of 130 mg/dL and greater, and triglyceride levels of 130 mg/dL and greater.

The researchers found that among youths ages 6 to 19 years between 1988-1994 and 2007-2010, there was a decrease in average serum TC from 165 mg/dL to 160 mg/dL and an increase in average serum HDL-C from 50.5 mg/dL to 52.2 mg/dL. There was also a decrease in the average serum non-HDL-C levels during this time period. “Generally, the sex-, age-, and race/ethnicity-specific trends for TC, HDL-C, and non-HDL-C were similar in direction to the overall trends and consistent with a favorable trend, although for each group, the magnitude was not the same and the trend was not always significant,” the authors write.

Between 1988-1994 and 2007-2010, there was a decrease in prevalence among youths ages 6 to 19 years of elevated TC from 11.3 percent to 8.1 percent and non-HDL-C from 13.6 percent to 10 percent. Prevalence of low HDL-C was 17.3 percent in 1988-1994 and 14.8 percent in 2007-2010, a nonsignificant decrease.  Among adolescents, there was a decrease in prevalence of elevated LDL-C and triglycerides between 1988-1994 and 2007-2010 and a decrease in average serum LDL-C from 95 mg/dL to 90 mg/dL and geometric average serum triglycerides from 82 mg/dL to 73 mg/dL.

In 2007-2010, 22 percent of youths had either a low HDL-C level or high non-HDL-C, which was lower than the 27.2 percent in 1988-1994.

The authors also found that age- and race/ethnicity-adjusted TC was 4.3 mg/dL lower for males and 6.5 mg/dL lower for females in 2007-2010 than in 1988-1994. Males and females who were non-Hispanic black or Mexican American, and also females who were non-Hispanic white had a lower age-adjusted TC in 2007-2010 than in 1988-1994. Age- and race/ethnicity- adjusted HDL-C was higher for males and females in 2007-2010 than in 1988-1994.

“Between 1988-1994 and 2007-2010, a favorable trend in serum lipid concentrations was observed among youths in the United States but adverse lipid profiles continue to be observed among youths,” the researchers write. “For example, in 2007-2010, slightly more than 20 percent of children aged 9 to 11 years had either a low HDL-C or high non-HDL-C concentration, which, according to the most recent cardiovascular health guidelines for children and adolescents, indicates a need for additional clinical evaluation.”

“The recently released Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents provides recommendations for preventing the development of cardiovascular risk factors including optimizing nutrition and physical activity and reducing exposure to tobacco smoke. Specific screening approaches, including universal screening at select ages and management of adverse lipid concentrations, have also been detailed in these recent guidelines for youths. Future research from longitudinal studies or mortality-linked data, including NHANES, may include examining clinical outcomes for cardiovascular disease, including cardiovascular mortality, based on lipid concentrations present during childhood,” the authors conclude.

(JAMA. 2012;308[6]:591-600. Available pre-embargo to the media at http://media.jamanetwork.com)

 Editor’s Note: The laboratory analysis of the lipids described in this paper was funded by a National Heart, Lung, and Blood Institute, National Institutes of Health, Intra-agency Agreement. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

 Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, August 7 at this link.

 Editorial: Declining Cholesterol Levels in U.S. Youths – A Reason for Optimism

Sarah D. de Ferranti, M.D., M.P.H., of Harvard Medical School and Boston Children’s Hospital, Boston, comments on the findings of this study in an accompanying editorial.

“Further research is needed to investigate the hypothesized contributors to change in childhood and adolescent lipid levels. Better understanding is needed about dietary trends and physical activity during childhood, areas that were not explored in the study by Kit et al but could be assessed using NHANES data. However it seems clear that population-wide efforts to alter cardiovascular disease [CVD] risk have potential to influence health risks. Examples of other interventions that could have positive population-level effects on health include taxation of carbonated beverages, improved access to water in schools and in the workplace, and environmental changes to promote daily physical activity. Improvements in child and adolescent lipid values over the past 2 decades are significant and may portend improved CVD outcomes for the future, but much work should be done to better understand the changes and to build upon them.”

(JAMA. 2012;308[6]:621-622. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. de Ferranti reports receipt of grants or pending grants from the National Institutes of Health/National Heart, Lung, and Blood Institute; payment for lectures including service on speakers bureaus from the Pediatric Endocrine Society, the Pediatric Rheumatology Society, and Covidien; and receipt of royalties from UpToDate.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 31, 2012

Study Evaluates Association of Pertussis Vaccine Type and Administration With Reports of Pertussis Cases

Similar to North America, Australia is experiencing a sustained pertussis epidemic, with the highest incidence rates in Queensland during 2011 in children age 6 to 11 years. The recent changes in pertussis epidemiology may be related to a shift in vaccines from diphtheria-tetanus-whole cell pertussis (DTwP) to diphtheria-tetanus-acellular pertussis (DTaP) because of a lower rate of adverse events. Sarah L. Sheridan, B.Med., M.App.Epid., and colleagues with the University of Queensland, Brisbane, Australia, conducted a study to compare pertussis reporting rates by primary course vaccination in the 1998 birth cohort in Queensland.

As reported in a Research Letter, of 58,233 children born in 1998 identified in the Queensland vaccination register, 40,494 (69.5 percent) received at least 3 doses of any pertussis-containing vaccine during the first year from a Queensland vaccine service provider and were included in the analysis. Overall, 267 first pertussis cases were reported from this cohort between 1999 and 2011; 2 second reports were excluded. The researchers found that children who received a 3-dose DTaP primary course had higher rates of pertussis than those who received a 3-dose DTwP primary course in the pre-epidemic and outbreak periods. Among those who received mixed courses, rates in the current epidemic were highest for children receiving DTaP as their first dose.

(JAMA. 2012;308[5]:454-456. Available pre-embargo to the media at http://media.jamanetwork.com)

Viewpoints in This Week’s JAMA

Curbing the Opioid Epidemic in the United States – The Risk Evaluation and Mitigation Strategy

Lewis S. Nelson, M.D., of the New York University School of Medicine, and Jeanmarie Perrone, M.D., of the University of Pennsylvania, Philadelphia, discuss the use of a risk evaluation and mitigation strategy (REMS) to help deal with the problem of the “opioid epidemic” in the United States. REMS is a U.S. Food and Drug Administration-required strategy to manage a known or potential serious risk associated with a drug or biological product.

“Prescriber and patient education alone will likely prove insufficient to assuage the concerns of patients with chronic noncancer pain, who fear the reduced availability of opioid pain relievers, and public health advocates, who fear the excessive use of these drugs. Although at its core the opioid epidemic may be iatrogenic, additional regulation may be needed to help ensure more informed and appropriate prescribing. The REMS approach, if implemented appropriately and followed correctly, may be an important component for addressing the opioid epidemic in the United States.”

(JAMA. 2012;308[5]:457-458. Available pre-embargo to the media at http://media.jamanetwork.com)

Potential Consequences of Reforming Medicare Into a Competitive Bidding System

Zirui Song, Ph.D., of Harvard Medical School, Boston, and colleagues write that premium support (or vouchers), based on competitive bidding, may offer a fiscal solution if Affordable Care Act (ACA) reforms fail, but at the cost of making Medicare beneficiaries responsible for solving Medicare’s fiscal crisis.

“Success of the ACA can make premium support less risky by lowering traditional Medicare costs and helping to monitor and improve quality in private plans. Without ACA improvements, beneficiaries must pay more for traditional Medicare or join a private plan. Given the current fiscal pressures, this may be acceptable, but it is a major shift from traditional Medicare that may have deleterious consequences.”

(JAMA. 2012;308[5]:457-458. Available pre-embargo to the media at http://media.jamanetwork.com)

Integrating Public Health and Primary Care Systems – Potential Strategies From an IOM Report

Bruce E. Landon, M.D., M.B.A., of Harvard Medical School, Boston, and colleagues examine reasons there may be progress in integrating public health and primary care.

“The efforts of the primary care clinician and the public health official on behalf of the patients and communities they jointly serve must be increasingly coordinated, complementary, mutually accountable, well informed by data, and comprehensive. The policy, practice, and information environments are now conducive to achieving the elusive goal of a transformed, robust, and equitable population health system.”

(JAMA. 2012;308[5]:461-462. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 31, 2012

Media Advisory: To contact corresponding author Peter K. Smith, M.D., call Debbe Geiger at 919-660-9461 or email debbe.geiger@dm.duke.edu. To contact editorial author Lawrence J. Dacey, M.D., M.S., call David Corriveau at 603-653-1978 or email David.A.Corriveau@hitchcock.org.

CHICAGO – Although there have been questions regarding the safety and durability of endoscopic vein graft harvest for coronary artery bypass graft (CABG) surgery, an analysis of data of more than 200,000 patients who underwent CABG surgery found no evidence of a long-term increased risk of death with endoscopic vein graft harvesting compared to open vein-graft harvesting, according to a study in the August 1 issue of JAMA. The authors did find that the endoscopic technique was associated with a significant reduction in wound complications.

“In the mid-1990s, surgeons began using endoscopic vein-graft harvesting techniques as an alternative to large, incision-based open vein-graft harvesting to improve postoperative discomfort and incision-site complications,” according to background information in the article. “The perceived advantages of endoscopic vein-graft harvesting led to wide-spread adoption of the technique, and the devices have been used in the majority of the more than 400,000 CABG surgery procedures performed at U.S. surgical centers each year.” In 2009, a study that included 3,000 patients called into question the safety of the endoscopic vein-graft harvesting technique, finding that patients who received this procedure had higher 3-year mortality than those receiving open vein-graft harvesting technique.

Judson B. Williams, M.D., M.H.S., of Duke University Medical Center, Durham, N.C., and colleagues conducted a study to assess use of the endoscopic vein-graft harvesting technique in CABG surgery and the risk of death, heart attack, and repeat revascularization. The observational study included 235,394 Medicare patients undergoing isolated CABG surgery between 2003 and 2008 at 934 surgical centers participating in the Society of Thoracic Surgeons (STS) national database. The STS records were linked to Medicare files to allow longitudinal assessment (median [midpoint] 3-year follow-up) through December 31, 2008.

Based on Medicare Part B coding, 52 percent of patients received endoscopic vein-graft harvesting during CABG surgery. The researchers found no significant differences between the cumulative incidence rate for mortality through 3 years for the endoscopic (13.2 percent [12,429 events]) and open (13.4 percent [13,096 events]) vein-graft harvest groups. There were also no significant differences between the cumulative incidence through 3 years for the composite of death, heart attack, or revascularization among the endoscopic vs. open vein-graft harvest groups (19.5 percent [18,419 events] vs. 19.7 percent [19,232 events]).

Endoscopic vein-graft harvesting was associated with lower harvest site wound complications relative to open vein-graft harvesting (3.0 percent vs. 3.6 percent).

“Our study found that endoscopic vein-graft harvesting was the most commonly used technique for vein-graft harvesting, with approximately 70 percent of CABG surgery cases in the STS Adult Cardiac Surgery Database using this technique in 2008, the most recent year examined. After adjustment for baseline clinical factors, no evidence was found of increased long-term mortality or the composite of death, myocardial infarction, or revascularization associated with endoscopic vs. open vein-graft harvesting in isolated patients undergoing CABG surgery. Consistent with previous randomized comparisons, use of endoscopic vein-graft harvesting was associated with a significant reduction in wound complications relative to the open procedures,” the authors conclude.

(JAMA. 2012;308[5]:475-484. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Endoscopic Vein-Graft Harvest Is Safe for CABG Surgery

In an accompanying editorial, Lawrence J. Dacey, M.D., M.S., of the Dartmouth-Hitchcock Medical Center, Lebanon, N.H., comments on the findings of this study.

“Physicians tend to do what is best for their patients. Patient satisfaction is markedly better with endoscopic vein-graft harvesting. Patients who have had both an endoscopic and open vein-graft harvest marvel at the difference in reduced pain and time of healing with endoscopic vein-graft harvesting. This conclusive study by Williams et al provides information to say with certainty that the benefits of endoscopic vein-graft harvesting in short-term patient-centered outcomes are not associated with an increased risk of important adverse long-term outcomes. And that is something to be thankful for.”

(JAMA. 2012;308[5]:475-484. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 31, 2012

Media Advisory: To contact corresponding author Sapna Syngal, M.D., M.P.H., call Jessica Maki at 617-534-1603 or email jmaki3@partners.org. To contact editorial co-author Hemant K. Roy, M.D., call Jim Anthony at 847-570-6132 or email janthony@northshore.org.

CHICAGO – Among patients with multiple colorectal polyps, the prevalence of certain gene mutations varied considerably by polyp count, according to a study in the August 1 issue of JAMA.

“Patients with multiple colorectal adenomas [polyps] may carry germline [those cells of an individual that have genetic material that could be passed to offspring] mutations in the APC or MUTYH genes,” according to background information in the article. The authors write that guidelines for when genetic evaluation should be performed in individuals with multiple colorectal adenomas vary, and data to support such guidelines are limited.

Shilpa Grover, M.D., M.P.H., of Brigham and Women’s Hospital, Boston, and colleagues conducted a study to evaluate the frequency of APC and MUTYH mutations by the number of colorectal adenomas among individuals who had undergone clinical genetic testing. The researchers also studied the relationship between the number of adenomas and age at diagnosis of adenoma and colorectal cancer and the prevalence of pathogenic APC or MUTYH mutations.

The study included 8,676 individuals who had undergone full gene sequencing between 2004 and 2011. Individuals with a certain mutation of the MUTYH gene (Y179C and G396D) underwent full MUTYH gene sequencing. APC and MUTYH mutation prevalence was evaluated by the number of polyps.

Colorectal adenomas were reported in 7,225 individuals; 1,457 with classic polyposis (100 adenomas or more) and 3,253 with attenuated (diminished) polyposis (20-99 adenomas). “The prevalence of pathogenic APC and biallelic [pertaining to both alleles (both alternative forms of a gene)] MUTYH mutations was 95 of 119 (80 percent) and 2 of 119 (2 percent), respectively, among individuals with 1,000 or more adenomas, 756 of 1,338 (56 percent) and 94 of 1,338 (7 percent) among those with 100 to 999 adenomas, 326 of 3,253 (10 percent) and 233 of 3,253 (7 percent) among those with 20 to 99 adenomas, and 50 of 970 (5 percent) and 37 of 970 (4 percent) among those with 10 to 19 adenomas. Adenoma count was strongly associated with a pathogenic mutation in multivariable analyses,” the authors write.

The researchers note that their evaluation of individuals who underwent genetic testing because of a personal or family history suggestive of a familial polyposis syndrome suggests that genetic evaluation for APC and MUTYH mutations may be considered in individuals with 10 or more adenomas. “However, our results are derived from a selected cohort of high-risk individuals and need to be validated in larger populations of unselected patients.”

“The mutation probabilities reported here may assist clinicians in their decision to recommend genetic evaluation and counsel patients undergoing genetic testing. However, it remains important to also consider the limitations of genetic testing at present, because one-third of patients with a classic familial adenomatous polyposis [FAP; a polyposis syndrome resulting from mutations in the APC gene characterized by multiple colorectal polyps] phenotype are found to not carry a mutation in either the APC or MUTYH gene. Such individuals should undergo periodic re-evaluation as other susceptibility genes are identified.”

(JAMA. 2012;308[5]:485-492. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This study was supported by National Cancer Institute grants and by a National Institutes of Health grant. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: APC Gene Testing for Familial Adenomatosis Polyposis

“At this juncture, clinicians need to carefully consider the effect of a positive or negative test result on management of patient care prior to making decisions regarding genetic testing,” write Hemant K. Roy, M.D., and Janardan D. Khandekar, M.D., of the NorthShore University HealthSystem, Evanston, Il., in an accompanying editorial.

“Appropriate patient education and informed consent prior to testing is mandatory, highlighting the integral nature of genetic counseling. Until development of more robust genomic technologies for FAP detection, complementary approaches including careful assessment of family history and biomarkers may have utility. Furthermore, these considerations for FAP may serve as a model for evaluating the wider issues associated with practicing medicine at the front lines of the genomic revolution.”

(JAMA. 2012;308[5]:514-515. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 31, 2012

Media Advisory: To contact James A. Blumenthal, Ph.D., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

CHICAGO – Patients with chronic heart failure who participated in exercise training had modest reductions in symptoms of depression after 12 months, compared with usual care, according to a study in the August 1 issue of JAMA.

“An estimated 5 million people in the United States have heart failure, and more than 500,000 new cases are diagnosed annually,” according to background information in the article. Clinical depression is a common co-existing illness, affecting as many as 40 percent of patients with heart failure, with up to 75 percent of patients reporting elevated depressive symptoms. Depression also is associated with worse clinical outcomes in a variety of cardiac patient populations. “Some evidence suggests that aerobic exercise may reduce depressive symptoms, but to our knowledge the effects of exercise on depression in patients with heart failure have not been evaluated,” the authors write.

James A. Blumenthal, Ph.D., of Duke University Medical Center, Durham, N.C., and colleagues conducted a study to assess the effects of exercise on depressive symptoms and to determine whether reduced depressive symptoms were associated with improved clinical outcomes. The randomized controlled trial involved 2,322 stable patients treated for heart failure at 82 medical clinical centers in the United States, Canada, and France. A measure of depressive symptoms was gauged via a questionnaire (Beck Depression Inventory II [(BDI-II]). Depressive scores ranged from 0 to 59; scores of 14 or higher are considered clinically significant. Participants were randomized between April 2003 and February 2007 to receive either supervised aerobic exercise (goal of 90 min/week for months 1-3 followed by home exercise with a goal of ≥ 120 min/week for months 4-12) or to education and usual guideline-based heart failure care.

The median (midpoint) BDI-II score at study entry was 8; 28 percent of the sample had BDI-II scores of 14 or higher. Depression scores were available for 2,322 participants at the beginning of the study, 2,019 at month 3 and 1,738 at month 12. The researchers found that the adjusted 3-month BDI-II average score was 8.95 for the aerobic exercise group and 9.70 for usual care (a difference of -0.76). The adjusted BDI-II score at month 12 was 8.86 for the aerobic exercise group and 9.54 for usual care (a difference of -0.68).

The authors observed similar results when they examined the treatment effects within the subset of patients with clinically significant depressive symptoms (baseline BDI-II scores >14), with BDI-II scores at 3 and 12 months lower for patients in the aerobic exercise group than for patients in usual care group.

Patients within the aerobic exercise group who reported greater adherence to the exercise prescription achieved relatively larger reductions in depressive symptoms, although the absolute reduction was small.

The researchers also observed that elevated depressive symptoms were associated with more than a 20 percent increase in risk for all-cause mortality and hospitalizations and that the increased risk was independent of antidepressant use and established risk factors in patients with heart failure including age and disease severity.

(JAMA. 2012;308[5]:465-474. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 31, 2012

Media Advisory: To contact corresponding author Anne L. Coleman, M.D., Ph.D., call Elaine Schmidt at 310-794-2272 or email eschmidt@mednet.ucla.edu.

CHICAGO – Medicare patients 65 years and older who underwent cataract surgery had a lower odds of hip fracture 1 year after the procedure when compared with patients with cataract who did not have cataract surgery, according to a study in the August 1 issue of JAMA.

Visual impairment has been found to be strongly associated with an increased risk of fractures, a significant cause of illness and death in the elderly population. “Specifically, vision plays an important role in providing a reference frame for postural balance and stability, and cataract-induced changes in vision have been found to be associated with postural instability,” according to background information in the article. “Furthermore, cataracts have been found to be the most common cause of fracture-related visual impairment, with untreated cataract causing up to 49 percent of visual impairment in patients with femoral neck fractures related to decreased vision.” Despite the association of poor vision and cataracts with increased fall and fracture risk, only a limited number of studies have examined the influence of cataract surgery on fall incidence in visually impaired adults.

Victoria L. Tseng, M.D., of the Warren Alpert Medical School of Brown University, Providence, R.I., and colleagues examined the association between cataract surgery and fracture incidence at 1-year. The study included a 5 percent random sample of Medicare Part B beneficiaries with cataract who received and did not receive cataract surgery from 2002 through 2009. Analyses were adjusted for various factors.

There were 1,113,640 Medicare beneficiaries 65 years and older with a diagnosis of cataract between 2002 and 2009 in the 5 percent random sample. Of these patients, the majority were female (60 percent) and white (88 percent). Of patients with cataract, 410,809 (36.9 percent) underwent cataract surgery during the study period. During this period, the overall 1-year fracture incidence was 1.3 percent (n = 13,976) for hip fractures. Analysis of the data indicated that cataract surgery was associated with a 16 percent decrease in the adjusted odds of hip fracture 1 year after the procedure. “In patients with severe cataract, the association between cataract surgery and lower odds of hip fracture was even stronger, with a 23 percent reduction in the adjusted odds of hip fracture in the cataract surgery group compared with the cataract diagnosis group,” the authors write.

Osteoporosis was the most common fracture-related comorbidity (co-existing illness) (12.1 percent). The most common ocular comorbidity was glaucoma (19.1 percent).

“Cataract surgery may be associated with lower odds of subsequent fracture in patients aged 65 years and older in the U.S. Medicare population. Future prospective studies using standardized registries of patients with cataracts will help further elucidate the association between cataract surgery and fracture risk. Cataract surgery has already been demonstrated to be a cost-effective intervention for visual improvement, with an estimated cost per quality-adjusted life-year gained for cataract surgery in the first eye of $2,023 in the United States and $2,727 in the second eye. The results in this study suggest the need for further investigation of the additional potential benefit of cataract surgery as a cost-effective intervention to decrease the incidence of fractures in the elderly,” the researchers conclude.

(JAMA. 2012;308[5]:493-501. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This study was supported by the Center for Eye Epidemiology, Jules Stein Eye Institute. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, July 31 at this link.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (ET) SUNDAY, JULY 22, 2012

Use of Hydroxychloroquine Does Not Slow HIV Disease Progression Among Patients Not Taking Antiretroviral Therapy

Nicholas I. Paton, M.D., F.R.C.P., of the MRC Clinical Trials Unit, London, and colleagues conducted a study to examine whether hydroxychloroquine decreases immune activation and inflammation and subsequently slows the progression of early HIV disease. Hydroxychloroquine is a drug that has immunomodulatory and anti-inflammatory properties and has been reported to have anti-HIV properties in vitro.

“International HIV treatment guidelines recommend that antiretroviral therapy should be started when the CD4 cell count reaches 350 cells/µL, but resource limitations prevent implementation of this recommendation in many countries. An inexpensive, safe, and well-tolerated intervention that slowed the rate of decline of CD4 cells (and thereby delayed the time of starting combination antiretroviral therapy) would therefore be attractive,” according to background information in the article.

The randomized, placebo-controlled trial was performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/µL. Patients received hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks.

The researchers found that “hydroxychloroquine did not decrease immune activation but had a detrimental effect on CD4 cell count and increased HIV viral replication in patients with chronic HIV infection who were not receiving antiretroviral therapy. Alternative interventions are needed to reduce immune activation and disease progression in early HIV infection.”

(JAMA. 2012;308[4]:353-361. Available pre-embargo to the media at http://media.jamanetwork.com)

To contact Nicholas I. Paton, M.D., F.R.C.P., email nick.paton@ctu.mrc.ac.uk.

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 Liver Disease Stage Associated With Risk of Liver-Related Complications and Death Among Persons Infected With HIV and Hepatitis C

Berkeley N. Limketkai, M.D., of the Johns Hopkins University School of Medicine, Baltimore, and colleagues conducted a study to determine the rates of end-stage liver disease (ESLD), hepatocellular carcinoma (HCC), or death (all-cause and liver-related mortality) among human immunodeficiency virus/hepatitis C virus coinfected adults.

“Hepatitis C virus (HCV) coinfection occurs frequently in persons infected with the human immunodeficiency virus (HIV) because of shared routes of acquisition,” according to background information in the article. “Human immunodeficiency virus accelerates hepatitis C virus disease progression; however, the effect of liver disease stage and antiviral therapy on the risk of clinical outcomes is incompletely understood.”

The study included 638 coinfected adults (80 percent black, 66 percent men) receiving care at the Johns Hopkins HIV clinic and receiving a liver biopsy and who were prospectively monitored for clinical events between July 1993 and August 2011 (median [midpoint] follow-up, 6 years). Histological specimens were analyzed for hepatic fibrosis stage.

The researchers found that patients experienced a graded increased risk in incidence of clinical outcomes based on baseline hepatic fibrosis stage. “Importantly, we found that HIV treatment with antiretroviral therapy, higher CD4 cell count, and effective HCV treatment were associated with significantly lower risk of clinical outcomes including those related to liver disease in some cases. As such, our findings have potential implications with respect to liver disease staging and initiation of antiviral therapy for coinfected persons.”

(JAMA. 2012;308[4]:370-378. Available pre-embargo to the media at http://media.jamanetwork.com)

To contact corresponding author Mark S. Sulkowski, M.D., call David March at 410-955-1534 or email dmarch1@jhmi.edu.

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Patients With HIV Appear More Likely To Have Increased Inflammation of Arterial Walls, Which Increases Risk For Cardiovascular Disease

Sharath Subramanian, M.D., of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues examined whether arterial wall inflammation is increased in patients with HIV compared with patients not infected with HIV with similar cardiac risk factors.

“Coronary artery disease (CAD) is significantly increased in patients infected with human immunodeficiency virus (HIV), but the specific mechanisms remain unknown,” according to background information in the article.

The study, which included 81 participants, was conducted from November 2009 through July 2011. Twenty-seven participants with HIV without known cardiac disease underwent a cardiac imaging test (¹⁸fluorine-2-deoxy-D-glucose positron emission tomography [¹⁸F-FDG-PET]) for assessment of arterial wall inflammation and coronary computed tomography scanning for coronary artery calcium. The HIV group was compared with 2 separate non-HIV control groups. One control group (n=27) was matched to the HIV group for age, sex, and Framingham risk score (FRS; a measure of cardiovascular risk) and had no known atherosclerotic disease (non-HIV FRS-matched controls). The second control group (n=27) was matched on sex and selected based on the presence of known atherosclerotic disease (non-HIV atherosclerotic controls).

The researchers found that HIV infection was associated with a high degree of inflammation within the arterial wall, even in patients with low FRS and well-controlled viremia. “These findings advance our understanding of the unique pathophysiology and predilection to early increased CVD among patients infected with HIV …” the authors write. “These data have clinical relevance and suggest that patients with HIV with chronic infection have significant vascular inflammation, and thus added CVD risk, beyond that estimated by traditional risk factors. This information should now be considered in determining optimal monitoring and CVD prevention strategies for this group.”

(JAMA. 2012;308[4]:379-386. Available pre-embargo to the media at http://media.jamanetwork.com)

To contact corresponding author Steven K. Grinspoon, M.D., call Sue McGreevey at 617-724-2764 or email smcgreevey@partners.org.

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Proportion of Patients Receiving Antiretroviral Therapy With Sustained Viral Suppression Increases Over Past Decade

Baligh R. Yehia, M.D., M.S.H.P., M.P.P., of the University of Pennsylvania Perelman School of Medicine, Philadelphia, and colleagues conducted a study to examine the change in and determinants of sustained viral suppression over time in HIV-infected adults receiving antiretroviral therapy (ART).

As reported in a Research Letter, the study included HIV-infected adults who initiated care at 12 high-volume HIV clinics that are part of the HIV Research Network (HIVRN). Clinics are located in the Northeastern (n = 6), Midwestern (n = l), Southern (n = 2), and Western (n = 3) sections of the United States. Patients were offered enrollment in the HIVRN. A total of 32,483 patients received care at the 12 clinics between 2001 and 2010.

The researchers found that the percentage of patients receiving ART with sustained viral suppression increased from 45 percent in 2001 to 72 percent in 2010. “Sustained viral suppression was lower for blacks and injection drug users during all 10 years. Older individuals and those with private insurance were more likely to have sustained viral suppression compared with younger patients and those with Medicaid, Medicare, or who were uninsured.”

The authors write that new drugs and combination fixed-dose tablets have enhanced the efficacy, safety, and tolerability of regimens. “Better access to care and adherence to treatment may also have contributed to improved virologic suppression.”

(JAMA. 2012;308[4]:339-342. Available pre-embargo to the media at http://media.jamanetwork.com)

Viewpoints in This Week’s JAMA

HIV/AIDS in 1990 and 2012 – From San Francisco to Washington, D.C.

Robert Steinbrook, M.D., of the Yale School of Medicine, New Haven, Conn., examines the changes in treatments and policies for HIV/AIDS that have occurred since the last time the International AIDS Conference was held in the U.S., in 1990, to this month’s conference in Washington, D.C.

Dr. Steinbrook discusses the successes and disappointments over this time period, including the advent of highly active antiretroviral therapy, and the absence of an AIDS vaccine.

(JAMA. 2012;308[4]:345-346. Available pre-embargo to the media at http://media.jamanetwork.com)

The Future of HIV Prevention in the United States

Jonathan Mermin, M.D., M.P.H., and Kevin A. Fenton, M.D., Ph.D., of the Centers for Disease Control and Prevention, Atlanta, write that in the last 15 years, there’s been a 60 percent increase of the number of people in the U.S. living with HIV, to 1.1 million people. “The increasing number of people who can potentially transmit HIV makes prevention more difficult.”

In this Viewpoint, the authors discuss challenges and strategies of HIV prevention efforts in the U.S. “The United States has an opportunity to shift from supporting hundreds of different HIV prevention approaches to objectively assessing current HIV strategies, focusing on more cost-effective activities, and conducting research that will establish the groundwork for the future. This shift should help improve the effectiveness of HIV prevention efforts, reduce HIV incidence, and ultimately increase the possibility of achieving an AIDS-free America.”

(JAMA. 2012;308[4]:347-348. Available pre-embargo to the media at http://media.jamanetwork.com)

Aging and HIV-Related Cognitive Loss

Farrah J. Mateen, M.D., of Johns Hopkins University, Baltimore, and Edward J. Mills, Ph.D., of the University of Ottawa, Ontario, Canada, write that cognitive disorders related to HIV remain an important burden of disease and disability worldwide, and that conservative estimates from better resourced countries suggest that the number of individuals of all ages living with HIV-related cognitive disorders will increase 5- to 10- fold by 2030.

The authors add that complicating HIV-related neurocognitive disorders is older age, which is the major risk factor for multiple forms of cognitive decline. They discuss strategies needed to address the issues related to aging and HIV-related cognitive decline. “An improved understanding of cognitive function in individuals with HIV infection would promote a better understanding of the epidemic of cognitive decline and provide an opportunity for scientific and community discussion on interventions that can be offered in a culturally relevant manner.”

(JAMA. 2012;308[4]:349-350. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (ET) SUNDAY, JULY 22, 2012

Media Advisory: To contact Anthony S. Fauci, M.D., call Kathy Stover at 301-402-1663 or email Kathy.stover@nih.gov.

WASHINGTON, D.C. – Ending the global HIV/AIDS pandemic may be possible by implementing a multifaceted global effort that expands testing, treatment, and prevention programs, as well as meets the scientific challenges of developing an HIV vaccine and possibly a cure, according to a Viewpoint in the July 25 issue of JAMA, a theme issue on HIV/AIDS.

Anthony S. Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Md., presented the article at a JAMA media briefing at the International AIDS Conference.

Dr. Fauci and co-author Gregory K. Folkers, M.S., M.P.H., also of the NIAID, write that “since the first cases of what is now known as AIDS were reported in 1981, an entire generation has grown up under the constant cloud of this modern-day plague. Across the globe, more than 34 million people are living with the human immunodeficiency virus (HIV), the virus that causes AIDS, including approximately 1.2 million individuals in the United States. HIV/AIDS has been responsible for the deaths of an estimated 30 million individuals.” They add that although the rate of new HIV infections has declined or stabilized in many countries, the disease continues to exact an enormous toll: 1.8 million deaths in 2010 alone, and grief and hardship for countless families and communities.

Because powerful interventions have been developed and scientifically proven effective, the fight against HIV/AIDS is currently viewed with considerably more optimism than in past years, the authors write. “If these tools are made widely available to those who need them, an AIDS-free generation may be possible—that is, today’s children could one day live in a world in which HIV infections and deaths from AIDS are rare.”

Among the most important interventions is combination antiretroviral therapy, which significantly improves the health and longevity of individuals infected with HIV. “Since the advent of antiretroviral therapy, the annual number of deaths due to AIDS has decreased by two-thirds in the United States. Globally, an estimated 700,000 lives were saved in 2010 alone due to the increased availability of antiretroviral therapy in low- and middle-income countries,” the authors write. “Important challenges remain—notably finding the resources and developing the infrastructure to provide antiretroviral therapy to the estimated 8 million individuals with HIV infection who need these drugs but are not receiving them.”

The authors add that antiretroviral therapy can also prevent HIV infection by reducing the amount of virus in an infected person’s blood and other body fluids, making it less likely that the virus will be transmitted to others. Also, antiretroviral therapy is highly effective in blocking mother-to-child HIV transmission.

Other important interventions include medical male circumcision, which offers a highly effective and durable way to protect heterosexual men from HIV infection; and potentially, pre-exposure prophylaxis with antiretroviral medications, which have shown promise in reducing an individual’s risk of acquiring HIV infection.

“Each of these treatment and prevention strategies has a strong evidence base; with further refinement and scale-up and also when used in combination, they could have an extraordinary effect on decreasing the trajectory of the HIV pandemic.”

According to the authors, researchers are maintaining focus on 2 key scientific challenges that remain: the development of a vaccine and a cure. They write that modest success in a large-scale clinical trial of an HIV vaccine, promising results in animal models, and advances in structure-based vaccine design suggest that an HIV vaccine is feasible. The prospect of an HIV cure remains challenging.

The authors conclude that ending the global HIV/AIDS pandemic “will require a global commitment of resources involving additional donor countries, strengthening health care systems overall, and fostering greater ownership by host countries of HIV/AIDS effort, including investing more in the health of their people. With collective and resolute action now and a steadfast commitment for years to come, an AIDS-free generation is indeed within reach.”

(JAMA. 2012;308[4]:343-344. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Both authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (ET) SUNDAY, JULY 22, 2012

Media Advisory: To contact H. Irene Hall, Ph.D., call the National Center for HIV/AIDS, Viral Hepatitis, STD and TB Prevention press office at 404-639-8895 or email NCHHSTPMediaTeam@cdc.gov.

WASHINGTON, D.C. – An examination of the characteristics of persons born outside the United States diagnosed with HIV while living in the U.S. finds that, compared to U.S.-born persons with HIV, they are more likely to be Hispanic or Asian, and to have a higher percentage of HIV infections attributed to heterosexual contact, according to a study appearing in JAMA being published online.

H. Irene Hall, Ph.D., of the Centers for Disease Control and Prevention, Atlanta, presented the findings of the study at a JAMA media briefing at the International AIDS Conference.

“Persons born outside the United States comprise approximately 13 percent of the total U.S. population and represent a varied group of people, including students, skilled workers, family members of U.S. citizens, undocumented migrants, naturalized citizens, and refugees,” according to background information in the article. “Although more than 95 percent of persons with HIV in the world live outside the United States, an understanding of HIV infection in persons born outside but living in the United States allows for both a new perspective on HIV in this country as well as a better understanding of the health status and health education needs of persons born outside the United States.” The authors add that it can be difficult for persons born outside the United States to learn about HIV prevention, access HIV testing, and obtain timely medical care because of language and cultural barriers.

Dr. Hall and colleagues examined the demographic, geographic, and risk factor characteristics of U.S.-born and persons born outside the U.S. who received a diagnosis of HIV while living in the U.S. from 2007 through 2010 in 46 states and 5 U.S. territories, as reported to the National HIV Surveillance System. The category of persons were defined as persons born outside the United States and its territories was inclusive of naturalized citizens.

The researchers found that from 2007 through 2010, a total of 191,697 persons received a diagnosis of HIV. Of these, 30,995 (16.2 percent) were born outside the United States. The 4 states (California, Florida, New York, and Texas) reporting the highest numbers of persons born outside the U.S. and diagnosed with HIV were also the top 4 states with HIV cases overall. The majority of HIV cases occurred in males (n = 124,863 [77.7 percent] among U.S.-born males vs. n = 22,773 [73.5 percent] among males born outside the United States).

Regarding race/ethnicity, the researchers found that the proportion of persons born outside the United States varied by category. “Of the 55,574 HIV diagnoses in whites, 1,841 (3.3 percent) were in persons born outside the U.S.; of 86,547 diagnoses in blacks, 8,614 (10.0 percent) were in persons born outside the U.S. Of the 42,431 HIV diagnoses in Hispanics, 17,913 (42.2 percent) were in persons born outside the U.S. Of 3,088 HIV diagnoses in Asians, 1,987 (64.3 percent) were in persons born outside the U.S.”

Overall, 39.4 percent of HIV diagnoses in persons born outside the United States (men and women combined) were attributed to heterosexual contact; for U.S.-born persons, 27.2 percent was due to heterosexual contact.  For both males born outside the U.S. and U.S.-born men, the majority of HIV diagnoses were in men who have male-to-male sexual contact.

Of the 25,255 persons diagnosed with HIV with a specified country or region of birth outside the United States, the most common region of birth origin was Central America (including Mexico; n = 10,343 [41.0 percent]), followed by the Caribbean (n = 5,418; 21.5 percent), Africa (n = 3,656; 14.5 percent), Asia (n = 1,995; 7.9 percent), and South America (n = 1,929; 7.6 percent).

The researchers note that the date of first entry into the United States is not collected on the HIV case report form, so it is not possible to know whether HIV infection preceded or followed immigration.

“These findings demonstrate the diversity of the HIV-infected population born outside the United States, presenting many clinical and public health challenges,” the authors conclude.

(doi:10.1001/JAMA.2012.9046. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The Centers for Disease Control and Prevention funds all states and the District of Columbia to conduct HIV surveillance and selected areas to conduct HIV incidence surveillance and provides technical assistance to all funded areas. The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 10 a.m. ET Sunday, July 22 at this link.

Editorial: HIV Infection Among Persons Born Outside the United States

Mitchell H. Katz, M.D., of the Los Angeles County Department of Health Services, and Deputy Editor, Archives of Internal Medicine, writes in an accompanying editorial that the findings of this study “suggests that persons born outside the United States who reside in the United States are a heterogeneous group.”

“This study and other studies suggest that these persons are in need of appropriate education and outreach, testing and treatment, and mental health services including specialized services for those who experience traumatic events in their home countries or during the immigration process, substance treatment for those addicted to drugs, as well as HIV care for those who are infected. Although these lessons may apply regardless of country of origin for HIV-infected persons, the effectiveness of these messages and interventions will require culturally relevant delivery to each specific population of immigrants.”

(doi:10.1001/JAMA.2012.8670. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Katz reported serving as a consultant to ETR Associates Inc., and receiving royalties for a chapter on HIV/AIDS in Current Medical Diagnosis and Treatment.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (ET) SUNDAY, JULY 22, 2012

Media Advisory: To contact Howard D. Strickler, M.D., M.P.H., call Deirdre Branley at 347-266-9204 or email sciencenews@einstein.yu.edu.

WASHINGTON, D.C. – HIV-infected and uninfected women with normal cervical cytology (Pap test) and a negative test result for oncogenic (tumor inducing) human papillomavirus DNA at study enrollment had a similar risk of cervical precancer and cancer after 5 years of follow-up, according to a study in the July 25 issue of JAMA, a theme issue on HIV/AIDS.

Howard D. Strickler, M.D., M.P.H., of the Albert Einstein College of Medicine of Yeshiva University, New York, presented the findings of the study at a JAMA media briefing at the International AIDS Conference.

“U.S. cervical cancer screening guidelines for human immunodeficiency virus (HIV)-uninfected women 30 years or older have recently been revised, increasing the suggested interval between Papanicolaou (Pap) tests from 3 years to 5 years among those with normal cervical cytology results who test negative for oncogenic human papillomavirus (HPV). Whether a 3-year or 5-year screening interval could be used in HIV-infected women who are cytologically normal and oncogenic HPV-negative is unknown,” according to background information in the article.

Dr. Strickler and colleagues conducted a study to examine the 3-year and 5-year risk of cervical precancer and cancer defined by cytology (i.e., high-grade squamous intraepithelial lesion or greater [HSIL+]) and histology (cervical intraepithelial neoplasia 2 or greater [CIN-2+]), in HIV-infected women (n = 420) and HIV-uninfected women (n = 279). The participants, who at the beginning of the study had a normal Pap test result and were negative for oncogenic HPV, were enrolled in a multi-institutional U.S. cohort of the Women’s Interagency HIV Study, between October 2001 and September 2002, with follow-up through April 2011. Semiannual visits at 6 clinical sites included Pap testing and, if indicated, cervical biopsy.

Overall, no oncogenic HPV was detected in 369 (88 percent) of the HIV-infected women and 255 (91 percent) of the HIV-uninfected women with normal cervical cytology at enrollment. Two cases of HSIL+ were observed during the 5 years of observation, 1 among the HIV-uninfected women and 1 among the HIV-infected women with a CD4 cell count of 500 cells/µL or greater. Overall, the cumulative incidence of HSIL+ was 0.3 percent in HIV-infected women and 0.4 percent in HIV-uninfected women.

Based on a total of 15 cases, the authors found that the cumulative incidence of CIN-2+ over 5 years of follow-up was 2 percent in HIV-infected women with CD4 cell count less than 350 cells/µL, 2 percent in those with CD4 cell count of 350 to 499 cells/µL, 6 percent in those women with CD4 cell count of 500 cells/µL or greater, and 5 percent in HIV-uninfected women.

When the researchers combined the data among HIV-infected women, they found that the overall 5-year cumulative incidence of CIN-2+ in HIV-infected women was 5 percent. “Of the CIN-2+ cases, 2 were CIN-3 (an HIV-infected woman with a baseline CD4 cell count of 350-499 cells/µL, and an HIV-uninfected woman). The overall 5-year cumulative incidence of CIN-3+ was 0.5 percent in HIV-infected women and 0.7 percent in HIV-uninfected women. No cancers were observed.”

“In summary, the results of this prospective study suggest that HIV-infected women undergoing long-term clinical follow-up who are cytologically normal and oncogenic HPV-negative have a risk of cervical precancer similar to that in HIV-uninfected women through 5 years of follow-up. Additional observational studies or a randomized clinical trial may be necessary before clinical guideline committees consider whether to expand current recommendations regarding HPV co-testing to HIV-infected women. More broadly, the current investigation highlights the potential for a new era of molecular testing, including HPV as well as other biomarkers, to improve cervical cancer screening in HIV-infected women,” the authors conclude.

(JAMA. 2012;308[4]:362-369. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR EARLY RELEASE: 10 A.M. (ET) SUNDAY, JULY 22, 2012

Media Advisory: To contact Melanie A. Thompson, M.D., email drmt@mindspring.com, or contact Donna Jacobsen, Executive Director of IAS-USA at DJacobsen@iasusa.org or 415-544-9400.

WASHINGTON, D.C. – Included in the 2012 International Antiviral Society-USA panel recommendations for human immunodeficiency virus (HIV) patient care is that all adult patients, regardless of CD4 cell count, should be offered antiretroviral therapy (ART), according to an article in the July 25 issue of JAMA, a theme issue on HIV/AIDS. Other new recommendations include changes in therapeutic options and modifications in the timing and choice of ART for patients with an opportunistic illness such as tuberculosis.

Melanie A. Thompson, M.D., of the AIDS Research Consortium of Atlanta, presented the findings of the article at a JAMA media briefing at the International AIDS Conference.

“Since the first antiretroviral drug was approved 25 years ago, improvements in the potency, tolerability, simplicity, and availability of ART have resulted in dramatically reduced numbers of opportunistic diseases and deaths where ART is accessible,” according to background information in the article. “New trial data and drug regimens that have become available in the last 2 years warrant an update to guidelines for ART in HIV-infected adults in resource-rich settings.”

Dr. Thompson and colleagues with the International Antiviral Society-USA panel conducted a review of the medical literature to identify relevant evidence published since the last report (2010), as well as data that had been published or presented in abstract form at scientific conferences in the past 2 years. The revised guidelines reflect new data regarding recommendations of when to initiate ART, new options for initial and subsequent therapy, ART management in the setting of special conditions, new approaches to monitoring treatment success and quality, and managing antiretroviral failure.

Among the primary recommendations of the panel are that treatment is recommended for all adults with HIV infection. The researchers found that there is no CD4 cell count threshold at which starting therapy is contraindicated, but the strength of the recommendation and the quality of the evidence supporting initiation of therapy increase as the CD4 cell count decreases and when certain concurrent conditions are present. Patients should be monitored for their CD4 cell count, and also HIV-1 RNA levels, ART adherence, HIV drug resistance, and quality-of-care indicators.

Initial regimens that are recommended include 2 nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine) plus a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir or darunavir), or an integrase strand transfer inhibitor (raltegravir). “The aim of therapy continues to be maximal, lifelong, and continuous suppression of HIV replication to prevent emergence of resistance, facilitate optimal immune recovery, and improve health” the authors write. Alternatives in each class are recommended for patients with or at risk of certain concurrent conditions, including cardiovascular disease, reduced kidney function, or tuberculosis.

The primary reasons for switching regimens include virologic, immunologic, or clinical failure and drug toxicity or intolerance. Switching regimens in virologically suppressed patients to reduce toxicity, improve adherence and tolerability, and avoid drug interactions can be done by switching 1 or more agents in the regimen. “Confirmed treatment failure should be addressed promptly and multiple factors considered,” the researchers write.

“Although it is crucial to intensify efforts to find a cure for persons who are already infected and an effective vaccine for those who are not, many of the tools needed to control the HIV/AIDS pandemic are already at hand. Critical components of the tool kit to eradicate AIDS include expanded HIV testing, increased focus on engagement in HIV care, early and persistent access to ART, and attention to improving ART adherence. These must occur in the context of strategies to address social determinants of health, including the elimination of stigma and discrimination,” the authors conclude.

(JAMA. 2012;308[4]:387-402. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 17, 2012

Is It Time to Replace the Tuberculin Skin Test With a Blood Test?

“Recent mathematical tuberculosis (TB) transmission modeling has shown that substantial improvements in addressing latent tuberculosis infection (LTBI) will be needed to eliminate TB before the 22nd century,” writes Philip A. LoBue, M.D., and Kenneth G. Castro, M.D., of the Centers for Disease Control and Prevention, Atlanta. They add that effective management of LTBI has been hampered by limitations of both treatment regimens and diagnostic tools, and that there have been efforts at finding a replacement for the tuberculin skin test, which despite its many limitations has been the mainstay of LTBI diagnosis. In this Viewpoint, the authors compare the advantages and disadvantages of TB testing methods currently available.

(JAMA. 2012;308[3]:241-242. Available pre-embargo to the media at http://media.jamanetwork.com)

Understanding Health Care as a Complex System – The Foundation for Unintended Consequences

Lewis A. Lipsitz, M.D., of Harvard Medical School, Boston, writes that “to help guide future policies and avoid the unanticipated consequences of regulation, policy makers and physicians need to understand health care as a complex system and apply the principles of complexity science to achieve its goals.”

“The U.S. health care system will need to continue to depart from a mechanical, regulatory approach to health care policy and move toward a complex systems approach that permits creative self-organization. This may be accomplished by removing structural boundaries between health care professionals, aligning their goals, enabling experimentation, and establishing simple rules to help limit costs.”

(JAMA. 2012;308[3]:243-244. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 17, 2012

Media Advisory: To contact Bruce E. Landon, M.D., M.B.A., call David Cameron at 617-432-0441 or email david_cameron@hms.harvard.edu. To contact editorial co-author Elliott S. Fisher, M.D., M.P.H., call Annmarie Christensen at 603-653-0897 or email Annmarie.Christensen@dartmouth.edu.

CHICAGO – Physicians tend to share patients with colleagues who have similar personal traits and practice styles, and there is substantial variation in physician network characteristics across geographic areas, according to a study in the July 18 issue of JAMA.

Physicians are embedded in informal networks that result from their sharing of patients, information, and behaviors. “These informal information-sharing networks of physicians differ from formal organizational structures (such as a physician group associated with a health plan, hospital, or independent practice association) in that they do not necessarily conform to the boundaries established by formal structures,” according to background information in the article. “The potential influence of informal networks of physicians on decision making has been understudied despite the potential importance of these networks in day-to-day practice.”

Bruce E. Landon, M.D., M.B.A., of Harvard Medical School, Boston, and colleagues conducted a study to identify professional networks among physicians, examine how such networks vary across geographic regions, and determine factors associated with physician connections. Using methods adopted from social network analysis, Medicare administrative data from 2006 were used to study 4,586,044 Medicare beneficiaries seen by 68,288 physicians practicing in 51 hospital referral regions (HRRs). Distinct networks depicting connections between physicians (defined based on shared patients) were constructed for each of the 51 HRRs. The randomly sampled HRRs are distributed across all regions of the country and include urban and rural locations. The average physician age was 49 years and about 80 percent were male. Among the Medicare patients, the average age was 71 years and 40 percent were male.

Substantial variation was observed across HRRs. The number of included physicians ranged from 135 in Minot, N.D., (1,568 ties) to 8,197 in Boston (392,582 ties). The average adjusted degree (number of other physicians each physician was connected to per 100 Medicare beneficiaries) across all HRRs was 27.3. Patterns varied by physician specialty as well. Physicians with ties to each other were far more likely to be based at the same hospital (69.2 percent of unconnected physician pairs vs. 96.0 percent of connected physician pairs). Connected physician pairs also were more likely to be in close geographic proximity. The average distance for connected pairs was 13.1 miles vs. 24 miles.

“Characteristics of physicians’ patient populations also were associated with the presence of ties between physicians.  Across all racial and ethnic groups, connected physicians had more similar racial compositions of their patient panels than unconnected physicians. For instance, connected physician pairs had an average difference of 8.8 points in the percentage of black patients in their 2 patient panels compared with a difference of 14.0 percentage points for unconnected physician pairs. Similarly, differences in mean [average] patient age and percentage of Medicaid patients also were smaller for connected physicians than unconnected physicians. Medical comorbidities [co-existing illnesses] were also more similar, suggesting that connected physicians had more similar patients in terms of clinical complexity than unconnected physicians,” the authors write. “Physicians thus tend to cluster together along attributes that characterize their own backgrounds and the clinical circumstances of their patients.”

“It has long been known that physician behavior varies across geographic areas, yet our understanding of the factors that contribute to these geographic differences is incomplete. Our findings suggest that variation according to network attribute might help explain health care variation across geographic areas, particularly given what is known about how networks function.”

“In conclusion, we used novel methods to define social networks among physicians in geographic areas based or shared patients, examined how such networks vary across different geographic regions, and identified physician and patient population factors that are associated with physician patient-sharing relationships. This approach might have useful applications for policy makers seeking to influence physician behavior (whether related to accountable care organizations or innovation adoptions) because it is likely that physicians are strongly influenced by their network of relationships with other physicians,” the researchers write.

(JAMA. 2012;308[3]:265-273. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This work was supported by a grant from the National Institute on Aging. Dr. Barnett was supported by a Doris Duke Charitable Foundation Clinical Research Fellowship and a Harvard Medical School Research Fellowship. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Editorial: Social Networks in Health Care – So Much to Learn

In an accompanying editorial, Valerie A. Lewis, Ph.D., and Elliott S. Fisher, M.D., M.P.H., of Dartmouth Medical School, Hanover, N.H., discuss the importance of networks in health care.

“As advances in biomedicine enhance the effectiveness and complexity of the medical interventions required to treat acute and chronic illness, it is becoming clear that meeting physicians’ professional responsibility to each patient will require new ways of working together. Evidence from fields outside medicine, summarized in Putnam’s ‘Bowling Alone,’ concludes that stronger connections within a given group (such as physicians) and across groups (such as between physicians, nurses, and administrators) can help create the trust and shared values that are crucial to organizational success and individual fulfillment. Further research along the lines developed by Landon and colleagues should help bring useful insights to health care.”

(JAMA. 2012;308[3]:294-296. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 17, 2012

Media Advisory: To contact Michael W. Fried, M.D., call Tom Hughes at 919-966-6047 or email tahughes@unch.unc.edu.

CHICAGO – Use of the botanical product silymarin, an extract of milk thistle that is commonly used by some patients with chronic liver disease, did not provide greater benefit than placebo for patients with treatment-resistant chronic hepatitis C virus (HCV) infection, according to a study in the July 18 issue of JAMA.

Chronic hepatitis C virus infection affects almost 3 percent of the global population and may lead to cirrhosis, liver failure, and liver cancer. A large proportion of patients do not respond to certain treatments for this infection, and many others cannot be treated because of co-existing illnesses. “Thus, alternative medications with disease-modifying activity may be of benefit,” according to background information in the article. Thirty-three percent of patients with chronic HCV infection and cirrhosis reported current or past use of silymarin for the treatment of their disease. Clinical studies that have evaluated milk thistle for a variety of liver diseases have yielded inconsistent results.

Michael W. Fried, M.D., of the University of North Carolina, Chapel Hill, and colleagues conducted a study to assess the use of silymarin for treating chronic HCV infection. The multicenter, placebo-controlled trial was conducted at 4 medical centers in the United States. Participants included 154 persons with chronic HCV infection and serum alanine aminotransferase (ALT; an enzyme that reflects liver function) levels of 65 U/L or greater who were previously unsuccessfully treated with interferon-based therapy. Enrollment began in May 2008 and was completed in May 2010, with the last follow-up visit completed in March 2011. Participants were randomly assigned to receive 420-mg silymarin, 700-mg silymarin, or matching placebo administered 3 times per day for 24 weeks. The primary outcome measure for the study was a serum ALT level of 45 U/L or less (considered within the normal range) or less than 65 U/L, provided this was at least a 50 percent decline from baseline values. Secondary outcomes included changes in ALT levels, HCV RNA levels, and quality-of-life measures.

At the end of treatment, only 2 participants in each treatment group achieved the prespecified primary end point. The percentages of participants who achieved the primary end point were 3.8 percent in the placebo group, 4.0 percent in the 420-mg silymarin group, and 3.8 percent in the 700-mg silymarin group. The researchers also found that there was no statistically significant difference across treatment groups when changes in serum ALT levels from the beginning of the study to end of treatment were analyzed. Also, average serum HCV RNA levels did not change significantly during the 24 weeks of therapy.

There were no significant changes in physical or mental health components of quality-of-life scores, in chronic liver disease health-related quality-of-life assessments, or in depression scores in any group. Frequency of adverse events reported by individual patients also did not differ significantly among the treatment groups.

“In summary, oral silymarin, used at higher than customary doses, did not significantly alter biochemical or virological markers of disease activity in patients with chronic HCV infection who had prior treatment with interferon-based regimens,” the authors conclude.

(JAMA. 2012;308[3]:274-282. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 17, 2012

Media Advisory: To contact Gregg C. Fonarow, M.D., call Rachel Champeau at 310-794-2270 or email RChampeau@mednet.ucla.edu. To contact editorial co-author Tobias Kurth, M.D., Sc.D., email tobias.kurth@univ-bordeaux.fr.

CHICAGO – Adding stroke severity to a hospital 30-day mortality model based on claims data for Medicare beneficiaries with acute ischemic stroke was associated with improvement in predicting the risk of death at 30 days and changes in performance ranking regarding mortality for a considerable proportion of hospitals, according to a study in the July 18 issue of JAMA.

“Increasing attention has been given to defining the quality and value of health care through reporting of process and outcome measures. National quality profiling efforts have begun to report hospital-level performance for Medicare beneficiaries, including 30-day mortality rates, for common medical conditions, including acute myocardial infarction [heart attack], heart failure, and community-acquired pneumonia,” according to background information in the article. Stroke is among the leading causes of death, disability, hospitalizations, and health care expenditures in the United States. “There is increasing interest in reporting risk-standardized outcomes for Medicare beneficiaries hospitalized with acute ischemic stroke, but whether it is necessary to include adjustment for initial stroke severity has not been well studied.”

Gregg C. Fonarow, M.D., of the University of California, Los Angeles, and colleagues conducted a study to evaluate the degree to which hospital outcome ratings and the ability to predict 30-day mortality are altered after including initial stroke severity in a claims-based risk model for hospital 30-day mortality for acute ischemic stroke. For the study, data were analyzed from 782 Get With The Guidelines-Stroke participating hospitals on 127,950 fee-for-service Medicare beneficiaries with ischemic stroke. The patients had a score documented for the National Institutes of Health Stroke Scale (NIHSS, a 15-item neurological examination scale with scores from 0 to 42, with higher scores indicating more severe stroke) between April 2003 and December 2009. The median (midpoint) age was 80 years, 57 percent were women, and 86 percent were white. Performance of claims-based hospital mortality risk models with and without inclusion of NIHSS scores for 30-day mortality was evaluated and hospital rankings from both models were compared. The NIHSS median score in this overall population was 5, and the median hospital-level NIHSS score was 5.

There were 18,186 deaths (14.5 percent) within the first 30 days, including 7,430 deaths during the index hospitalization (in-hospital mortality, 5.8 percent). The median hospital-level 30-day mortality rate was 14.5 percent. The researchers found that the hospital mortality model with NIHSS scores had significantly better discrimination than the model without. Also, other index scores demonstrated substantially more accurate classification of hospital 30-day mortality after the addition of NIHSS score to the claims model. The model with NIHSS exhibited better agreement between observed and predicted mortality rates.

Analysis of data indicated that more than 40 percent of hospitals identified in the top or bottom 5 percent of hospital risk-adjusted mortality would have been reclassified into the middle mortality range using a model adjusting for NIHSS score compared with a model without NIHSS score adjustment. “Similarly, when considering the top 20 percent and bottom 20 percent ranked hospitals, close to one-third of hospitals would have been reclassified,” the authors write.

“These findings highlight the importance of including a valid specific measure of stroke severity in hospital risk models for mortality after acute ischemic stroke for Medicare beneficiaries. Furthermore, this study suggests that inclusion of admission stroke severity may be essential for optimal ranking of hospital with respect to 30-day mortality.”

“As public reporting and value-based purchasing policies increase for outcome measures, it is important to recognize the effect that using models with less than ideal discrimination and calibration has on the ranking of hospitals and the lack of correlation among ranking by models that do and do not adjust for critical risk determinants,” the researchers write.

(JAMA. 2012;308[3]:257-264. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Comparing Hospitals on Stroke Care – The Need to Account for Stroke Severity

In an accompanying editorial, Tobias Kurth, M.D., Sc.D., of the University of Bordeaux, France, and Mitchell S. V. Elkind, M.D., M.S., of Columbia University, New York, write that the results of this study “clearly highlight the importance of incorporating information on stroke severity when conducting health outcomes research in stroke.”

“Excluding this information will lead to incorrect ranking of hospital performance by failing to consider that hospitals care for different patient populations. The influence of stroke severity on these outcome measures, moreover, seems different from that of measures of severity in other conditions. For other cardiovascular diseases, risk adjustment using demographic characteristics and claims-derived comorbid conditions may sufficiently account for the underlying case mix. Ischemic stroke is a much more heterogeneous condition than ischemic heart disease and is characterized by multiple subtypes, etiologies, and diverse outcomes. The assumption that what is true of myocardial infarction is also true of stroke, therefore, is flawed, as the present data underscore. The particular characteristics of stroke have to be taken into consideration by clinicians, insurance companies, and policy makers when comparing disease-specific health outcomes.”

(JAMA. 2012;308[3]:292-293. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 17, 2012

Media Advisory: To contact corresponding author Helen Tremlett, Ph.D., call Brian Lin at 604-822-6397 or email brian.lin@ubc.ca. To contact editorial co-author Ludwig Kappos, M.D., email lkappos@uhbs.ch
 

CHICAGO – Among patients with relapsing-remitting multiple sclerosis (MS), treatment with the widely-prescribed drug to treat MS, interferon beta, was not associated with less progression of disability, according to a study in the July 18 issue of JAMA.

“A key feature of MS is clinical progression of the disease over time manifested by the accumulation of disability. Interferon beta drugs are the most widely prescribed disease-modifying drugs approved by the U.S. Food and Drug Administration for the treatment of relapsing-onset MS, the most common MS disease course,” according to background information in the article. The authors add that there is a lack of well-controlled longitudinal studies investigating the effect of interferon beta on disability progression.

Afsaneh Shirani, M.D., of the University of British Columbia, Vancouver, Canada, and colleagues conducted a study to investigate the association between interferon beta exposure and disability progression in relapsing-remitting MS. The study included prospectively collected data (1985-2008) from British Columbia.  Patients with relapsing-remitting MS treated with interferon beta (n = 868) were compared with untreated contemporary (n = 829) and historical (prior to the approval of interferon beta) (n = 959) groups. The primary outcome measured was time from interferon beta treatment eligibility (baseline) to a confirmed and sustained score of 6 (requiring a cane to walk 100 meters; confirmed at >150 days with no measurable improvement) on the Expanded Disability Status Scale (EDSS) (range, 0-10, with higher scores indicating higher disability).

Follow-up time (first to last EDSS measurement) differed between groups, being considerably longer for the historical untreated cohort (median [midpoint], 10.8 years), who by definition entered the study much earlier than the contemporary cohorts. The median follow-up times for the contemporary cohorts were 5.1 years for the treated group and 4.0 years for the untreated group.

The observed outcome rates for reaching a sustained EDSS score of 6 were 10.8 percent in the treated group; 5.3 percent in the contemporary untreated group; and 23.1 percent in the historical untreated group.

“After adjustment for potential baseline confounders (sex, age, disease duration, and EDSS score), exposure to interferon beta was not associated with a statistically significant difference in the hazard of reaching an EDSS score of 6 when either the contemporary control cohort or the historical control cohort were considered,” the researchers write.  Further adjustment for co-existing illnesses and socioeconomic status, where possible, did not change interpretations.

“In conclusion, we did not find evidence that administration of interferon beta was associated with a reduction in disability progression in patients with relapsing-remitting MS. The ultimate goal of treatment for MS is to prevent or delay long-term disability. Our findings bring into question the routine use of interferon beta drugs to achieve this goal in MS. It is, however, possible that a subgroup of patients benefit from interferon beta treatment and that this association would not be discernable in our comprehensive ‘real-world’ study. Further work is needed to identify these potential patients; perhaps through pharmacogenomic or biomarker studies, paving the way for a tailored, personalized medicine approach. Our findings also encourage the investigation of novel therapeutics for MS.”

(JAMA. 2012;308[3]:247-256. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, July 17 at this link.

Editorial: Evaluating the Potential Benefit of Interferon Treatment in Multiple Sclerosis

Tobias Derfuss, M.D., and Ludwig Kappos, M.D., of University Hospital Basel, Switzerland, write in an accompanying editorial that the “rigorously collected data of Shirani and colleagues reinforce the conclusion that the associations between use of interferons and long-term disability, although plausible, remain unproven.

“As Shirani and colleagues suggest, more effective treatment options and better criteria that lead to more accurate selection of patients who might best respond to these treatments are needed. The relatively low progression rate in the untreated contemporary cohort is reassuring because it indicates that despite the unreliable explicit prognostic criteria, neurologists and patients in British Columbia seem to have made the right choices.”

(JAMA. 2012;308[3]:290-291. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Kappos’ and Dr. Derfuss’ institution receives drug company grants and/or payments for various activities including development of educational presentations, service on speakers bureaus, board memberships, and consultancies.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 10, 2012

The Moral Duty to Buy Health Insurance

Tina Rulli, Ph.D., of the NIH Clinical Center, Bethesda, Md., and colleagues write that one of the most controversial features of the 2010 Patient Protection and Affordable Care Act (ACA) is the requirement that U.S. residents purchase health insurance or pay a financial penalty.  The authors write that it should be a “duty to buy health insurance based on the moral duty individuals have to reduce certain burdens they pose on others.”

“Physicians and hospitals have a moral duty to provide acute care and emergency care to those who need it. The burdens of providing such care to the uninsured are very high, while the cost of purchasing insurance to cover these costs is not excessive for many. It follows that individuals have an enforceable moral duty to buy sufficient health insurance to cover the costs of acute care and emergency care.”

(JAMA. 2012;308[2]:137-138. Available pre-embargo to the media at http://media.jamanetwork.com)

Patient Satisfaction and Patient-Centered Care – Necessary but Not Equal

Joel M. Kupfer, M.D., of the Methodist Medical Center, Peoria, Ill., and Edward U. Bond, Ph.D., of Bradley University, Peoria, write that according to an Institute of Medicine report, patient-centeredness is defined as “providing care that is respectful of and representative to individual patient preferences, needs, and values and ensuring that patient values guide all clinical decisions.”

The authors examine the issues involved with patient care and satisfaction. “If patient satisfaction is accepted as a valid outcome, then it should be held to the same standard as any other intervention or device. Namely, does it objectively and efficiently improve health care outcomes? As of today, patient satisfaction surveys do not have that credibility as supported by the medical literature,” they write. “Patient satisfaction should be embraced as a desirable goal but it must undergo critical analysis.”

(JAMA. 2012;308[2]:139-140. Available pre-embargo to the media at http://media.jamanetwork.com)

Eliminating the Use of Partially Hydrogenated Oil in Food Production and Preparation

William H. Dietz, M.D., Ph.D., and Kelley S. Scanlon, Ph.D., R.D., of the Centers for Disease Control and Prevention, Atlanta, discuss the progress in reducing trans-fatty acid (TFA) intake in the United States and the potential health benefits of further reducing intake by eliminating a primary source of TFA, partially hydrogenated oils.

“Although the United States has made significant progress in reducing industrially produced TFA intake in the U.S. diet, industrially produced TFAs remain in the food supply and are consumed at higher levels by some population subgroups. Efforts to eliminate partially hydrogenated oils in all packaged foods and foods prepared and sold in restaurants and other food service outlets will help to ensure that consumers are no longer exposed to the industrially produced TFAs that can increase their risk of coronary heart disease.”

(JAMA. 2012;308[2]:143-144. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 10, 2012

Media Advisory: To contact John P. Neoptolemos, M.D., email J.P.Neoptolemos@liverpool.ac.uk.

CHICAGO – Patients who had surgery for periampullary cancer (a variety of types of cancer that are located in and near the head of the pancreas, including an area called the ampulla where the bile duct joins up with the pancreatic duct to empty their secretions into the upper small intestine) and received chemotherapy had a statistically significant survival benefit, compared to patients who did not receive chemotherapy, after adjusting for prognostic variables, according to a study in the July 11 issue of JAMA.

Periampullary carcinomas arise from the head of the pancreas. “The clinical presentation is similar to that of pancreatic ductal adenocarcinoma, and together they represent a major cause of death. Around 80 percent of periampullary adenocarcinomas are resectable and thus comprise around 30 percent to 40 percent of all resections for cancers in the head of the pancreas,” according to background information in the article. Although chemotherapy after surgery has been shown to have a survival benefit for pancreatic cancer, there have been no randomized trials for periampullary adenocarcinomas.

John P. Neoptolemos, M.D., of the University of Liverpool, England, and colleagues conducted a study to determine whether adjuvant chemotherapy (fluorouracil or gemcitabine) provides improved overall survival following resection. The randomized controlled trial (July 2000-May 2008) was conducted in 100 centers in Europe, Australia, Japan, and Canada. Of the 428 patients included in the primary analysis, 297 had ampullary, 96 had bile duct, and 35 had other cancers. One hundred forty-four patients were assigned to the observation group, 143 patients to receive folinic acid via intravenous bolus injection followed by fluorouracil via intravenous bolus injection administered 1 to 5 days every 28 days, and 141 patients to receive intravenous infusion of gemcitabine once a week for 3 of every 4 weeks for 6 months.

Two hundred forty-four patients (57 percent) had died at the time of analysis, 88 (61 percent) in the observation group, 83 (58 percent) in the fluorouracil plus folinic acid group, and 73 (52 percent) in the gemcitabine group. For the primary analysis, in the observation group, the median (midpoint) survival was 35.2 months and in the chemotherapy group 43.1 months.

The unadjusted primary analysis of the primary outcome of survival did not demonstrate a significant benefit for adjuvant chemotherapy. “Multivariate analysis, correcting for prognostic variables, found a statistically significant survival benefit to chemotherapy and specifically for gemcitabine compared with observation, notwithstanding the better safety profile compared with fluorouracil plus folinic acid, but these results should be considered hypothesis generating. There were different survival outcomes by tumor type, although age, poorly differentiated tumor grade, and lymph node involvement were also independent survival factors,” the authors write.

“Although this study found support for the use adjuvant chemotherapy to improve survival in patients with periampullary cancers, this effect was modest, indicating a need for further improvements and warranting the testing of combination chemotherapies.”

(JAMA. 2012;308[2]:147-156. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. Please see the article for additional information, including other authors, author contributions and affiliations, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 10, 2012

Media Advisory: To contact Philippe De Wals, M.D., Ph.D., call Sylvain Gagné at 418-656-3952 or email sylvain.gagne@dc.ulaval.ca.

Guillain-Barre syndrome (GBS) is usually characterized by rapidly developing motor weakness and areflexia (the absence of reflexes). “The disease is thought to be autoimmune and triggered by a stimulus of external origin. In 1976-1977, an unusually high rate of GBS was identified in the United States following the administration of inactivated ‘swine’ influenza A(H1N1) vaccines. In 2003, the Institute of Medicine (IOM) concluded that the evidence favored acceptance of a causal relationship between the 1976 swine influenza vaccines and GBS in adults. Studies of seasonal influenza vaccines administered in subsequent years have found small or no increased risk,” according to background information in the article. “In a more recent assessment of epidemiologic studies on seasonal influenza vaccines, experimental studies in animals, and case reports in humans, the IOM Committee to Review Adverse Effects of Vaccines concluded that the evidence was inadequate to accept or reject a causal relationship.”

Philippe De Wals, M.D., Ph.D., of Laval University, Quebec City, Canada and colleagues conducted a study to assess the risk of GBS following pandemic influenza vaccine administration. In fall 2009 in Quebec an immunization campaign was launched against the 2009 influenza A(H1N1) pandemic strain. By the end of the year, 4.4 million residents had been vaccinated. The study included follow-up over the 6-month period of October 2009 through March 2010 for suspected and confirmed GBS cases reported by physicians, mostly neurologists, during active surveillance or identified in the provincial hospital summary discharge database. Immunization status was verified.

Over the 6-month period, 83 confirmed GBS cases were identified. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. Analysis of data indicated a small but significant risk of GBS following influenza A(H1N1) vaccination. The number of cases attributable to vaccination was approximately 2 per 1 million doses. The excess risk was observed only in persons 50 years of age or older.

“In Quebec, the individual risk of hospitalization following a documented influenza A(H1N1) infection was 1 per 2,500 and the risk of death was 1/73,000. The H1N1 vaccine was very effective in preventing infections and complications. It is likely that the benefits of immunization outweigh the risks,” the authors write.

(JAMA. 2012;308[2]:175-181. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This study was funded by the Ministere de la Sante et des Services sociaux du Quebec and by the Public Health Agency of Canada-Canadian Institutes for Health Research Influenza Research Network. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 10, 2012

Media Advisory: To contact Mark F. Newman, M.D., call Sarah Avery at 919-660-1306 or email sarah.avery@duke.edu.

CHICAGO – Among intermediate- to high-risk patients undergoing coronary artery bypass graft surgery, administration of the agent acadesine to regulate adenosine (a naturally occurring chemical that dilates blood flow and can improve coronary blood flow and perfusion) did not reduce all-cause death, nonfatal stroke, or need for mechanical support for ventricular dysfunction, for approximately a month after surgery, according to a study in the July 11 issue of JAMA.

“Despite improvements in myocardial protection and perioperative care, the risk of death is still substantial in the first month after coronary artery bypass graft (CABG) surgery, averaging 3 percent to 6 percent, and can be even higher in patients with poor left ventricular function. Up to 50 percent of these deaths have been attributed to a cardiac cause, and this percentage has remained fairly constant over time,” according to background information in the article. “In a meta-analysis of randomized controlled trials, perioperative and postoperative infusion of acadesine, a first-in-class adenosine-regulating agent, was associated with a reduction in early cardiac death, myocardial infarction, and combined adverse cardiac outcomes in participants undergoing on-pump CABG surgery.” The authors add that the administration of adenosine during CABG surgery is difficult to regulate and led to the development of adenosine-regulating agents, of which acadesine is the first to be tested in large-scale clinical trials.

Mark F. Newman, M.D., of Duke University Medical Center, Durham, N.C., and colleagues conducted a study designed to more definitely test whether acadesine could reduce the composite of all-cause mortality, nonfatal stroke, or need for mechanical support for severe left ventricular dysfunction (SLVD) occurring during and after CABG surgery through postoperative day 28. The Reduction in Cardiovascular Events by Acadesine in Patients Undergoing CABG (RED-CABG) trial, a randomized, placebo-controlled study included intermediate- to high-risk patients (median [midpoint] age, 66 years) undergoing nonemergency, on-pump CABG surgery at 300 sites in 7 countries. The majority of participants were white men with a history of hyperlipidemia, diabetes, family history of cardiovascular disease, and previous percutaneous coronary intervention (procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries). Enrollment occurred from May 2009 to July 2010. Eligible participants were randomized to receive acadesine or placebo beginning just before anesthesia induction.

The trial was stopped after 3,080 of the originally projected 7,500 study participants were randomized because early analysis indicated a very low likelihood of a statistically significant efficacious outcome. The final sample size consisted of 2,986 patients in the intention to treat analysis. The researchers found that the primary efficacy outcome (composite of all-cause mortality, nonfatal stroke, or need for mechanical support for SLVD) was observed in 5 percent of participants overall. There was no significant difference between the placebo and acadesine groups, with incidence rates of 5.0 percent and 5.1 percent, respectively.

Additional exploratory efficacy end points, including length of mechanical ventilation, intensive care unit and hospital stay, and quality of life, did not reach statistical significance.

“These findings illustrate inherent risks of using promising meta-analysis results to plan ‘confirmatory’ clinical trials. There are several potential explanations for the negative results we observed. One consideration is the decision around study eligibility criteria and the overall primary end point of the trial,” the authors write. They add that the lack of benefit of acadesine may be related to the dosing regimen used.

The researchers conclude that the incidence of the primary composite end point of 5 percent indicates the need for continued investigation into therapies to reduce perioperative morbidity and mortality. “However, effective therapies remain elusive.”

(JAMA. 2012;308[2]:157-164. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The RED-CABG study was funded by Schering-Plough (subsequently Merck Sharp & Dohme Corp., Whitehouse Station, N.J.). Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 10, 2012

Media Advisory: To contact co-author Anders Hviid, M.Sc., Dr.Med.Sci., email aii@ssi.dk or call +45-32683967. To contact editorial co-author Mark C. Steinhoff, M.D., call Jim Feuer at 513-636-4656 or email jim.feuer@cchmc.org.

CHICAGO – In studies examining the risk of adverse outcomes after receipt of the influenza A(H1N1) vaccine, infants exposed to the vaccine in utero did not have a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction; while in another, study researchers found a small increased risk in adults of the nervous system disorder, Guillain-Barre syndrome, during the 4 to 8 weeks after vaccination, according to 2 studies in the July 11 issue of JAMA.

In the first study, Björn Pasternak, M.D., Ph.D., of the Statens Serum Institut, Copenhagen, Denmark and colleagues investigated whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of major birth defects, preterm birth, and fetal growth restriction. According to background information in the article, the 2009 influenza A(H1N1) pandemic put pregnant women at increased risk of illness, death, and poor pregnancy outcomes. “Pregnant women were among the main target groups prioritized for vaccination against influenza A(H1N1)pdm09, and an estimated 2.4 million women were vaccinated during pregnancy in the United States alone. However, assessment of the fetal safety of H1N1 vaccination in pregnancy has been limited to a few pharmacovigilance reports and descriptive cohort studies.”

The registry-based study included all live-born singleton infants in Denmark delivered between November 2, 2009, and September 30, 2010. The researchers estimated the prevalence odds ratios of adverse fetal outcomes, comparing infants exposed and unexposed to an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy. Following exclusions, a group of 53,432 live-born infants was identified with 6,989 (13.1 percent) exposed to the vaccine during pregnancy.

In a propensity score-matched analysis of 330 infants exposed to the vaccine in the first trimester of pregnancy and 330 unexposed, there were 18 infants (5.5 percent) diagnosed with a major birth defect among those exposed compared with 15 (4.5 percent) among the unexposed.  Among infants exposed to the H1N1 vaccine in the first trimester, 31 (9.4 percent) were born preterm compared with 24 (7.3 percent) among the unexposed. Preterm birth occurred in 302 of 6,543 infants (4.6 percent) with second- or third-trimester exposure, compared with 295 of 6,366 unexposed infants (4.6 percent). “Taking gestational age into account, there was no increased risk of small size for gestational age associated with vaccination in the first (25 [7.6 percent] exposed vs. 31 [9.4 percent] unexposed) or the second or third trimester (641 [9.7 percent] exposed vs. 657 [9.9 percent] unexposed),” the researchers write.

“In conclusion, this nationwide cohort study in Denmark found no significant associations between exposure to an AS03-adjuvanted influenza A(H1N1)pdm09 vaccine in pregnancy and risk of adverse fetal outcomes including major birth defects, preterm birth, and growth restriction. Although the data provide robust evidence of safety with respect to outcomes associated with second- or third-trimester exposure, results from analyses of first-trimester exposure should be viewed as preliminary and need confirmation. Further research also needs to address risk of specific birth defects as well as effectiveness of H1N1 vaccination in pregnancy.”

(JAMA. 2012;308[2]:165-174. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This work was funded by the Danish Medical Research Council. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, July 10 at this link.

Editorial: Influenza Pandemics—Pregnancy, Pathogenesis, and Perinatal Outcomes

In an accompanying editorial, Mark C. Steinhoff, M.D., of the Cincinnati Children’s Hospital Medical Center, and Noni E. MacDonald, M.D., M.Sc., F.R.C.P.C., of Dalhousie University, Halifax, Nova Scotia, Canada, write that “taken together, these studies partially assuage concerns about safety of adjuvanted pandemic influenza vaccines during pregnancy.”

“However, more studies are needed examining other types of vaccine adjuvants. In addition, observational studies of vaccines are limited by biases, including selection bias, as well as confounding by indication. Thus, future studies with improved statistical designs including prospective follow-up studies using virological end points with adjustments for selection, seasonality, and other biases are needed to confirm these data.”

(JAMA. 2012;308[2]:184-185. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 3, 2012

Media Advisory: To contact corresponding author Jeffrey R. Curtis, M.D., M.S., M.P.H., call Bob Shepard at 205-934-8934 or email Bshep@uab.edu.

CHICAGO – Although some have suggested that patients receiving medication for immune-mediated diseases such as rheumatoid arthritis or psoriasis may be at increased risk of herpes zoster (HZ; shingles) shortly after receipt of the vaccine, an analysis that included nearly 20,000 vaccinated Medicare beneficiaries finds that the live zoster vaccine is not associated with an increased risk of HZ shortly after vaccination in patients currently treated with biologics, and that it is associated with a significantly reduced longer-term risk of HZ in patients with an immune-mediated disease, according to a study in the July 4 issue of JAMA.

“A live attenuated vaccine reduces HZ risk by 70 percent and 51 percent among immunocompetent individuals 50 to 59 years and 60 years and older in 2 randomized blinded trials, respectively,” according to background information in the article. “The risk of HZ is elevated by 1.5 to 2 times in patients with rheumatic and immune-mediated diseases such as rheumatoid arthritis and Crohn’s disease. This increase has been attributed to both the underlying disease process and treatments for these conditions.” Currently, the Food and Drug Administration (FDA) and other organizations consider the live HZ vaccine to be contraindicated in patients receiving some immunosuppressive medications commonly used to treat these conditions, including all immune-modulating biologic agents and some nonbiologic immunosuppressive medications. The safety concern is that these individuals may develop varicella infection from the vaccine virus strain, the authors write.

Jie Zhang, Ph.D., of the University of Alabama at Birmingham, and colleagues, evaluated patients with immune-mediated diseases. The retrospective cohort study included 463,541 Medicare beneficiaries 60 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis (a form of chronic inflammation of the spine), or inflammatory bowel disease using Medicare claims data from January 2006 through December 2009. The researchers measured the incidence rate of herpes zoster within 42 days after vaccination (a safety concern) and beyond 42 days.

The average age of the patients at the start of follow-up was 74 years, with the median (midpoint) duration of follow-up being 2 years; 72 percent of the patients were women, and 86 percent were white. During the study, 18,683 patients (4.0 percent) received the zoster vaccine.

The researchers found that among 633 patients exposed to biologics, including 551 patients exposed to anti-tumor necrosis factor (TNF) biologics, no cases of varicella or HZ occurred within the 42 days following vaccination. Among all patients, only 1 case of primary varicella was identified within the 42-day risk window, occurring on day 10 after vaccination.

During the period of more than 42 days after vaccination, the researchers observed 138 HZ cases. After controlling for demographics, type of immune-mediated disease, health care utilization, and exposure to biologic and nonbiologic disease-modifying antirheumatic drugs (DMARDs) and oral glucocorticoids, data indicated that vaccination was associated with decreased HZ risk over a median of 2 years of follow-up.

“Despite the recognition that patients with immune-mediated conditions are at increased risk of HZ, this and previous studies have shown that only a small fraction of these patients received the vaccine, likely in part due to safety concerns. Our data call into question the current recommendations that HZ vaccine is contraindicated in patients receiving biologics and suggest a need for a randomized controlled trial to specifically address the safety and effectiveness of HZ vaccination among patients receiving biologics,” the authors conclude.

(JAMA. 2012;308[1]:43-49. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: This project was supported by the Agency for Healthcare Research and Quality (AHRQ). Dr. Zhang received support from the AHRQ, and Dr. Curtis received support from AHRQ and the National Institutes of Health. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 3, 2012

Projected Explosive Material, Not Blast Pressure, May Be Primary Cause of Eye Injuries From Fireworks

“Injuries from fireworks are prevalent among youth. The eye is the most frequently injured body part and accounts for more than 2,000 injuries annually. Although it is suggested that the pressure wave caused by explosions (i.e., blast overpressure) can cause eye injury (scleral bleeding and globe rupture), there is no clear evidence to support this,” writes Vanessa D. Alphonse, B.S., of Virginia Tech-Wake Forest University, Blacksburg, Va., and colleagues, who conducted a study to assess the mechanisms involved in eye injuries caused by fireworks.

As reported in a Research Letter, human cadaver eyes were procured from the North Carolina Eye Bank. Due to the variability of consumer fireworks, 10 gram charges of gunpowder were used to simulate fireworks in a controlled, repeatable manner. Eyes were pressurized to physiological human intraocular pressure before testing. A total of 18 open field blast tests were conducted at varying distances from the cornea. The researchers found that minor grain-sized corneal abrasions were the only injuries observed. The abrasion size and pattern suggested unspent explosive material was projected onto the eye, which was confirmed with high-speed video. The firework blast overpressures did not cause serious eye injuries. “This study provides information about injury mechanisms of fireworks that could aid in public policy decisions regarding firework laws and in the design of protective equipment.”

(JAMA. 2012;308[1]:33-34. Available pre-embargo to the media at http://media.jamanetwork.com)

Viewpoints in This Week’s JAMA

‘The Battered-Child Syndrome’ 50 Years Later – Much Accomplished, Much Left to Do

“A half century ago, Kempe and colleagues published in JAMA ‘The Battered-Child Syndrome,’ an article that would change the way physicians and others care for children with injuries. Although this article was not the first in the medical literature to address the problem of physical abuse of children, the authors did report the first epidemiologic study and highlighted important aspects of the evaluation of suspected abuse …,” writes John M. Leventhal, M.D., of the Yale School of Medicine, New Haven, Conn., and Richard D. Krugman, M.D., of the University of Colorado School of Medicine, Aurora.

The authors write that the 50th anniversary of this article is an opportunity to reflect on 3 salient lessons learned over the past 5 decades about the care of maltreated children: (1) many children and families are affected; (2) the consequences can be lifelong and intergenerational; and (3) treatment and prevention can work but need to be expanded.

(JAMA. 2012;308[1]:35-36. Available pre-embargo to the media at http://media.jamanetwork.com)

Child Abuse Reporting – Rethinking Child Protection

Susan C. Kim, J.D., M.P.H., of the Georgetown University Law Center, Washington, D.C., and colleagues examine the issue of what is the duty to report suspected cases of child abuse by individuals in positions of trust over young people, such as in the church or university sports.

“Religious institutions, colleges, and schools have close ties to their communities, and the integrity of their employees is a matter of upmost public concern. These institutions should adopt stringent child protection policies because many sexual predators, often familiar with state law, seek out relationships with children in which they can assume positions of responsibility for the children. Institutions have a responsibility to be vigilant in preventing and detecting child abuse by members of their community.”

(JAMA. 2012;308[1]:37-38. Available pre-embargo to the media at http://media.jamanetwork.com)

Ensuring Appropriate Expert Testimony for Cases Involving the ‘Shaken Baby’

Daniel M. Albert, M.D., M.S., of the University of Wisconsin School of Medicine and Public Health, Madison (and Editor, Archives of Ophthalmology), and colleagues offer suggestions on how improve the quality of expert medical testimony given at trials of suspected pediatric abusive head trauma (AHT) (“shaken baby” syndrome).

“… it is essential that a system is in place to provide some degree of certainty that physicians testifying for both the prosecution and defense as AHT medical experts are indeed expert, experienced, and unbiased,” they write. Additionally, they suggest “a certification program should be developed for medical professionals called on to provide opinions of diagnoses in cases of suspected AHT, thus providing them the prerequisite training, experience, and knowledge of the literature regarding AHT to be considered qualified to give expert testimony on this topic.”

(JAMA. 2012;308[1]:39-40. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 3, 2012

Media Advisory: To contact corresponding author Clinton K. Murray, M.D., call Jen Rodriguez at 210-916-5141 or email jen.d.rodriguez@us.army.mil.

CHICAGO – In analysis that included more than 9 million Department of Defense nonactive and active duty personnel, the rates of both community-onset and hospital-onset methicillin-resistant Staphylococcus aureus (MRSA) bacteremia decreased from 2005 to 2010, while the proportion of community-onset skin and soft tissue infections due to MRSA has more recently declined, according to a study in the July 4 issue of JAMA.

“The magnitude of invasive MRSA infections as well as the emergence of community-onset MRSA infections in the United States has been well documented,” according to background information in the article. “In parallel with the emergence of community-onset MRSA infections in the U.S. civilian population, skin and soft tissue infections (SSTIs) have become a significant public health issue for the U.S. military. … Rates of hospital-onset MRSA infections are reported as decreasing, but recent rates of community-onset S aureus infections are less known.”

Michael L. Landrum, M.D., of the San Antonio Military Medical Center, Fort Sam Houston, Texas, and colleagues conducted a study to examine the incidence rates of community-onset and hospital-onset S aureus bacteremia and SSTIs and the proportion due to MRSA in a large population composed of individuals of all ages from all regions of the United States. The analysis consisted of an observational study of all Department of Defense TRICARE beneficiaries from January 2005 through December 2010. Medical record databases were used to identify and classify all annual first-positive S aureus blood and wound or abscess cultures as methicillin-susceptible S aureus (MSSA) or MRSA, and as community-onset or hospital-onset infections (isolates collected >3 days after hospital admission).

From 2005 through 2010, there were more than 9.2 million people eligible to receive care within the Department of Defense health care system each year. In the first year of observation (2005), 52 percent of individuals in the study population were men and 84 percent were nonactive duty. There were 2,643 blood and 80,281 wound or abscess annual first-positive S aureus cultures included in the study for further analyses. Community-onset infections accounted for 2,094 (79 percent) cases of S aureus bacteremia and 79,801 (99 percent) cases of S aureus SSTIs. The rate of community-onset MRSA bacteremia was highest for those aged 65 years or older. The rates of community-onset bacteremia were higher in men than in women. Fifty-eight percent of community-onset S aureus SSTIs were due to MRSA, significantly higher than for either community-onset bacteremia (39 percent) or hospital-onset SSTIs (53 percent). Fifty-four percent of cases of hospital-onset bacteremia were due to MRSA.

The researchers found that the annual incidence rates for community-onset and hospital-onset MRSA bacteremia decreased from 2005 to 2010. “Concurrently, the proportion of community-onset SSTI due to MRSA peaked at 62 percent in 2006 before decreasing annually to 52 percent in 2010.”

The authors highlight several findings from this study, including that the rates of hospital-onset MRSA bacteremia significantly decreased and that rates of both community-onset and hospital-onset MRSA bacteremia decreased in parallel. The annual rates of community-onset MSSA bacteremia also decreased significantly. “However, the proportions of both community-onset and hospital-onset S aureus bacteremia due to MRSA did not change significantly, suggesting balanced decreases in the rates of both MRSA and MSSA bacteremia. For community-onset MRSA SSTIs, no significant overall trend in annual rates was observed, but the proportion of community-onset SSTIs due to MRSA declined significantly.” They add that within the U.S. Military Health System, the burden of S aureus bacteremia and SSTIs remains substantial, highlighting the importance of having successful prevention and treatment strategies.

“These observations, taken together with results from others showing decreases in the rates of health care-associated infections from MRSA, suggest that broad shifts in the epidemiology of S aureus infections may be occurring. Additional studies are needed to assess whether these trends will continue, which prevention methods are most effective, and to what degree other factors may be contributing.”

(JAMA. 2012;308[1]:50-59. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Please Note: For this study, there will be multimedia content available, including the JAMA Report video, embedded and downloadable video, audio files, text, documents, and related links. This content will be available at 3 p.m. CT Tuesday, July 3 at this link.

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EMBARGOED FOR RELEASE: 3 P.M. (CT), MONDAY, JULY 2, 2012

Media Advisory: For more information, contact JAMA Network Media Relations at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

CHICAGO –  The nine specialty Archives Journals in the JAMA Network will change their names effective Jan. 1, 2013, part of the ongoing evolution to more closely interconnect the scientific journals published by the American Medical Association.

The journals will be renamed JAMA Dermatology, JAMA Facial Plastic Surgery, JAMA Internal Medicine, JAMA Neurology, JAMA Ophthalmology, JAMA Otolaryngology-Head & Neck Surgery, JAMA Pediatrics, JAMA Psychiatry and JAMA Surgery.

The name changes will coincide with the first major print redesign of JAMA Network journals in 20 years.

“While we all realize that changes in the names of our journals, which have been revered for decades, may raise some concerns among our loyal readers and authors, we believe that standardization of format and integration into The JAMA Network will justify these changes in the long run,” JAMA editor in chief Howard Bauchner M.D., and the nine specialty journal editors write in an editorial formally announcing the name changes.

The covers of the renamed journals will continue to reference their former Archives titles for several months following the January change.

Two of the specialty journals will see their new names shortened: the Archives of Pediatrics & Adolescent Medicine will become JAMA Pediatrics and the Archives of General Psychiatry will be known as JAMA Psychiatry.

“Today, adolescent medicine is an established discipline within the broader field of pediatrics, and the evolution of our name from American Journal of Diseases of Children to Archives of Pediatrics & Adolescent Medicine to JAMA Pediatrics reflects this broadening of the bailiwick of the field, the deepening of the knowledge and expertise of its members, and our commitment to all who care for and about individuals in this age group. Although ‘adolescent medicine’ will no longer be in our name, clinical care of adolescents and advancing the science of adolescent medicine remain a central part of who we are as a journal,” journal editor Frederick P. Rivara, M.D., M.P.H., writes along with some of the journal’s leadership in an editorial.

The JAMA Network also has recently unveiled a new website and a smartphone/tablet app will be available soon.

“What will the future bring for The JAMA Network Journals? We will continue to publish the best content – including original research reports, practical review articles and scholarly opinion pieces. Our goal is not to be print-centric or web-centric, but rather to be user-centric, regardless of who those users are – authors, researchers, clinicians, educators, policy makers, librarians, journalists, and, in some cases, patients,” Bauchner’s editorial notes.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 26, 2012

 
Bone Density Screening Intervals for Osteoporosis – One Size Does Not Fit All

Elaine W. Yu, M.D., and Joel S. Finkelstein, M.D., of Massachusetts General Hospital, Boston, write that Medicare data indicate that over a 7-year period, only 52 percent of eligible women had a bone density test, and that half of U.S. postmenopausal women older than 50 years will experience an osteoporotic fracture in their lifetime. “… the controversial issue of how to determine bone density screening intervals has contributed to confusion about bone density testing. Rates of bone loss calculated from repeat bone density tests are an independent predictor of fragility fracture but the optimal intervals for rescreening are unclear, primarily due to a relative absence of data on this topic.”

The authors discuss the use of bone density rescreening; how screening intervals should be determined; and provide suggestions on appropriate screening intervals.

(JAMA. 2012;307[24]:2591-2592. Available pre-embargo to the media at http://media.jamanetwork.com)

Health Information Technology in the Era of Care Delivery Reform – To What End?

Asaf Bitton, M.D., M.P.H., of Brigham and Women’s Hospital, Boston, and colleagues write that during the past decade, the United States has moved from whether to digitally wire the U.S. health care system to when to do it. “Health information technology is inevitable. The question now is how best to do it.”

“New models of more effective care must be identified, whether accountable care organizations, patient-centered medical homes, or some yet-undiscovered entity, and the needs of clinical teams and patients must be understood and met to succeed. That is the function. The forms of electronic health records should follow. Electronic health records should not be electronic versions of the paper record, simply enhanced for billing for a fee-for-service delivery model. These systems have the potential to transform health care delivery, but only if they are designed with a new end in mind: more integrated, safer care that engages patients and reduces costs.”

(JAMA. 2012;307[24]:2593-2594. Available pre-embargo to the media at http://media.jamanetwork.com)

Assessing Individual Physician Performance – Does Measurement Suppress Motivation?

Christine K. Cassel, M.D., of the American Board of Internal Medicine, Philadelphia, and Sachin H. Jain, M.D., M.B.A., of Brigham and Women’s Hospital, Boston, write that the current system of health care has invested a great deal in measures to assess physician performance, both financially and intellectually, and the goals they seek to achieve are critical to a high-functioning health care system.

“To reach sustainable quality goals, however, close attention must be given to whether and how these initiatives motivate physicians and not turn physicians into pawns working only toward specific measurable outcomes, losing the complex problem-solving and diagnostic capabilities essential to their role in quality of patient care, and diminish their sense of professional responsibility by making it a market commodity. Rewards should reinforce, not undermine, intrinsic motivation to pursue needed improvement in health system quality.”

(JAMA. 2012;307[24]:2595-2596. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the articles for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JUNE 26, 2012

Media Advisory: To contact corresponding author Eric D. Peterson, M.D., M.P.H., call Debbe Geiger at 919-660-9461 or email Debbe.Geiger@duke.edu. To contact editorial author Mark J. Alberts, M.D., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu.

CHICAGO – The use of intravenous tissue plasminogen activator (tPA) among warfarin-treated patients (with an INR 1.7 or less) who had an acute ischemic stroke was not associated with increased risk of symptomatic intracranial hemorrhage, compared with the use of intravenous tPA among non-warfarin-treated patients in routine clinical practice, according to a study in the June 27 issue of JAMA.

“Intravenous tissue plasminogen activator is currently the only effective treatment to improve outcomes for acute ischemic stroke; however, treatment with intravenous tPA carries the risk of symptomatic intracranial hemorrhage (sICH). Of patients who receive intravenous tPA for stroke, 2.4 percent to 8.8 percent experience this potentially life-threatening complication,” according to background information in the article. “Although current guidelines endorse administering intravenous tPA to warfarin-treated patients if their international normalized ratio (INR) is 1.7 or lower, there are few data on safety of intravenous tPA in warfarin-treated patients in clinical practice.” Without safety data some investigators have expressed concern regarding administration of intravenous tPA to warfarin-treated patients with stroke.

Ying Xian, M.D., Ph.D., of the Duke Clinical Research Institute, Durham, N.C., and colleagues evaluated the association between warfarin treatment and sICH among patients with stroke receiving intravenous tPA in routine clinical practice. The study (with data from the American Heart Association Get With The Guidelines-Stroke Registry), included 23,437 patients with ischemic stroke and with INR of 1.7 or lower, treated with intravenous tPA in hospitals from April 2009 through June 2011.

Among the patients in the study receiving intravenous tPA, 1,802 (7.7 percent) were taking warfarin prior to admission. Warfarin-treated patients were older; more likely to be women; had more comorbid conditions, and had more severe strokes. The baseline INR levels were higher in warfarin-treated patients (median [midpoint], 1.20 vs. 1.00). Overall, 1,107 patients (4.7 percent) developed sICH after intravenous tPA administration. Warfarin-treated patients had a higher overall unadjusted rate of sICH than did non-warfarin-treated patients (5.7 percent vs. 4.6 percent). However, after risk adjustment, warfarin use was not an independent predictor of sICH risk.

“The rates of life-threatening or serious systemic hemorrhage were similar in both groups (0.9 percent vs. 0.9 percent), although higher unadjusted rates of any tPA complication (10.6 percent vs. 8.4 percent) and mortality (11.4 percent vs. 7.9 percent) were observed in warfarin-treated patients. However, after multivariable adjustment, warfarin use was not associated with life-threatening or serious systemic hemorrhage, any tPA complication, or in-hospital mortality,” the authors write.

The researchers also found that among warfarin-treated patients with INRs of 1.7 or lower, the degree of anticoagulation was not statistically significantly associated with sICH risk.

The authors note that they “found the potential for substantial undertreatment, because up to 50 percent of warfarin-treated patients who might have been eligible for reperfusion therapy did not receive intravenous tPA. These data provide empirical support of current American Heart Association/American Stroke Association guideline recommendations and may help support future stroke quality improvement efforts.”

(JAMA. 2012;307[24]:2600-2608. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Editorial: Cerebral Hemorrhage, Warfarin, and Intravenous tPA – The Real Risk Is Not Treating

Mark J. Alberts, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, writes in an accompanying editorial that “considering that intravenous tPA remains substantially underutilized in the United States for patients with stroke, with few if any alternate therapies, medical professionals should ensure that eligible patients receive this important therapy.”

“The study by Xian et al is a positive step in that direction, providing evidence that patients taking warfarin and with INRs of 1.7 or lower can be treated without experiencing a significantly increased risk of sICH. The real risk is in not treating otherwise eligible patients, who may then have prolonged morbidity from their stroke. To paraphrase some surgical colleagues, ‘A chance to treat is a chance to cure.’ The results of the current study provide another chance to treat a serious and potentially disabling disease that has very few effective medical therapies.”

(JAMA. 2012;307[24]:2637-2638. Available pre-embargo to the media at http://media.jamanetwork.com)

Editor’s Note: The author has completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and reported serving as a consultant for Genentech, Boehringer Ingelheim, Janssen, and The Joint Commission and serving as a speaker for, and receiving honoraria for preparation of educational materials from, Genentech and Boehringer Ingelheim.

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