EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 27, 2013

Reduction Seen in Rates of Gastroenteritis Hospitalizations in Older Children and Adults Since Implementation of Infant Rotavirus Vaccination

“Implementation of infant rotavirus vaccination in 2006 has substantially reduced the burden of severe gastroenteritis among U.S. children younger than 5 years,” write Paul A. Gastanaduy, M.D., M.P.H., of the Centers for Disease Control and Prevention, Atlanta, and colleagues. “Whether indirect protection (due to reduced transmission of rotavirus) extends to adults remains unclear.”

As reported in a Research Letter, the authors assessed patterns of gastroenteritis hospitalizations among children 5 years of age or older and among adults before and after implementation of infant rotavirus immunization. Rotavirus-coded and cause-unspecified gastroenteritis discharges from January 2000 through December 2010 were retrieved from a nationally representative database of hospital inpatient stays, the Nationwide Inpatient Sample.  Estimates were determined of annual and monthly incidence rate ratios (RR) of the postvaccine years (2008, 2009, and 2010) separately and combined vs. the prevaccine years (2000-2006); 2007 was a transition year with limited coverage and was excluded.

The researchers found that compared with prevaccine years, during 2008-2010, statistically significant reductions were observed in rotavirus-coded discharges in the age groups 0-4 years; 5-14 years; and 15-24 years. Similarly, significant reductions were observed in cause-unspecified discharges in the age groups 0-4 years; 5-14 years; 15-24 years; and 25-44 years. “Compared with prevaccine years, significant reductions in rotavirus-coded discharges occurred up to age 25 years in 2008, age 15 years in 2009, and across all age groups in 2010, with similar patterns for cause-unspecified discharges. Cause-unspecified reductions across all age groups and postvaccine years were focused in the late winter and early spring; in 2010, significant reductions were observed in March or April for all age groups.”

“The pattern of observed reductions in gastroenteritis discharges among unvaccinated older children and adults is consistent with indirect protection resulting from infant rotavirus vaccination,” the authors write. “These results point to the primacy of children in the transmission of rotavirus and illustrate how indirect benefits may amplify the effect of the U.S. rotavirus vaccination program.”

(doi: 10.1001/jama.2013.170800; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Paul A. Gastanaduy, M.D., M.P.H., call Jeanette St. Pierre at 404-639-3648  or email zcr5@cdc.gov.

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Viewpoint Appearing in This Issue of JAMA

Revealing the Incidentalome When Targeting the Tumor Genome

“… the process of decoding the genome of a patient’s tumor may incidentally reveal information about inherited predispositions to cancer and other diseases (the ‘incidentalome’). There is a need to establish approaches to decision making with respect to the return of these incidental results,” write Yvonne Bombard, Ph.D., of the Memorial Sloan-Kettering Cancer Center, New York, and colleagues.

“Optimal interpretation of the cancer genome requires a comparison with the inherited genome, but it is possible to avoid explicit listing of inherited variants. This strategy is justifiable in retrospective genomic research, but is less supportable in the prospective setting. For prospective research and clinical translation, the path forward depends on approaches that better define actionable variants and the development of the evidence base and clinical infrastructure to support preference-based disclosure of incidental findings. This will require the creation and evaluation of decision tools and the clinical capacity to provide genomic counseling for which no standards of care exist. Understanding how patients and clinicians interpret, manage, and use the genomic information they receive is essential to measure health service outcomes, risk-benefit trade-offs, and overall cost-effectiveness.”

(JAMA. 2013;310(8):795-796; Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Kenneth Offit, M.D., M.P.H., call Courtney Nowak at 646-227-3633 or email denicolc@mskcc.org.

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

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 27, 2013

Media Advisory: To contact corresponding author Taylor S. Riall, M.D., Ph.D., call Raul Reyes at 409-747-0794 or email rareyes@utmb.edu. To contact editorial co-author Karl Y. Bilimoria, M.D., M.S., call Marla Paul at 312-503-8928 or email marla-paul@northwestern.edu.

CHICAGO – In an analysis of a procedure used to help prevent common duct injury during gallbladder removal surgery, use of intraoperative cholangiography (radiologic examination of the ducts during gallbladder surgery) was not associated with a reduced risk of common duct injury, according to a study in the August 28 issue of JAMA.

“Biliary anatomy misidentification during cholecystectomy [gallbladder removal] can result in injury to the common hepatic duct or common bile duct. Common duct injuries cause significant short- and long-term morbidity including major operations, multiple hospitalizations, and biliary strictures. Elimination of common duct injury is desirable, but it has remained stubbornly present with rates ranging from 0.3 percent to 0.5 percent,” according to background information in the article. “When routinely used, intra­operative cholangiography is thought to prevent common duct injury. However, controversy exists regarding the effectiveness of routine use in the prevention of common duct injury.”

Kristin M. Sheffield, Ph.D., and Taylor S. Riall, M.D., Ph.D., of the University of Texas Medical Branch, Galveston, and colleagues investigated the association between intraoperative cholangiography use during cholecystectomy and common duct injury, using instrumental variable analysis, an effective way to overcome unmeasured confounding (i.e., factors influencing outcomes not found in the database). The researchers identified Medicare beneficiaries from Texas Medicare claims data who underwent inpatient or outpatient cholecystectomy for conditions including biliary colic or biliary dyskinesia, acute cholecystitis, or chronic cholecystitis. Percentage of intraoperative cholangiography use at the hospital and by surgeon were the instrumental variables. Patients with claims for common duct repair operations within 1 year of cholecystectomy were considered as having major common duct injury.

A total of 92,932 Medicare beneficiaries 66 years or older underwent cholecystectomy at 307 hospitals in Texas from 2001 through 2009. There were 37,533 cholecystectomies with intraoperative cholangiography (40.4 percent) and 55,399 without (59.6 percent). Common duct injury occurred in 280 patients (0.30 percent). There were 201 common duct injuries (0.36 percent) in patients undergoing cholecystectomy without intraoperative cholangiography and 79 injuries (0.21 percent) for those having an intraoperative cholangiography.

“In a logistic regression model controlling for patient, surgeon, and hospital characteristics, the odds of common duct injury for cholecystectomies performed without intraoperative cholangiography were increased compared with those performed with it. When confounding was controlled with instrumental variable analysis, the association between cholecystectomy performed without intraoperative cholangiography and duct injury was no longer significant,” the authors write.

“Significant controversy exists regarding the role of intraoperative cholangiography in the prevention of common duct injury during cholecystectomy. Previous population-based studies using data from Medicare claims, hospital discharge records, and national inpatient registries report nearly 2-fold higher rates of injury in cholecystectomies performed without intraoperative cholangiography. In the present study using Texas Medicare claims data, the association between intraoperative cholangiography and common duct injury was highly sensitive to the analytic method used.”

“Failure to account for potentially confounding variables not routinely captured in administrative databases has a major effect on the interpretation of the findings. Intraoperative cholangiography was not associated with significant reduction in common duct injury using instrumental variable analysis. Instrumental variable analysis balances unmeasured confounding variables to better align risk factors in comparator groups. With better control for unmeasured confounding variables, intraoperative cholangiography was no longer associated with common duct injury. Based on these results, routine intraoperative cholangiography should not be advocated as means for preventing common duct injury,” the researchers conclude.

(JAMA. 2013;310(8):812-820; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study is supported by grants from the National Institutes of Health. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Kuo reports a pending grant with the Agency for Healthcare Research and Quality. No other disclosures were reported.

Editorial: Laparoscopic Cholecystectomy, Intraoperative Cholangiograms, and Common Duct Injuries

In an accompanying editorial, Karl Y. Bilimoria, M.D., M.S., of the Feinberg School of Medicine, Northwestern University, Chicago, and colleagues comment on the findings of this study.

“While the report by Sheffield et al does not definitively close the door on routine intraoperative cholangiography use, the authors have again directed attention to an important clinical debate by using a new approach to revisit the outcomes of intraoperative cholangiography using observational data. While the true effect of intraoperative cholangiography on the safety of laparoscopic cholecystectomy remains controversial, this study will undoubtedly reinvigorate the discussion.”

(JAMA. 2013;310(8):801-802; Available pre-embargo to the media at https://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, AUGUST 27, 2013

Media Advisory: To contact J. Michael McWilliams, M.D., Ph.D., call David Cameron at 617-432-0441 or email david_cameron@hms.harvard.edu.

CHICAGO – Payment incentives implemented with a commercial accountable care organization (ACO) initiative in Massachusetts –Blue Cross Blue Shield’s Alternative Quality Contract (AQC) – were associated with lower spending for Medicare enrollees served by the provider groups participating in the AQC, findings that suggest that evaluations of ACO programs may need to consider the implications for other patient populations to assess their full clinical and economic benefits, according to a study in the August 28 issue of JAMA.

“In response to mounting pressures to deliver more cost-effective care, provider organizations have exhibited increasing willingness to assume financial risk for the quality and costs of the care they provide. More than 250 provider groups have contracted with Medicare as ACOs, and many similar payment arrangements have been reached with commercial insurers by these and other groups,” according to background information in the article. “In a multipayer system, new payment incentives implemented by one insurer for an ACO may also affect spending and quality of care for another insurer’s enrollees served by the ACO. Such spillover effects reflect the extent of organizational efforts to reform care delivery and can contribute to the net impact of ACOs.”

J. Michael McWilliams, M.D., Ph.D., of Harvard Medical School, Boston, and colleagues conducted a study to examine whether the Blue Cross Blue Shield (BCBS) of Massachusetts’ Alternative Quality Contract (AQC), an early commercial ACO initiative associated with reduced spending and improved quality for BCBS enrollees, was also associated with changes in spending and quality for Medicare beneficiaries, who were not covered by the AQC. The study included comparisons from 2007-2010 of elderly fee-for-service Medicare beneficiaries in Massachusetts served by 11 provider organizations entering the AQC in 2009 or 2010 (intervention group) vs. beneficiaries served by other providers (control group). The researchers estimated changes in spending and quality for the intervention group in the first and second years of exposure to the AQC relative to concurrent changes for the control group. The primary outcome was total quarterly medical spending per beneficiary. Secondary outcomes included spending by setting and type of service, 5 process measures of quality, potentially avoidable hospitalizations, and 30-day readmissions.

The researchers found that differential changes in sociodemographic and clinical characteristics were small for the intervention group relative to the control group, and none was statistically significant, suggesting that the findings were not due to changes in patient case mix. Adjusted total quarterly spending was $150 higher for the intervention group than for the control group, and spending trends were similar before AQC incentives were implemented for participating organizations. “In year 2 of the intervention group’s exposure to the AQC, the spending difference between the intervention and control groups was reduced to $51, constituting a significant differential change of -$99 or a 3.4 percent savings relative to an expected quarterly mean of $2,895. Savings in year 1 were not statistically significant.”

Savings in year 2 were explained largely by differential changes in outpatient care (-$73) and included significant differential changes in spending on office visits, emergency department visits, minor procedures, imaging, and laboratory tests. Estimated savings in year 2 spending on outpatient care for the intervention group were greater among beneficiaries with 5 or more conditions (-$125) than among those with fewer conditions (-$61).

“Annual rates of low-density lipoprotein cholesterol testing differentially improved for beneficiaries with diabetes in the intervention group by 3.1 percentage points and for those with cardiovascular disease by 2.5 percentage points, but performance on other quality measures did not differentially change,” the authors write.

“Our findings have several implications for payment and delivery system reforms. In general, cost-reducing spillover effects of ACO contracts with one insurer on care for other insurers’ enrollees should signal a willingness among provider organizations generating the spillovers to enter similar contracts with additional insurers; they could be rewarded for the savings and quality improvements achieved for the other insurers’ enrollees. Broad organizational responses to early ACO initiatives, like those suggested by our findings, might support a rapid transition among ACOs to global payment arrangements with multiple payers. Conversely, cost-reducing spillovers present a free-riding problem to commercial insurers engaged in ACO contracts, since competing insurers with similar provider networks could offer lower premiums without incurring the costs of managing an ACO. Additional efforts to foster multipayer participation in global payment sys­tems, such as recent state initiatives and provisions in Pioneer Medicare ACO contracts, may be important.”

“… our study suggests that organizations in Massachusetts willing to assume greater financial risk were capable of achieving modest reductions in spending for Medicare beneficiaries without compromising quality of care. Although effects of commercial and Medicare ACO initiatives similar to the AQC may differ in other markets, these findings suggest potential for these payment models to foster systemic change in care delivery. Evaluations of ACO programs may need to consider spillover effects on other patient populations to assess their full clinical and economic benefits,” the researchers conclude.

(JAMA. 2013;310(8):829-836; Available pre-embargo to the media at https://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, AUGUST 27, 2013

Media Advisory: To contact corresponding author Lu Qi, M.D., Ph.D., call Todd Datz at 617-432-8413 or email tdatz@hsph.harvard.edu; to contact corresponding author Alessandro Doria, M.D., Ph.D., M.P.H., call Jeff Bright at 617-309-1957 or email Jeffrey.bright@joslin.harvard.edu.

CHICAGO – Researchers have identified a previously unknown genetic locus (the place a gene occupies on a chromosome) significantly associated with increased coronary heart disease risk among patients with type 2 diabetes, but the association was not found in individuals without diabetes, according to a study in the August 28 issue of JAMA. The variant is functionally related to glutamic acid metabolism, suggesting a mechanistic link.

“The prevalence of type 2 diabetes has been steadily increasing in the United States and other countries, with the total number of affected people reaching more than 370 million globally. Long-term cardiovascular complications, and especially coronary heart disease (CHD), are the principal causes of morbidity and mortality among diabetic patients,” according to background information in the article. “Diabetes is associated with an elevated risk of CHD. Previous studies have suggested that the genetic factors predisposing to excess cardiovascular risk may be different in diabetic and nondiabetic individuals.”

Lu Qi, M.D., Ph.D., of the Harvard School of Public Health, Boston, and colleagues conducted a study to identify genetic determinants of CHD that are specific to patients with diabetes. The researchers studied 5 independent sets of CHD cases and CHD-negative controls from the Nurses’ Health Study (enrolled in 1976 and followed up through 2008), Health Professionals Follow-up Study (enrolled in 1986 and followed up through 2008), Joslin Heart Study (enrolled in 2001-2008), Gargano Heart Study (enrolled in 2001-2008), and Catanzaro Study (enrolled in 2004-2010). Included were a total of 1,517 CHD cases and 2,671 CHD-negative controls, all with type 2 diabetes. Results in patients with diabetes were compared with those in 737 nondiabetic CHD cases and 1,637 nondiabetic CHD-negative controls from the Nurses’ Health Study and Health Professionals Follow-up Study cohorts.

Of the 2,543,016 genetic variants that were tested for association with CHD in stage 1 of the 3-stage genome-wide analysis, 26 met the criterion for promotion to stage 2, and 3 of these further met the criterion for promotion to stage 3. Of the 3 variants that were promoted to stage 3, a variant on chromosome 1q25 (rs10911021) was consistently associated with CHD risk among diabetic participants. No association between this variant and CHD was detected among nondiabetic participants.

“The locus is in the region of the GLUL gene on chromosome 1q25 and may affect CHD risk by reducing the expression of this gene and affecting glutamate and glutamine metabolism in endothelial cells. This genetic variant appeared to be specifically associated with CHD in the diabetic population and showed a significant gene-by-diabetes synergism on CHD risk,” the authors write. “… further studies are needed to fully understand the biological mechanisms linking it to CHD in diabetes.”

(JAMA. 2013;310(8):821-828; Available pre-embargo to the media at https://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, AUGUST 27, 2013

Media Advisory: To contact corresponding author Shyamasundaran Kottilil, M.D., Ph.D., call Anne Oplinger at 301-402-1663 or email AOplinger@niaid.nih.gov.

CHICAGO – Treatment of chronic hepatitis C virus (HCV) genotype 1 infection with the interferon-free regimen of sofosbuvir and ribavirin resulted in a high sustained virologic response rate in a patient population with unfavorable treatment characteristics, according to a study in the August 28 issue of JAMA.

“Chronic infection with hepatitis C virus is a major cause of chronic liver disease, end-stage liver disease, hepatocellular cancer and remains the leading indication for liver transplants in western countries. The HCV epidemic in the United States is centered in large urban areas among populations with a high prevalence of unfavorable traditional predictors of treatment response,” according to background information in the article. “Recent studies show that interferon-free, directly acting antiviral agent-only regimens can successfully achieve sustained virologic response (SVR); however, populations traditionally associated with poorer treatment outcomes have been underrepresented.”

Anuoluwapo Osinusi, M.D., M.P.H., of the National Institutes of Health, Bethesda, Md., and colleagues evaluated the efficacy of sofosbuvir administered in combination with weight-based or low-dose once daily ribavirin in a treatment-naive population with unfavorable characteristics of treatment success. The randomized, 2-part, phase 2 study included 60 patients with HCV genotype 1 enrolled from October 2011-April 2012. In the study’s first part, 10 participants with early to moderate liver fibrosis were treated with 400 mg/d of sofosbuvir and weight-based ribavirin for 24 weeks. In the second part, 50 participants with all stages of liver fibrosis were randomized 1:1 to receive 400 mg of sofosbuvir with either weight-based or low-dose 600 mg/d of ribavirin for 24 weeks. The primary outcome was the proportion of participants with undetectable HCV viral load 24 weeks after treatment completion (sustained virologic response of 24 weeks [SVR₂₄]). Eighty-three percent of the participants were black; 66 percent, men; and 23 percent had advanced liver disease.

Twenty-four participants (96 percent) in each group achieved viral suppression by week 4. “A total of 7 participants (28 percent) in the weight-based group and 10 (40 percent) in the low-dose group relapsed after treatment completion leading to SVR₂₄ rates of 68 percent in the weight-based group and 48 percent in the low-dose group,” the authors write.

The combination regimen was safe and well tolerated with no death or discontinuation of treatment due to adverse events. The most frequent adverse events were headache, anemia, fatigue, and nausea, the severity of which ranged from mild to moderate.

The researchers also found that the baseline factors of male sex, advanced liver disease, and high baseline HCV RNA levels were associated with relapse.

“This study demonstrates the efficacy of an interferon-free regimen in a traditionally difficult-to-treat population while exploring the reasons for treatment relapse. In this study, treatment of chronic HCV infection with a single directly acting antiviral agent (sofosbuvir) and weight-based ribavirin resulted in a high SVR rate in a population with unfavorable traditional predictors of treatment response compared with reported rates with currently used interferon-based therapy in similar populations.”

(JAMA. 2013;310(8):804-811; Available pre-embargo to the media at https://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, AUGUST 20, 2013

Study Shows Gypsum Wallboard Does Not Keep Out Carbon Monoxide, Questioning CO Detector Exemptions For Certain Types of Residences

“Carbon monoxide (CO) poisoning is a significant U.S. health problem, responsible for approximately 500 accidental deaths annually, and a risk of 18 percent to 35 percent for cognitive brain injury 1 year after poisoning. Most morbidity and mortality from CO poisoning is believed to be preventable through public education and CO alarm use. States have been enacting legislation mandating residential CO alarm installation. However, as of December 2012, 10 of the 25 states with statutes mandating CO alarms exempted homes without fuel-burning appliances or attached garages, believing that without an internal CO source, risk is eliminated. This may not be true if CO diffuses directly through wall-board material,” write Neil B. Hampson, M.D., of Virginia Mason Medical Center, Seattle, and colleagues.

As reported in a Research Letter, a Plexiglas chamber divided by various configurations of gypsum wallboard was used to determine whether CO diffuses across drywall. Wallboard of various thickness levels were tested. Carbon monoxide test gas was infused into the chamber and then CO concentrations were measured once per minute in each chamber for 24 hours. The authors sought to determine how rapidly a concentration of CO toxic to humans would be reached in the noninfused chamber and whether diffusion would then continue.

The researchers found that carbon monoxide diffused across single-layer gypsum wallboard of 2 thicknesses, double-layer wallboard, and painted double-layer wallboard. “Gypsum’s permeability to CO is due to its porosity. … The ability of CO to diffuse across gypsum wallboard may explain at least some instances of CO poisoning in contiguous residences. Exempting residences without internal CO sources from the legislation mandating CO alarms may put people in multifamily dwellings at risk for unintentional CO poisoning.”

(JAMA. 2013;310[7]:745-746. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Neil B. Hampson, M.D., call Gale Robinette at 206-341-1509 or email gale.robinette@vmmc.org.

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 Viewpoints Appearing in This Issue of JAMA

 A Call for an End to the Diet Debates

“As the obesity epidemic persists, the time has come to end the pursuit of the ‘ideal’ diet for weight loss and disease prevention. The dietary debate in the scientific community and reported in the media about the optimal macronutrient-focused weight loss diet sheds little light on the treatment of obesity and may mislead the public regarding proper weight management. Numerous randomized trials comparing diets differing in macronutrient compositions (e.g. low-carbohydrate, low-fat, Mediterranean) have demonstrated differences in weight loss and metabolic risk factors that are small and inconsistent,” write Sherry L. Pagoto, Ph.D., of the University of Massachusetts Medical School, Worcester, and Bradley M. Appelhans, Ph.D., of Rush University Medical Center, Chicago.

“Because behavioral adherence is much more important than diet composition, the best approach is to counsel patients to choose a dietary plan they find easiest to adhere to in the long term. Patients should develop an appropriate physical activity program and learn behavioral modification to promote long-term adherence. Although research specifically focused on improving adherence is ongoing, the number of studies being conducted is small compared with head-to-head macronutrient-focused diet comparison studies. Advancing obesity treatment requires emphasis on the biological, behavioral, and environmental factors influencing adherence to lifestyle changes and developing reimbursement strategies to support lifestyle interventions.”

(JAMA. 2013;310[7]:687-688. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Sherry L. Pagoto, Ph.D., call Lisa Larson at 508-856-2689 or email LisaM.Larson@umassmed.edu.

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Early Detection and Intervention in Schizophrenia – A New Therapeutic Model

Jeffrey A. Lieberman, M.D., of the New York State Psychiatric Institute, New York, and colleagues write that “a new conceptualization of schizophrenia has led to a new care model developed for patients with first-episode schizophrenia that fosters recovery and prevents disability.”

“The elements of this care model for proactive treatment of early psychosis include (1) reducing the duration of active symptoms through rapid diagnosis and treatment of patients with first-episode psychosis (ensuring adherence to the pharmacologic regimen is critical); (2) sustaining treatment and preventing psychotic relapse following the acute treatment response in the context of maintenance medication or supported discontinuation; (3) integrating pharmacologic management with psychosocial therapies and recovery-oriented approaches that involve other mental health professionals in the context of a disease-management approach to the illness; and (4) offering social and vocational services, substance abuse treatment, family education and support, and assistance with coping with past trauma and the trauma of psychosis, as well as suicide prevention and safety planning.”

(JAMA. 2013;310[7]:689-690. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Jeffrey A. Lieberman, M.D., call Rachel Yarmolinsky at 212-543-5353 or email Yarmoli@nyspi.columbia.edu.

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 Perspectives on Complementary and Alternative Medicine Research

In this Viewpoint, Josephine P. Briggs, M.D., and Jack Killen, M.D., of the National Center for Complementary and Alternative Medicine, National Institutes of Health (NIH), Bethesda, Md., describe the 2013 NIH perspective on investment in research on complementary and alternative medicine interventions and call for a more nuanced conversation about them.

“First and foremost, the conversation should reflect current realities, including the evolution of research priorities and the shifts in funding to projects that address them rather than areas that have less scientific promise or less amenability to scientific investigation. Second, although discussions about complementary and alternative medicine often imply a clear demarcation distinguishing a monolithic alternative domain from conventional medicine, this distinction breaks down in the realities of the pluralistic U.S. health care system. The boundaries also shift—in both directions as evidence changes. Third, the conversation should recognize the state of current evidence indicating that some of these practices are useful and can appropriately be integrated into care, some should not, some are dangerous and merit regulatory attention, and many are somewhere in between.”

(JAMA. 2013;310[7]:691-692. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Josephine P. Briggs, M.D., call Katy Danielson at 301-496-7790 or email nccampress@mail.nih.gov.

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

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 20, 2013

Media Advisory: To contact Bjarke Feenstra, Ph.D., email fee@ssi.dk.

CHICAGO – Researchers have identified a new genome-wide significant locus (the place a gene occupies on a chromosome) for infantile hypertrophic pyloric stenosis (IHPS), a serious gastrointestinal condition associated with gastrointestinal obstruction, according to a study in the August 21 issue of JAMA. Characteristics of this locus also suggest the possibility of an inverse relationship between levels of circulating cholesterol in neonates and IHPS risk.

“Infantile hypertrophic pyloric stenosis is the leading cause of gastrointestinal obstruction in the first months of life, with an incidence of l to 3 per 1,000 live births in Western countries. It affects 4 to 5 times as many boys as girls and typically presents 2 to 8 weeks after birth with projectile vomiting, weight loss, and dehydration. Although IHPS is a clinically well-defined entity, the etiology [cause] of the condition is complex and remains unclear,” according to background information in the article. A genetic predisposition is well established; IHPS aggregates strongly in families and has an estimated heritability of more than 80 percent; but knowledge about specific genetic risk variants is limited.

Bjarke Feenstra, Ph.D., of the Statens Serum Institut, Copenhagen, Denmark, and colleagues conducted a study to search the genome for genetic associations with IHPS and to validate findings in 3 independent sample sets. During stage 1, the researchers used reference data from the 1,000 Genomes Project for imputation into a genome-wide data set of 1,001 Danish surgery-confirmed samples (cases diagnosed 1987-2008) and 2,371 disease-free controls. In stage 2, the 5 most significantly associated loci were tested in independent case-control sample sets from Denmark (cases diagnosed 1983-2010), Sweden (cases diagnosed 1958-2011), and the United States (cases diagnosed 1998-2005), with a total of 1,663 cases and 2,315 controls.

The researchers found a new genome-wide significant locus for IHPS at chromosome 11q23.3 in a region harboring the apolipoprotein (APOA1/C3/A4/A5) gene cluster. APOA1 encodes apolipoprotein A-I, which is the major protein component of high-density lipoprotein (HDL) cholesterol in plasma. “The functional characteristics of the 11q23.3 locus suggest the hypothesis that low levels of circulating lipids in newborns are associated with increased risk of IHPS. We addressed this hypothesis by measuring plasma levels of total, low-density lipoprotein, and HDL cholesterol as well as triglycerides in prospectively collected umbilical cord blood from a set of 46 IHPS cases and 189 controls of Danish ancestry, most of which were also in the discovery sample,” the authors write. They found lower cholesterol levels at birth in infants who went on to develop IHPS compared with matched controls who did not develop the disease.

“Further investigation is required to illuminate the functional significance of the association identified here.”

(JAMA. 2013;310(7):714-721; Available pre-embargo to the media at https://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, AUGUST 20, 2013

Media Advisory: To contact Orlando M. Gutierrez, M.D., M.M.Sc., call Tyler Greer at 205-934-2041 or email tgreer@uab.edu. To contact editorial co-author Wolfgang C. Winkelmayer, M.D., Sc.D., call Tracie White at 650-723-7628 or email traciew@stanford.edu.

CHICAGO – In a large national study, higher levels of the urinary albumin-to-creatinine ratio was associated with greater risk of incident but not recurrent coronary heart disease in black individuals when compared with white individuals, according to a study in the August 21 issue of JAMA.

“Increased urinary albumin excretion is an important marker of kidney injury and a strong risk factor for cardiovascular disease. Black individuals have higher levels of urinary albumin excretion than white individuals, which may contribute to racial disparities in cardiovascular outcomes,” according to background information in the study. Previous research indicated that the association of urinary albumin-to-creatinine ratio (ACR) with incident stroke differed by race, such that higher urinary ACR was independently associated with a greater risk of incident stroke in black individuals but not in white individuals. Whether similar associations extend to coronary heart disease (CHD) is unclear.

Orlando M. Gutierrez, M.D., M.M.Sc., of the University of Alabama at Birmingham, and colleagues conducted a study to determine whether the association of urinary albumin excretion with CHD events differs by race. The study included black and white U.S. adults, 45 years and older, who were enrolled within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 with follow-up through December 2009. The researchers examined race-stratified associations of urinary ACR in 2 groups: (1) incident CHD among 23,273 participants free of CHD at baseline; and (2) first recurrent CHD event among 4,934 participants with CHD at baseline.

Over a median (midpoint) 4.5 years of follow-up, a total of 616 incident CHD events (259 among black participants and 357 among white participants) were observed. Of these, 421 were nonfatal heart attacks and 195 were CHD-related deaths. Analysis of the data indicated that age- and sex-adjusted incidence rates increased in the higher categories of urinary ACR in both black and white participants. The adjusted incidence rates in the 2 highest categories of ACR were approximately 1.5-fold greater in black participants when compared with white participants.

“In models adjusted for traditional cardiovascular risk factors and medications, higher baseline urinary ACR was associated with greater risk of incident CHD among black participants but not white participants,” the authors write. “Among those with CHD at baseline, fully adjusted associations of baseline urinary ACR with first recurrent CHD event were similar between black participants vs. white participants.”

“These findings confirm the results of prior studies showing that urinary ACR is an important biomarker for CHD risk in the general population, even among individuals with ACR values that are less than the current threshold for defining microalbuminuria.  Additionally, to our knowledge, this is the first study to demonstrate that the higher risk of incident CHD associated with excess ACR differs by race.”

“Future studies should examine whether addition of ACR can improve the diagnosis and management of CHD in black individuals,” the researchers conclude.

(JAMA. 2013;310(7):706-713; Available pre-embargo to the media at https://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: Kidney Disease and Cardiovascular Risk – Whether Black or White Race Matters

Daniel E. Weiner, M.D., M.S., of Tufts Medical Center, Boston, and Wolfgang C. Winkelmayer, M.D., Sc.D., of the Stanford University School of Medicine, Palo Alto, Calif., (and Associate Editor, JAMA), write in an accompanying editorial the “the study by Gutierrez and colleagues reinforces that even mild elevations in urine ACR are associated with increased CVD risk, even though this level of albuminuria will have no meaningful systemic effects.”

“Differentiating between low normal and high normal urinary ACR may further aid in cardiovascular risk stratification, particularly in black individuals, and motivate prevention and heightened monitoring of these individuals.”

(JAMA. 2013;310(7):697-698; Available pre-embargo to the media at https://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, AUGUST 20, 2013

Media Advisory: To contact Matthew J. Parkes, B.Sc., email matthew.parkes@manchester.ac.uk

CHICAGO – Although a pooling of data from 12 studies showed a statistically significant association between use of lateral wedge insoles and lower pain in medial knee osteoarthritis, among trials comparing wedge insoles with neutral insoles, there was no significant or clinically important association between use of wedge insoles and reduction in knee pain, according to a study in the August 21 issue of JAMA.

“Osteoarthritis of the knee is a common painful chronic disease whose prevalence is increasing and for which there are few efficacious treatment options. The increase in rates of knee replacement for osteoarthritis has made the identification of effective nonsurgical treatments a high priority. Medial osteoarthritis is one of the most common subtypes of knee osteoarthritis. One type of treatment for medial knee osteoarthritis involves reducing medial (inner) loading to ease the physical stress applied to that compartment of the joint. The wedge is placed under the sole of the foot and angulated so that it is thicker over the lateral than the medial edge, transferring loading during weight bearing from the medial to the lateral knee compartment,” according to background information in the study.  However, studies examining knee pain following treatment have shown inconsistent findings.

Matthew J. Parkes, B.Sc., of the University of Manchester, England, and colleagues conducted a meta-analysis to assess the efficacy of lateral wedge treatments (shoes and insoles designed to reduce medial knee compartment loading) in reducing knee pain in patients with medial knee osteoarthritis. The authors conducted a search of the medical literature to identify randomized trials that compared shoe-based treatments (lateral heel wedge insoles or shoes with variable stiffness soles) aimed at reducing medial knee load, with a neutral or no wedge control condition. The wedge needed to be of 5° to 15° of angulation, which is a level shown in previous studies to reduce external knee adduction moment (torque). Studies must have included patient-reported pain as an outcome. Twelve trials met inclusion criteria with a total of 885 participants of whom 502 received lateral wedge treatment.

The researchers found, when considering all 12 trials, the overall effect estimate was a standard mean difference in pain between interventions that showed a moderately significant effect of a lateral wedge on pain reduction. However, the findings were highly heterogeneous across studies. Larger trials with a lower risk of bias suggested a null association.

When trials were grouped according to the control group treatment, the authors found that compared with neutral inserts, lateral wedges had no association with knee pain and heterogeneity was much lower across trial findings.

“These results suggest that compared with control interventions, lateral wedges are not efficacious for the treatment of knee pain in persons with medial knee osteoarthritis.”

(JAMA. 2013;310(7):722-730; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This review was funded by a special strategic award grant from Arthritis Research UK. Drs. LaValley and Felson are supported by a grant from the U.S. 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, AUGUST 20, 2013

Media Advisory: To contact Marc G. Jaffe, M.D., call Ann Marie Wallace at 510-390-3355 or email ann.m.wallace@kp.org; or call Joe Fragola at 415-902-3737 or email joe.c.fragola@kp.org. To contact editorial co-author Abhinav Goyal, M.D., M.H.S., call Jennifer Johnson McEwen at 404-727-5696 or email jrjohn9@emory.edu.

CHICAGO – Implementation of a large-scale hypertension program that included evidence-based guidelines and development and sharing of performance metrics was associated with a near-doubling of hypertension control between 2001 and 2009, compared to only modest improvements in state and national control rates, according to a study in the August 21 issue of JAMA.

“Hypertension affects 65 million adults in the United States (29 percent) and is a major contributor to cardiovascular disease. Although effective therapies have been available for more than 50 years, fewer than half of Americans with hypertension had controlled blood pressure in 2001-2002. Many quality improvement strategies for control of hypertension exist, but to date, no successful, large-scale program sustained over a long period has been described,” according to background information in the article.

Marc G. Jaffe, M.D., of the Kaiser Permanente South San Francisco Medical Center, South San Francisco, Calif., and colleagues conducted a study to examine the results of a hypertension program in Northern California and to compare rates of hypertension control in that program with statewide and national estimates. The Kaiser Permanente Northern California (KPNC) hypertension program included a multifaceted approach to blood pressure control. Key elements of the program include establishment of a comprehensive hypertension registry, development and sharing of performance metrics, evidence-based guidelines, medical assistant visits for blood pressure measurement, and single-pill combination pharmacotherapy. Patients identified as having hypertension within an integrated health care delivery system in Northern California from 2001-2009 were included.

The comparison group comprised insured patients in California between 2006-2009 who were included in the Healthcare Effectiveness Data and Information Set (HEDIS) commercial measurement by California health insurance plans participating in the National Committee for Quality Assurance (NCQA) quality measure reporting process. A secondary comparison group was included to obtain the reported national average NCQA HEDIS commercial rates of hypertension control between 2001-2009 from health plans that participated in the NCQA HEDIS quality measure reporting process.

Between 2001 and 2009, the KPNC hypertension registry increased from 349,937 to 652,763. Among hypertension registry members, the average age was 63 years. More than half of registry members were women, and the proportion was similar across study years.

The researchers found that the NCQA HEDIS commercial hypertension control rate within KPNC increased after implementation of the hypertension program from 43.6 percent in 2001 to 80.4 percent in 2009. “In contrast, the national mean NCQA HEDIS control rate increased from 55.4 percent to 64.1 percent between 2001 and 2009. California-wide control rates were available since 2006 and were similar but slightly higher than the national average (63.4 percent vs. 69.4 percent from 2006 to 2009),” the authors write.

Following the study period, the NCQA HEDIS hypertension control rate within KPNC continued to improve, from 83.7 percent in 2010 to 87.1 percent in 2011.

The authors also found that the rate of lisinopril-hydrochlorothiazide single-pill combination (SPC) prescriptions in KPNC increased from 13 to 23,144 prescriptions per month from 2001 to 2009. During this period, the percentage of angiotensin-converting enzyme (ACE) inhibitor prescriptions dispensed as an SPC (in combination with a thiazide diuretic) increased from less than 1 percent to 27.2 percent

“In summary, implementation of a large-scale hypertension program was associated with improvements in hypertension control rates between 2001 and 2009,” the researchers conclude.

(JAMA. 2013;310(7):699-705; Available pre-embargo to the media at https://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.

There will also be a digital news release available for this study, 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 20 at this link.

Editorial: Health System-Wide Quality Programs to Improve Blood Pressure Control

In an accompanying editorial, Abhinav Goyal, M.D., M.H.S., and William A. Bornstein, M.D., Ph.D., of the Emory School of Medicine, Atlanta, comment on the findings of this study.

“The transition to value-based models in all sectors of U.S. health care and the looming growth of accountable care organizations and shared savings models provides a framework wherein health care organizations have the flexibility to implement care models optimized to deliver the best outcomes at the lowest cost, without being constrained to face-to-face physician encounters to drive reimbursement. In this context, studies such as the one by Jaffe et al on the science of health system-level quality improvement are particularly powerful and hopefully will prompt hypertension guidelines and perhaps other guidelines to include recommendations about system-level approaches to managing risk factors.”

(JAMA. 2013;310(7):695-696; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Bornstein reported serving on an advisory panel for CIGNA. Dr. Goyal reported no disclosures.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 13, 2013

Study Examines Incidence of Sports-Related Sudden Death in France

“Although screening programs prior to participation in sports have been used for many years for young competitive athletes, it has been suggested that screening programs might also be worthwhile in the general population. Description of the incidence of sports-related sudden death by specific sports as well as by sex and age may help inform the debate,” write Eloi Marijon, M.D., of the Université Paris Descartes, Sorbonne Paris Cité, Paris, and colleagues.

As reported in a Research Letter, the study was performed in France between 2005 and 2010, and overall, 60 of 96 administrative districts participated voluntarily, and included a population of approximately 35 million inhabitants. Sports-related sudden death was reported by local emergency medical services and defined as death occurring during or within 1 hour of cessation of sports activity, whether the resuscitation was successful or not. Calculation of incidence of sports-related sudden death only included cases during moderate and vigorous exertion, and was assessed by sex, age range, as well as by the 3 most frequent sports among women in France (cycling, jogging, and swimming).

There were 775 sports-related sudden death cases during moderate to vigorous exertion over 5 years. Of these cases, 42 (5 percent) were women. “The average age of sudden death in women was 44 years vs. 46 years in men. The overall average incidence rate in women was estimated to be 0.51 per million female sports participants vs. 10.1 in men. The incidence rate of sports-related sudden death significantly increased with age among men, but not among women. The overall incidence of sudden death differed by sport for men but not women,” the authors write.

“Compared with men, we found a lower incidence of sports-related sudden death in women and differences by age and sport. … Strategies for community screening prior to participation in recreational sports activities should consider both the types of sports to be undertaken and the sex of participants. The incidence of sports-related sudden death is probably underestimated in this study.”

(JAMA. 2013;310[6]:642-643. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Eloi Marijon, M.D., email eloi_marijon@yahoo.fr.

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Viewpoints Appearing in This Issue of JAMA

The Evolution of the Master Diagnostician

In this Viewpoint, Gurpreet Dhaliwal, M.D., of the University of California, San Francisco, and Allan S. Detsky, M.D., Ph.D., of the University of Toronto, examine the “characterizations of the master diagnostician of the past, present, and future and considers the ways in which medical care has, is, and will be structured to help physicians develop and optimize this fundamental skill.”

“Although the clinical environment has changed tremendously in the past 50 years, the way the mind reasons and learns has not. The challenge has always been to structure training and work environments that care for patients but to also tend to the lifelong learning of the clinicians. In different eras, physicians have gotten the different parts of that puzzle right. Medical educators, administrators, and policy makers should take the best of the past and present to structure future training and practice that makes the master diagnostician the norm rather than the exception.”

(JAMA. 2013;310[6]:579-580. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Allan S. Detsky, M.D., Ph.D., call Suniya Kukaswadia at 416-978-7752 or email suniya.kukaswadia@utoronto.ca.

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 Social Media and Physicians’ Online Identity Crisis

“Physicians are increasingly counted among Facebook’s 1 billion users and Twitter’s 500 million members. Beyond these social media platforms, other innovative social media tools are being used in medical practice, including for online consultation, in the conduct of clinical research, and in medical school curricula,” write Matthew DeCamp, M.D., Ph.D., of Johns Hopkins University, Baltimore, and colleagues.

Institutions, medical boards, and physician organizations worldwide have promulgated recommendations for physician use of social media. A common theme among these recommendations is that physicians should manage patient-physician boundaries online by separating their professional and personal identities. “In this Viewpoint, we contend that this is operationally impossible, lacking in agreement among active physician social media users, inconsistent with the concept of professional identity, and potentially harmful to physicians and patients. A simpler approach that avoids these pitfalls asks physicians not whether potential social media content is personal or professional but whether it is appropriate for a public space.”

(JAMA. 2013;310[6]:581-582. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Matthew DeCamp, M.D., Ph.D., call Leah Ramsay at 202-642-9640 or email Lramsay@jhu.edu.

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

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 13, 2013

Media Advisory: To contact Rakesh M. Suri, M.D., D.Phil., call Traci Klein at 507-284-5005 or email Klein.traci@mayo.edu. To contact editorial author Catherine M. Otto, M.D., call Leila Gray at 206-685-0381 or email leilag@uw.edu.

CHICAGO – In a study that included patients with mitral valve regurgitation due to a condition known as flail mitral valve leaflets, performance of early surgical correction compared with initial medical management was associated with greater long-term survival and lower risk of heart failure, according to a study in the August 14 issue of JAMA.

“Degenerative mitral regurgitation [backflow of blood from the left ventricle to the left atrium due to mitral valve insufficiency] is common and can be surgically repaired in the vast majority of patients, improving symptoms and restoring normal life expectancy. Despite the safety and efficacy of contemporary surgical correction, an ongoing international debate persists regarding the need for early intervention in patients without American College of Cardiology (ACC)/American Heart Association (AHA) guideline class I triggers (no or minimal symptoms and absence of left ventricular dysfunction). This is in part propagated by discordant views of the prognostic consequences of uncorrected severe mitral regurgitation; considered as benign by those supporting medical watchful waiting (nonsurgical observation until a distinct event is encountered) vs. conveying excess mortality and morbidity (including heart failure and atrial fibrillation) by those advocating early surgical intervention,” according to background information in the article.

To understand the comparative effectiveness of early surgery vs. initial medical management strategies, Rakesh M. Suri, M.D., D.Phil., of the Mayo Clinic College of Medicine, Rochester, Minn., and colleagues conducted a study to ascertain the comparative effectiveness of initial medical management (nonsurgical observation) vs. early mitral valve surgery following the diagnosis of mitral regurgitation due to flail leaflets (an abnormality of the mitral valve in which a portion of the valve has lost its normal support). For the study, the researchers used data from the Mitral Regurgitation International Database (MIDA) registry, which includes 2,097 patients with flail mitral valve regurgitation (1980-2004) receiving routine cardiac care from 6 tertiary centers (France, Italy, Belgium, and the United States). Of 1,021 patients with mitral regurgitation without ACC and AHA guideline class I triggers, 575 patients were initially medically managed and 446 underwent mitral valve surgery within 3 months following detection.

Within 3 months following diagnosis, 8 patients died, 5 (1.1 percent) after early surgery vs. 3 (0.5 percent) during initial medical management; 9 patients developed heart failure, 4 (0.9 percent) after early surgery vs. 5 (0.9 percent) during initial medical management; and 30 patients developed new-onset atrial fibrillation, 6.2 percent after early surgery vs. 1.2 percent during initial medical management.

Ninety-eight percent of patients were followed up from diagnosis until death or at least 5 years. A total of 319 deaths were observed during an average follow-up time of 10.3 years. “Survival among the entire unmatched cohort for early surgery was 95 percent at 5 years, 86 percent at 10 years, 63 percent at 20 years vs. 84 percent at 5 years, 69 percent at 10 years, and 41 percent at 20 years for initial medical management, favoring early surgery,” the authors write. Early surgical correction of mitral valve regurgitation was associated with a 5-year reduction in mortality of 53 percent.

With class II triggers (atrial fibrillation or pulmonary hypertension), survival was again better with early surgery, both overall and in the matched cohort at 10 years.

During follow-up, 167 patients incurred at least 1 incident episode of heart failure representing a rate of 16 percent at 10 years and 27 percent at 20 years. In the overall cohort, heart failure was less frequent after early surgery (7 percent for early surgery vs. 23 percent for initial medical management at 10 years and 10 percent for early surgery vs. 35 percent for initial medical management at 20 years), with a heart failure risk reduction of approximately 60 percent.

Reduction in late-onset atrial fibrillation was not observed.

“These findings emanate from institutions that together provide a very high rate of mitral valve repair (>90 percent) with low operative mortality, emphasizing that such results might also be achieved in routine practice at many advanced repair centers,” the authors write. “The advantages associated with early surgical correction of mitral valve regurgitation were confirmed in both unmatched and matched populations, using multiple statistical methods.”

(JAMA. 2013;310(6):609-616; Available pre-embargo to the media at https://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: Surgery for Mitral Regurgitation – Sooner or Later?

In an accompanying editorial, Catherine M. Otto, M.D., of the University of Washington School of Medicine, Seattle, comments on how the findings of this study may influence patient care.

“The study group is atypical compared with most patients with chronic severe mitral regurgitation seen in clinical practice who are referred for surgical intervention at symptom onset or when serial imaging shows early left ventricular (LV) dysfunction. In patients with severe mitral regurgitation due to mitral valve prolapse, early surgery is reasonable if surgical risk is low and the likelihood of successful valve repair is high, which is often the case for patients with a flail leaflet; the new data support this recommendation.”

“However, if surgical risk is high or if the likelihood of valve repair is low, it remains uncertain whether early surgical intervention is appropriate in the asymptomatic patient with severe mitral regurgitation due to a flail leaflet when LV size and systolic function are normal. Although the majority of these patients will develop clear indications for valve surgery within 2 years, it may be reasonable to postpone the risks of having an intervention and having a prosthetic valve as long as possible.”

(JAMA. 2013;310(6):587-588; Available pre-embargo to the media at https://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 13, 2013

Media Advisory: To contact Pamela N. Peterson, M.D., M.S.P.H., call Jenny Bertrand at 303-520-9591 or email Jennifer.bertrand@dhha.org.

CHICAGO – In a large population of Medicare beneficiaries with heart failure who underwent implantation of a cardiac resynchronization therapy defibrillator, patients who had the cardiac characteristics of left bundle-branch block and longer QRS duration had the lowest risks of death and all-cause, cardiovascular, and heart failure readmission, according to a study in the August 14 issue of JAMA.

“Clinical trials have shown that cardiac resynchronization therapy (CRT) improves symptoms and reduces mortality and readmission among selected patients with heart failure and left ventricular systolic dysfunction. Following broad implementation of CRT, it was recognized that one-third to one-half of patients receiving the therapy for heart failure do not improve. Identification of patients likely to benefit from CRT is particularly important, because CRT defibrillator (CRT-D) implantation is expensive, invasive, and associated with important procedural risks. A primary question regarding optimal patient selection for CRT is whether patients with longer QRS duration or left bundle-branch block (LBBB) morphology derive greater benefit than others,” according to background information in the article. QRS duration is a measurement of the electrical conducting time of the heart on an electrocardiogram. Left bundle-branch block is a cardiac conduction abnormality.

Pamela N. Peterson, M.D., M.S.P.H., of Denver Health Medical Center, Denver, and colleagues conducted a study to determine the long-term outcomes of patients undergoing CRT-D implantation and associations between combinations of QRS duration and presence of LBBB and outcomes, including all-cause mortality; all-cause, cardiovascular, and heart failure readmission; and complications. The study included Medicare beneficiaries in the National Cardiovascular Data Registry’s ICD Registry between 2006 and 2009 who underwent CRT-D implantation. Patients were stratified according to whether they were admitted for CRT-D implantation or for another reason, then categorized as having either LBBB or no LBBB and QRS duration of either 150 ms or greater or 120 to 149 ms. Patients underwent follow-up for up to 3 years, through December 2011.

Mortality rates in the primary overall study cohort were 0.8 percent at 30 days, 9.2 percent at 1 year, and 25.9 percent at 3 years. Rates of all-cause readmission were 10.2 percent at 30 days and 43.3 percent at 1 year. The researchers found that after adjustment for demographic and clinical factors, compared with patients with LBBB and QRS duration of 150 ms or greater, the other 3 groups had significantly higher risks of mortality and all-cause, cardiovascular, and heart failure readmission. The adjusted risk of 3-year mortality was lowest among patients with LBBB and QRS duration of 150 ms or greater (20.9 percent), compared with LBBB and QRS duration of 120 to 149 ms (26.5 percent), no LBBB and QRS duration of 150 ms or greater (30.7 percent), and no LBBB and QRS duration of 120 to 149 ms (32.3 percent). The adjusted risk of l-year all-cause readmission were also lowest among patients with LBBB and QRS duration of 150 ms or greater (38.6 percent), compared with LBBB and QRS duration of 120 to 149 ms (44.8 percent), no LBBB and QRS duration of 150 ms or greater (45.7 percent), and no LBBB and QRS duration of 120 to 149 ms (49.6 percent).

There were no observed associations with complications.

“Although prior data regarding the effects of CRT as a function of QRS duration are largely limited to meta-analyses of clinical trials, this study provides an important perspective on the role of QRS duration in outcomes after CRT implantation in clinical practice,” the authors write.

“These findings support the use of QRS morphology and duration to help identify patients who will have the greatest benefit from CRT-D implantation.”

(JAMA. 2013;310(6):617-626; Available pre-embargo to the media at https://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, AUGUST 6, 2013

Number of Scientific Publications on Firearms Shows Modest Increase in Recent Years

“In January 1996, Congress passed an appropriations bill amendment prohibiting the U.S. Centers for Disease Control and Prevention (CDC) from using ‘funds made available for injury prevention … to advocate or promote gun control.’ This provision was triggered by evidence linking gun ownership to health harms, created uncertainty among CDC officials and researchers about what could be studied, and led to significant declines in funding,” write Joseph A. Ladapo, M.D., Ph.D., of the New York University School of Medicine, New York, and colleagues.

As reported in a Research Letter, the authors evaluated the change in the number of publications on firearms in youth compared with research on other leading causes of death before and after the Congressional action, focusing on children and adolescents because they disproportionately experience gun violence and injury. The 10 leading causes of death among children and adolescents ages 1 to 17 years were identified using CDC data on mortality between 1991 and 2010. Each cause was then matched to a Medical Subject Heading, and PubMed was searched from 1991-2010 using causes of death and child or adolescent to determine the annual number of publications.

“We only found modest increases in the number of scientific publications on firearms between 1991 and 2010, in contrast to other leading causes of death in youth. The change in number of publications on firearms was lower than anticipated compared with publications not on firearms. There was not a discrete point identified at which the pattern of publications changed. Therefore, whether the Congressional action or other events were responsible is unclear,” the authors write.

“The effect on publications after President Obama’s January 2013 memorandum directing the CDC to conduct or support research on the causes of gun violence and approaches to prevent it should be evaluated.”

(JAMA. 2013;310[5]:532-534. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Joseph A. Ladapo, M.D., Ph.D., call Lorinda Klein at 212-404-3533 or email Lorindaann.klein@nyumc.org.

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 Viewpoints Appearing in This Issue of JAMA

 Traumatic Brain Injury – An International Knowledge-Based Approach

“Traumatic brain injury [TBI] research and clinical care are decades behind other diseases, such as cancer and cardiovascular disease, and there is an important need to close existing knowledge gaps. Political will and resources are needed to create meaningful change for the global disease that is traumatic brain injury,” write Geoffrey T. Manley, M.D., Ph.D., of the University of California, San Francisco, and Andrew I. R. Maas, M.D., Ph.D., of the University of Antwerp, Belgium.

“The complexity of TBI is such that no single investigator, institution, funding organization, or private company can make progress on its own. Traumatic brain injury needs a broad-based, sustainable, multidisciplinary approach aimed at elucidating mechanisms of TBI biology, identifying risk factors, and developing treatments. First steps should include the design of longitudinal studies to follow the natural history of TBI, which should help prioritize promising avenues for research.”

(JAMA. 2013;310[5]:473-474. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Geoffrey T. Manley, M.D., Ph.D., call Juliana Bunim at 415-502-6397 or email juliana.bunim@ucsf.edu.

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 Implications of Combat Casualty Care for Mass Casualty Events

“Violence from explosives and firearms results in mass casualty events in which the injured have multiple penetrating and soft tissue injuries. Events such as those in Boston, Massachusetts; Newtown, Connecticut; and Aurora, Colorado, as well as those in other locations, such as Europe and the Middle East, demonstrate that civilian trauma may at times resemble that seen in a combat setting,” write Eric A. Elster, M.D., of the Uniformed Services University of the Health Sciences, Bethesda, Md., and colleagues. “The military has learned that implementation of evidence-based, clinical practice guidelines can reduce potentially preventable death. Certain aspects of these lessons also apply to multiple casualty scenarios in civilian settings.”

“As the United States and other nations continue to prepare for casualty scenarios from explosives or mass shooting events involving civilians, lessons from wartime trauma care and resuscitation may be helpful in planning responses. The trauma practices that have resulted from more than a decade of combat casualty care and research are transferable to the civilian world. Continuing to translate these lessons from war should provide a foundation to help reduce mortality and morbidity among civilians injured in future mass casualty events.”

(JAMA. 2013;310[5]:475-476. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Eric A. Elster, M.D., call Gwendolyn Smalls at 301-295-3981 or email gwendolyn.smalls@usuhs.edu.

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Management of Acute Stress, PTSD, and Bereavement – WHO Recommendations

“In 2010, the World Health Organization (WHO) launched the Mental Health Gap Action Program (mhGAP) Intervention Guide for nonspecialized health settings (i.e., for general health staff in first- and second-level health facilities, including primary care and district hospital settings) to address the wide treatment gap for mental disorders in low- and middle-income countries,” write Wietse A. Tol, Ph.D., of the Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues.

In this Viewpoint, the authors describe the new guidelines that expand the mhGAP Intervention Guide to include assessment and management of conditions specifically related to exposure to stress, such as acute traumatic stress, PTSD, and bereavement.

“… practitioners are offered these evidence-based guidelines to strengthen care for people exposed to extreme stress.” These new WHO guidelines are being released to coincide with publication of the JAMA Viewpoint. After the embargo time, see https://www.who.int/mental_health/resources/emergencies.

(JAMA. 2013;310[5]:477-478. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Mark van Ommeren, Ph.D., email vanommerenm@who.int.

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An Evidence-Based Response to Intimate Partner Violence – WHO Guidelines

In June 2013, the World Health Organization (WHO) published Responding to Intimate Partner Violence and Sexual Violence Against Women, providing evidence-based recommendations to guide clinicians. “This guidance is important because a clinician may be the first professional contact for persons exposed to intimate partner violence (IPV),” write Gene Feder, M.B., B.S., M.D., F.R.C.G.P., of the University of Bristol, United Kingdom, and colleagues. The guidelines are based on systematic reviews of a range of topics, including identification and approaches to providing care for women and their children after disclosure of IPV and sexual violence. In this Viewpoint, the authors summarize and discuss the IPV recommendations.

“Violence against women is a complex psychosocial and international problem. Clinicians should be part of a larger, multisystem, and coordinated solution that takes into account individual-, community-, and system-level responses, as well as a lifespan approach to violence risk assessment and prevention for those who experience IPV as well as for perpetrators. Research evidence should inform clinical actions, regardless of the disease, condition, or exposure. Although the quality of available supporting evidence is low to moderate, the new WHO guidelines provide evidence-based recommendations to assist clinicians to respond in a caring, respectful, and safe manner to women exposed to violence and may contribute to a better health care response to IPV internationally.”

(JAMA. 2013;310[5]:479-480. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Gene Feder, M.B., B.S., M.D., F.R.C.G.P., email gene.feder@bristol.ac.uk.

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

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, AUGUST 6, 2013

Media Advisory: To contact Carol S. North, M.D., M.P.E., call Russell Rian at 214-648-3404 or email russell.rian@utsouthwestern.edu.

CHICAGO – A review of articles on disaster and emergency mental health response interventions and services indicates that in postdisaster settings, a systematic framework of case identification, triage, and mental health interventions should be integrated into emergency medicine and trauma care responses, according to a study in the August 7 issue of JAMA, a theme issue on violence/human rights.

“Mental and physical consequences of major disasters have garnered increasing attention to the need for an effective community response. It is estimated that much of the U.S. population will be exposed to a … natural disaster during their lives; adding technological events such as airplane crashes and intentional human acts such as terrorism to this estimate would yield even higher numbers. Mental health effects of disaster exposures are relevant to informing care for survivors of all forms of trauma, because 9 of 10 people are likely to experience trauma in their lifetimes,” according to background information in the article. “A systematic approach to the delivery of timely and appropriate disaster mental health services may facilitate their integration into the emergency medical response.”

Carol S. North, M.D., M.P.E., of the VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, and Betty Pfefferbaum, M.D., J.D., of the University of Oklahoma Health Sciences Center, Oklahoma City, reviewed and summarized evidence to provide a practical framework for delivering mental health interventions to individuals appropriate to their needs in the wake of a disaster. A search of the peer-reviewed English-language literature on disaster mental health response yielded 222 articles that met criteria for inclusion in the review.

The authors write that “unlike physical injuries, adverse mental health outcomes of disasters may not be apparent, and therefore a systematic approach to case identification and triage to appropriate interventions is required. Symptomatic individuals in postdisaster settings may experience new-onset disaster-related psychiatric disorders, exacerbations of preexisting psychopathology and/or psychological distress. Descriptive disaster mental health studies have found that many (11 percent-38 percent) distressed individuals presenting for evaluation at shelters and family assistance centers have stress-related and adjustment disorders; bereavement, major depression, and substance use disorders were also observed, and up to 40 percent of distressed individuals had preexisting disorders.”

The researchers also found that individuals with more intense reactions to disaster stress were more likely to accept referral to mental health services than those with less intense reactions.

Standard treatments for psychiatric disorders related to trauma in general and to disasters specifically are pharmacotherapy and psychotherapy. Usual clinical practice for management of trauma-related disorders and symptoms is generally appropriate.

“Evidence-based treatments are available for patients with active psychiatric disorders, but psychosocial interventions such as psychological first aid, psychological debriefing, crisis counseling, and psychoeducation for individuals with distress have not been sufficiently evaluated to establish their benefit or harm in disaster settings,” the authors write.

“The 3 components of case identification, triage, and intervention are consistent with established approaches to emergency and medical response to mass casualty incidents and may therefore facilitate integration of mental health services into the medical disaster response.”

“Compelling issues that must be addressed in improving disaster mental health response capacities focus on matching interventions and services to specified mental health outcomes (e.g., psychiatric illness vs. disaster-related distress) for exposed and unexposed groups, encouraging the use and integration of appropriate assessment and referral, and evaluating the effectiveness of the interventions and services offered.”

(JAMA. 2013;310(5):507-518; Available pre-embargo to the media at https://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, AUGUST 6, 2013

Media Advisory: To contact Edna B. Foa, Ph.D., call Steve Graff at 215-349-5653 or email Stephen.Graff@uphs.upenn.edu. To contact editorial author Katherine Mills, Ph.D., email k.mills@unsw.edu.au.

CHICAGO – In a trial that included patients with alcohol dependence and posttraumatic stress disorder (PTSD), treatment with the drug naltrexone resulted in a decrease in the percentage of days drinking while use of the PTSD treatment, prolonged exposure therapy, was not associated with increased drinking or alcohol craving, according to a study in the August 7 issue of JAMA, a theme issue on violence/human rights.

“Alcohol dependence and PTSD are highly comorbid [co-existing], yet little is known about how best to treat this large, highly dysfunctional, and distressed population. Even though studies of treatments for alcohol dependence do not exclude patients with PTSD, symptoms of PTSD are not targeted with these treatments,” according to background information in the article. “In addition, there is a concern that prolonged exposure therapy for PTSD may exacerbate alcohol use.”

Edna B. Foa, Ph.D., of the University of Pennsylvania, Philadelphia, and colleagues compared the efficacy of naltrexone, which is an evidence-based treatment for alcohol dependence, and prolonged exposure therapy, which is an evidence-based treatment for PTSD, separately and in combination, along with supportive counseling. Prolonged exposure therapy is hypothesized to reduce drinking via amelioration (improvement) of PTSD symptoms that can lead to self-medication with alcohol. The randomized trial included 165 participants with PTSD and alcohol dependence. Participant enrollment began in February 2001 and ended in June 2009. Data collection was completed in August 2010. Participants were randomly assigned to (1) prolonged exposure therapy plus naltrexone, (2) prolonged exposure therapy plus pill placebo, (3) supportive counseling plus naltrexone, or (4) supportive counseling plus pill placebo. Prolonged exposure therapy was composed of 12 weekly 90-minute sessions followed by 6 biweekly sessions. All participants received supportive counseling. Independent evaluations occurred prior to treatment (week 0), at posttreatment (week 24), and at 6 months after treatment discontinuation (week 52).

The researchers found reductions in percentage of days drinking (PDD) in all groups during treatment. At posttreatment, patients receiving naltrexone had lower PDD (average, 5.4 percent) than patients receiving placebo (average, 13.3 percent). All groups also showed reductions in alcohol craving during treatment. “A significant main effect of naltrexone emerged at posttreatment such that the 2 naltrexone groups had less alcohol craving than the 2 placebo groups.”

All 4 groups showed reductions in PTSD symptoms during the treatment period, but the main effect of prolonged exposure therapy at posttreatment was not significant.

“Six months after the end of treatment, participants in all 4 groups had increases in percentage of days drinking. However, those in the prolonged exposure therapy plus naltrexone group had the smallest increases,” the authors write.

“Importantly, our findings indicated that prolonged exposure therapy was not associated with increased drinking or alcohol craving, a concern that has been voiced by some investigators. In fact, reduction in PTSD severity and drinking was evident for all 4 treatment groups. This finding contradicts the common view that trauma-focused therapy is contraindicated for individuals with alcohol dependence and PTSD, because it may exacerbate PTSD symptoms and thereby lead to increased alcohol use.”

“… our trial demonstrates that (l) patients with comorbid alcohol dependence and PTSD benefit from naltrexone treatment; (2) prolonged exposure therapy is not associated with exacerbation of alcohol dependence; and (3) combined treatment with naltrexone and prolonged exposure therapy may decrease the rate of relapse of alcohol dependence for up to 6 months after treatment discontinuation,” the researchers conclude.

(JAMA. 2013;310(5):488-495; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This study was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism (primary investigator: Edna B. Foa, Ph.D.).  Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, etc.

Please Note: An author podcast on this study will be available post-embargo on the JAMA website.

Editorial: Treatment of Comorbid Substance Dependence and Posttraumatic Stress Disorder

Katherine Mills, Ph.D., of the University of New South Wales, Sydney, Australia, comments on the findings of this study in an accompanying editorial.

Mills notes, “Consistent with the theory that patients with PTSD use substances to self-medicate their symptoms, patients frequently report that their PTSD symptoms are exacerbated [made worse] in the absence of substance use … As a consequence, patients in this population group have not received the care they need.”

“… the study by Foa and colleagues is a timely contribution to the literature regarding the treatment of comorbid alcohol dependence and PTSD. The study provides evidence regarding the treatment of this commonly occurring comorbidity and provides hope that the gap in treatment provision for this population may begin to narrow.”

(JAMA. 2013;310(5):482-483; Available pre-embargo to the media at https://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, AUGUST 6, 2013

Media Advisory: To contact Cynthia A. LeardMann, M.P.H., call Karl Van Orden at 619-553-9289 or email Karl.VanOrden@med.navy.mil. To contact editorial author Charles C. Engel, M.D., M.P.H., call Gwendolyn Smalls at 301-295-3981 or email gwendolyn.smalls@usuhs.edu.

CHICAGO – In an examination of risk factors associated with suicide in current and former military personnel observed 2001 and 2008, male sex and mental disorders were independently associated with suicide risk but not military-specific variables, findings that do not support an association between deployment or combat with suicide, according to a study in the August 7 issue of JAMA, a theme issue on violence/human rights.

“Despite universal access to healthcare services, mandatory suicide prevention training, and other preventive efforts, suicide has become one of the leading causes of death in the U.S. military in recent years,” according to background information in the article. “Beginning in 2005, the incidence of suicide deaths in the U.S. military began to sharply increase. Unique stressors, such as combat deployments, have been assumed to underlie the increasing incidence. Previous military suicide studies, however, have relied on case series and cross-sectional investigations and have not linked data during service with postservice periods.”

Cynthia A. LeardMann, M.P.H., of the Naval Health Research Center, San Diego, and colleagues conducted a study to identify and quantify factors associated with suicide risk in a large population of military personnel. Accrual and assessment of participants was conducted in 2001, 2004 and 2007. Questionnaire data were linked with the National Death Index and the Department of Defense Medical Mortality Registry through December 31, 2008. Participants were current and former U.S. military personnel from all service branches, including active and Reserve/National Guard, who were included in the Millennium Cohort Study (N = 151,560), a U.S. military study.

Between 2001 and 2008, there were 83 suicides among the participants in the study. In models adjusted for age and sex, factors significantly associated with increased risk of suicide included male sex, depression, manic-depressive disorder, heavy or binge drinking, and alcohol-related problems. The authors found that none of the deployment-related factors (combat experience, cumulative days deployed, or number of deployments) were associated with increased suicide risk in any of the models.

The researchers speculate that the increased rate of suicide in the military “may largely be a product of an increased prevalence of mental disorders in this population, possibly resulting from indirect cumulative occupational stresses across both deployed and home-station environments over years of war.”

“In this sample of current and former U.S. military personnel, mental health concerns but not military-specific variables were found to be independently associated with suicide risk. The findings from this study do not support an association between deployment or combat with suicide, rather they are consistent with previous research indicating that mental health problems increase suicide risk. Therefore, knowing the psychiatric history, screening for mental and substance use disorders, and early recognition of associated suicidal behaviors combined with high-quality treatment are likely to provide the best potential for mitigating suicide risk.”

(JAMA. 2013;310(5):496-506; Available pre-embargo to the media at https://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.

There will also be a digital news release available for this study, 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 6 at this link.

Editorial: Suicide, Mental Disorders, and the U.S. Military – Time to Focus on Mental Health Service Delivery

“These findings offer some potentially reassuring ways forward: the major modifiable mental health antecedents of military suicide—mood disorders and alcohol misuse—are mental disorders for which effective treatments exist,” writes Charles C. Engel, M.D., M.P.H., of the Uniformed Services University of the Health Sciences, Bethesda, Md., in an accompanying editorial.

“Furthermore, evidence-based service delivery models, particularly those involving primary care, are well known, supported by randomized trial evidence of lasting improvements in suicidal ideation among patients with depression, and designed to overcome population stigma and barriers to care.”

“However, lasting military success in the identification and treatment of the mental illness antecedents of suicide will require overcoming current overreliance on outdated combat and operational stress models of suicide prevention. Such success will also require addressing long-standing military ambivalence toward the medical model of mental illness—an ambivalence affecting service members, military clinicians, and senior leaders alike.”

(JAMA. 2013;310(5):484-485; Available pre-embargo to the media at https://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 23, 2013

Increasing Incidence of Type 1 Diabetes Among Children in Finland Appears to Have Leveled Off

“The incidence of type l diabetes (T1D), one of the most prevalent chronic diseases in children, has increased worldwide,” write Valma Harjutsalo, Ph.D., of the Diabetes Prevention Unit, Helsinki, Finland, and colleagues, who conducted a study to examine the incidence rates of T1D between 2006 and 2011 in Finnish children younger than 15 years as well as the 32-year trend (1980-2011).

As reported in a Research Letter, all children with newly diagnosed T1D were ascertained using several nationwide registers. Age-standardized and age-specific annual incidence rates for age groups 0-4, 5-9, and 10-14 years were calculated. A total of 14,069 children (7,695 boys and 6,374 girls) were diagnosed with T1D between 1980 and 2011, of whom 3,332 were new cases between 2006 and 2011. The peak incidence was observed in 2006. Analysis indicated 2 significant changes in the longer-term trend. After a modest increase until 1988, the incidence increased annually by 3.6 percent until 2005, followed by a plateau until the end of 2011.

“The encouraging observation in this study is that the incidence of T1D in Finnish children younger than 15 years has ceased to increase after a period of accelerated increase. This may be due to changes in the environment, such as vitamin D intake. The amount of vitamin D recommended for supplementation in infants had been reduced to one-tenth since the 1950s, during which time the incidence of T1D increased 5-fold. The fortification of dairy products with vitamin D after 2003 may have contributed to the leveling off of T1D incidence,” the authors write.

(JAMA. 2013;310[4]:427-428. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Valma Harjutsalo, Ph.D., email valma.harjutsalo@helsinki.fi.

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 Viewpoints Appearing in This Issue of JAMA

Note: The following two Viewpoints address this question – Should incidental findings discovered with whole-genome sequencing or testing be sought and reported to ordering clinicians and to patients (or their surrogates)?

Reporting Genomic Sequencing Results to Ordering Clinicians – Incidental, but Not Exceptional

Robert C. Green, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues write that “to date, the traditions of genetic testing and reporting have exceptionalized all genetic risk information as potentially dangerous to the well-being of patients. This tradition, in the era of genome sequencing, must be reconsidered.”

“Medical genomics has arrived, and sequencing a patient’s genome for any purpose provides an opportunity to discover unexpected but medically important information. Incidental findings in genomics should not be handled differently from other incidental findings in medicine. Rather than exceptionalize the return of incidental genomic findings, clinicians and patients should embrace them as adjuvant information of potential utility and as a welcome component of modern medical practice.”

(JAMA. 2013;310[4]:365-366. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Robert C. Green, M.D., M.P.H., call Tom Langford at 617-771-4510 or email tlangford@partners.org.

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Mandatory Extended Searches in All Genome Sequencing – ‘Incidental Findings,’ Patient Autonomy, and Shared Decision Making

Lainie Friedman Ross, M.D., Ph.D., of the University of Chicago, and colleagues write that “implementing mandatory testing for conditions beyond the scope of the original request is in conflict with key ethical principles of patient autonomy and shared decision making.”

“This is not a debate about whether truly incidental findings discovered in the course of a clinical evaluation of the genome should be discussed with patients, but whether a sample collected for the diagnostic purpose of evaluating a particular clinical question must be evaluated for a list of additional health risks even if against the wishes of the patient, the clinician, or both. Our response is a resounding no because this approach violates good clinical practice and the ethical foundations of medicine.”

(JAMA. 2013;310[4]:367-368. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Lainie Friedman Ross, M.D., Ph.D., call Michael McHugh at 773-702-3641 or email michael.mchugh@uchospitals.edu.

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Return of Secondary Genomic Findings vs. Patient Autonomy – Implications for Medical Care

In April 2013, the American College of Medical Genetics (ACMG) recommended that clinical laboratories conducting whole genome sequencing and whole exome sequencing for specific clinical indications should also analyze and report any mutations identified from a list of 57 genes considered medically actionable, regardless of whether patients wish to receive the results. “These recommendations have sparked a heated debate with profound implications for countless physicians and their patients,” write Robert Klitzman, M.D., of Columbia University, New York, and colleagues.

“Given the controversy, it is critical to consider what should be done next. Several steps appear vital. First, this debate has been occurring without sufficient data. The pathogenicity of rare variants and the prevalence and general population penetrance of true mutations in these 57 genes should be determined. Patients’ preferences for and responses to this information are currently unknown, but they are actively being sought by researchers and will probably be elucidated in the next 2 to 3 years. Input from all stakeholders should be sought, including patients, patient advocacy groups, and professional organizations such as the American Society of Clinical Oncology.”

“The ACMG policy has sparked a valuable discussion, but careful consideration and debate, continued data collection, and curation and refinement of the classification of genetic variants are all necessary to arrive at the best policy for this important medical tool. Rather than rushing to implement a policy, it seems more prudent to continue discussion, research, and analysis and ensure that all the ramifications of the policy are considered before laboratories adopt the ACMG recommendations. While proponents may argue that policy is urgently needed, such short-term benefits are outweighed by the long-range advantages of developing as optimal a policy as possible.”

(JAMA. 2013;310[4]:369-370. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Robert Klitzman, M.D., call Dacia Morris at 212-543-5421 or email Morrisd@nyspi.columbia.edu.

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 Re-envisioning Specialty Care and Payment Under Global Payment Systems

“The coming tide of payment reform as well as continued, if not escalating, cost pressures as the Affordable Care Act is implemented and an additional 30 million individuals obtain some form of health insurance present great opportunities for innovations in how health care services are organized and delivered,” write Bruce E. Landon, M.D., M.B.A., of Harvard Medical School, and David H. Roberts, M.D., of Beth Israel Deaconess Medical Center, Boston.

“For the first time in U.S. history, more patients and physicians will operate in a system in which there are defined boundaries for costs. There may be substantial shifts in how resources are spent, whether shifting from specialists to primary care physicians or from inpatient to outpatient settings. These changes will have dramatic effects on specialist practice, with implications both for how specialists practice as well as for the forms and levels of their compensation. Although changes in specialist roles and responsibilities will better align specialists with the goals of integrated care systems, with likely benefit to the health care system overall, these changes are also likely to result in substantial changes in specialist pay and number.”

(JAMA. 2013;310[4]:371-372. Available pre-embargo to the media at https://media.jamanetwork.com)

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.

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

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 23, 2013

Media Advisory: To contact Pietro Manuel Ferraro, M.D., email manuel.ferraro@channing.harvard.edu.
 

CHICAGO – An analysis of data from three studies that involved a total of more than 240,000 participants found that a self-reported history of kidney stones was associated with a statistically significant increased risk of coronary heart disease among women but no significant association was evident for men, according to a study in the July 24/31 issue of JAMA.

“Nephrolithiasis [kidney stones] is a common condition, with the prevalence varying by age and sex. A recent estimate from the National Health and Nutrition Examination Survey, a representative sample of the U.S. population, reported the prevalence of a history of kidney stones of 10.6 percent in men and 7.1 percent in women. The overall prevalence has increased from 3.8 percent (1976-1980) to 8.8 percent (2007-2010),” according to background information in the article. Kidney stone disease may be associated with an increased risk of coronary heart disease (CHD). “Previous studies of the association between kidney stones and CHD have often not controlled for important risk factors, and the results have been inconsistent.”

Pietro Manuel Ferraro, M.D., of Columbus-Gemelli Hospital, Rome, and colleagues analyzed the relation between kidney stones and risk of incident CHD for individuals with a history of kidney stones. The analysis included 45,748 men and 196,357 women in the United States without a history of CHD at baseline who were participants in the Health Professionals Follow-up Study (HPFS) (45,748 men 40-75 years of age; follow-up from 1986 to 2010), Nurses’ Health Study I (NHS I) (90,235 women 30-55 years of age; follow-up from 1992 to 2010), and Nurses’ Health Study II (NHS II) (106,122 women 25-42 years of age; follow-up from 1991 to 2009). The diagnoses of kidney stones and CHD were updated biennially during follow-up. Coronary heart disease was defined as fatal or nonfatal myocardial infarction (MI; heart attack) or coronary revascularization.

Of a total of 242,105 participants, 19,678 reported a history of kidney stones. After up to 24 years of follow-up in men and 18 years in women, 16,838 incident cases of CHD occurred. “Multivariable-adjusted analysis of individual outcomes confirmed an association in NHS I and NHS II participants between history of kidney stones and myocardial infarction and revascularization. After pooling the NHS I and NHS II cohorts, women with a history of kidney stones had an increased risk of CHD, fatal and nonfatal myocardial infarction, and revascularization,” the authors write.

After multivariable adjustment, there was no significant association between history of kidney stones and CHD in the men’s cohort.

“Our finding of no significant association between history of kidney stones and risk of CHD in men but an increased risk in women is difficult to explain, even though we could not determine whether this was due to sex or some other difference between the male and female cohorts. However, differences by sex are not infrequent in studies analyzing the association between nephrolithiasis and either CHD or risk factors for CHD,” the researchers write.

“Further research is needed to determine whether the association is sex-specific and to establish the pathophysiological basis of this association.”

(JAMA. 2013;310(4):408-415; Available pre-embargo to the media at https://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 23, 2013

Media Advisory: To contact Jon C. Tilburt, M.D., M.P.H., call Shelly Plutowski at 507-284-5005 or email newsbureau@mayo.edu. To contact editorial co-author Ezekiel J. Emanuel, M.D., Ph.D., call Katie Delach at 215-349-5964 or email Katie.Delach@uphs.upenn.edu.

CHICAGO – In a survey of about 2,500 U. S. physicians on their perceived role in addressing health care costs, they reported having some responsibility to address health care costs in their practice and expressed general agreement with quality initiatives that may also reduce cost, but expressed less enthusiasm for cost containment involving changes in payment models, according to a study in the July 24/31 issue of JAMA.

“The increasing cost of U.S. health care strains the economy. Because physicians’ decisions play a key role in overall health care spending and quality, several recent initiatives have called on physicians to reduce waste and exercise wise stewardship of resources. Given their roles, physicians’ perspectives on policies and strategies related to cost containment and their perceived responsibilities as stewards of health care resources in general are increasingly germane to recent pending and proposed policy reforms,” according to background information in the article.

Jon C. Tilburt, M.D., M.P.H., of the Mayo Clinic, Rochester, Minn., and colleagues conducted a survey of physicians about their views on several potential proposed policies and strategies to contain health care spending, assessed physicians’ perceived roles and responsibilities in addressing health care costs, and ascertained physician characteristics associated with those views. The survey was mailed in 2012 to 3,897 U.S. physicians randomly selected from the American Medical Association Masterfile. A total of 2,556 physicians responded (response rate = 65 percent). The survey included respondents rating their level of enthusiasm (not, somewhat, or very enthusiastic) toward 17 specific means of reducing health care costs, including but not limited to strategies proposed in the Patient Protection and Affordable Care Act; and agreement with an 11-measure cost-consciousness scale.

The researchers found that most respondents believed that trial lawyers (60 percent), health insurance companies (59 percent), hospitals and health systems (56 percent), pharmaceutical and device manufacturers (56 percent), and patients (52 percent) have a “major responsibility” for reducing health care costs, whereas only 36 percent reported that practicing physicians have “major responsibility.” Most physicians were “very enthusiastic” for “promoting continuity of care” (75 percent), “expanding access to quality and safety data” (51 percent), and “limiting access to expensive treatments with little net benefit” (51 percent) as a means of reducing health care costs.

Few respondents expressed enthusiasm for “eliminating fee-for-service payment models” (7 percent). “Most physicians reported being ‘aware of the costs of the tests/treatments [they] recommend’ (76 percent), agreed they should adhere to clinical guidelines that discourage the use of marginally beneficial care (79 percent), and agreed that they ‘should be solely devoted to individual patients’ best interests, even if that is expensive’ (78 percent) and that ‘doctors need to take a more prominent role in limiting use of unnecessary tests’ (89 percent),” the authors write.

Most physicians (85 percent) disagreed that they “should sometimes deny beneficial but costly services to certain patients because resources should go to other patients that need them more.” In models testing associations with enthusiasm for key cost-containment strategies, having a salary plus bonus or salary-only compensation type was independently associated with enthusiasm for “eliminating fee for service.” Also, group or government practice setting and having a salary plus bonus compensation type were positively associated with cost-consciousness.

“U.S. physicians’ opinions about their role in containing health care costs are complex. In this survey, we found that they express considerable enthusiasm for several proposed cost-containment strategies that aim to enhance or promote high-quality care such as improved continuity of care. However, there is considerably less enthusiasm for more substantial financing reforms, including bundled payments, penalties for readmissions, and eliminating fee-for-service reimbursement; Medicare pay cuts are unpopular across the board. They were also more likely to identify other groups, rather than physicians, such as insurers, lawyers, hospitals, and health systems, as having a major responsibility to reduce cost. These data document professional sentiments about addressing health care costs and speak directly to the acceptability of several key policy strategies for curbing those costs,” the authors write.

“Moving toward cost-conscious care in the current environment in which physicians practice starts with strategies for which there is widespread physician support might create momentum for such efforts, including improving quality and efficiency of care and bringing transparent cost information and evidence from comparative effectiveness research into electronic health records with decision support technology. More aggressive (and potentially necessary) financing changes may need to be phased in, with careful monitoring to ensure that they do not infringe on the integrity of individual clinical relationships.”

(JAMA. 2013;310(4):380-388; Available pre-embargo to the media at https://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.

There will also be a digital news release available for this study, 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 23 at this link.

Editorial: Will Physicians Lead on Controlling Health Care Costs?

Ezekiel J. Emanuel, M.D., Ph.D., and Andrew Steinmetz, B.A., of the University of Pennsylvania, Philadelphia, write in an accompanying editorial that the findings of this survey “are somewhat discouraging.”

“The findings suggest that physicians do not yet have that ‘all-hands-on-deck’ mentality this historical moment demands. Indeed, the survey of 2,556 physicians suggests that in the face of this new and uncertain moment in the reform of the health care system, physicians are lapsing into the well-known, cautious instinctual approaches humans adopt whenever confronted by uncertainty: blame others and persevere with ‘business as usual.’”

“The next decade requires ‘all hands on deck’ to create meaningful, lasting change in health care. The study by Tilburt et al indicates that the medical profession is not there yet — that many physicians would prefer to sit on the sidelines while other actors in the health care system do the real work of reform. This could marginalize and demote physicians. Physicians must commit themselves to act like the captain of the health care ship and take responsibility for leading the United States to a better health care system that provides higher-quality care at lower costs.”

(JAMA. 2013;310(4):374-375; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr. Emanuel reported receiving payment for speaking engagements unrelated to this work.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 23, 2013

Media Advisory: To contact corresponding author Matthew J. Kuehnert, M.D., call Melissa Dankel at 404-639-4718 or email mdankel@cdc.gov. To contact editorial author Daniel R. Kaul, M.D., call Shantell Kirkendoll at 734-764-2220 or email smkirk@umich.edu.

CHICAGO – An investigation into the source of a fatal case of raccoon rabies virus exposure indicates the individual received the virus via a kidney transplant 18 months earlier, findings suggesting that rabies transmitted by this route may have a long incubation period, and that although solid organ transplant transmission of infectious encephalitis is rare, further education to increase awareness is needed, according to a study in the July 24/31 issue of JAMA.

The rabies virus causes a fatal encephalitis (inflammation of the brain) and can be transmitted through tissue or organ transplantation. “Unique rabies virus variants, distinguishable by molecular typing methods, are associated with specific animal reservoirs. Globally, an estimated 55,000 persons die of rabies every year, with most transmission attributable to dog bites. Approximately 2 human rabies deaths are reported in the United States every year and during 2000 through 2010, all but 2 domestically acquired cases were associated with bats. Despite raccoons being the most frequently reported rabid animal in the United States, only l human rabies case associated with the raccoon rabies virus variant has been reported,” according to background information in the article. In February 2013, a kidney recipient with no reported exposures to potentially rabid animals died from rabies 18 months after transplantation.

Neil M. Vora, M.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues conducted a study to determine whether organ transplantation was the source of rabies virus exposure in the kidney recipient, and to evaluate for and prevent rabies in other transplant recipients (n = 3; right kidney, heart, and liver) from the same donor. Organ donor and all transplant recipient medical records were reviewed. Laboratory tests to detect rabies virus-specific binding antibodies, rabies virus neutralizing antibodies, and rabies virus antigens were conducted on available specimens, including serum, cerebrospinal fluid, and tissues from the donor and the recipients.

The researchers found that in retrospect, the kidney donor’s symptoms prior to death were consistent with rabies (the presumed diagnosis at the time of death was ciguatera poisoning [a foodborne illness]). Subsequent interviews with family members revealed that the donor had significant wildlife exposure, and had sustained at least 2 raccoon bites, for which he did not seek medical care. Rabies virus antigen was detected in archived autopsy brain tissue collected from the donor. The rabies viruses infecting the donor and the deceased kidney recipient were consistent with the raccoon rabies virus variant and were more than 99.9 percent identical across the entire N gene, thus confirming organ transplantation as the route of transmission.

The 3 other organ recipients did not have signs or symptoms consistent with rabies or encephalitis. They have remained asymptomatic, with rabies virus neutralizing antibodies detected in their serum after completion of postexposure prophylaxis.

“This transmission event provides an opportunity for enhancing rabies awareness and recognition and highlights the need for a modified approach to organ donor screening and recipient monitoring for infectious encephalitis. This investigation also underscores the importance of collaboration between clinicians, epidemiologists, and laboratory scientists,” the authors write.

(JAMA. 2013;310(4):398-407; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This investigation was supported by the Centers for Disease Control and Prevention, Maryland Department of Health and Mental Hygiene, North Carolina Division of Public Health, and Florida Department of Health and funded as part of routine infectious disease outbreak investigation activities. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of interest and none were reported.

Editorial: Donor-Derived Infections With Central Nervous System Pathogens After Solid Organ Transplantation

In an accompanying editorial, Daniel R. Kaul, M.D., of the University of Michigan Medical School, Ann Arbor, writes that during the past decade, numerous instances have been reported of donor-derived infection among recipients of solid organ transplants with pathogens associated with central nervous system (CNS) infections, including the West Nile virus and rabies virus.

“Educational efforts to improve recognition of donors with CNS infection and the risks associated with using these donors should be directed not just at the transplant community but at the larger community of physicians involved in the care of potential donors—particularly critical care specialists, neurologists, and infectious disease physicians. These clinicians may not be aware of the potential for donor-derived infection, but accepting transplant centers must rely on the clinical impression of those caring for the potential donor. Although the risk of donor-derived disease is inherent in the process of organ transplantation and cannot be eliminated, raising awareness of the risk of using donors with undiagnosed CNS infection is the best way to reduce the occurrence of these transmissions.”

(JAMA. 2013;310(4):378-379; Available pre-embargo to the media at https://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 23, 2013

Media Advisory: To contact Jeffrey H. Silber, M.D., Ph.D., call Dana Mortensen at 267-426-6092 or email mortensen@email.chop.edu. To contact editorial co-author Jeanne S. Mandelblatt, M.D., M.P.H., call Karen Mallet at 215-514-9751 or email km463@georgetown.edu.

CHICAGO – In an analysis of 5-year survival rates among black and white women diagnosed with breast cancer between 1991 and 2005, black women continued to have a lower rate of survival, with most of the difference related to factors including poorer health of black patients at diagnosis and more advanced disease, rather than treatment differences, according to a study in the July 24/31 issue of JAMA.

“For 20 years health care investigators in the United States have been keenly aware of racial disparities in survival among women with breast cancer. Numerous reports have not only identified and documented worse outcomes in black patients with breast cancer but have suggested potential reasons for the disparities based on differences in screening, presentation, comorbid conditions on presentation, tumor biology, stage, treatment, and socioeconomic status,” according to background information in the article.

Jeffrey H. Silber, M.D., Ph.D., of the Children’s Hospital of Philadelphia, and colleagues examined the extent of the racial differences in breast cancer survival in the Medicare population and the reasons the disparity exists. The study compared 7,375 black women 65 years and older diagnosed between 1991 to 2005 and 3 sets of 7,375 matched white control patients selected from 99,898 white potential control patients, using data from 16 U.S. Surveillance, Epidemiology and End Results (SEER) sites in the SEER-Medicare database. All patients received follow-up through December 2009 and the black case patients were matched to 3 white control populations on demographics (age, year of diagnosis, and SEER site), presentation (demographics variables plus patient comorbid conditions and tumor characteristics such as stage, size, grade, and estrogen receptor status), and treatment (presentation variables plus details of surgery, radiation therapy, and chemotherapy).

The researchers found that the absolute difference in 5-year survival (blacks, 55.9 percent; whites, 68.8 percent) was 12.9 percent in the demographics match. This difference remained unchanged between 1991 and 2005. After matching on presentation characteristics, the absolute difference in 5-year survival was 4.4 percent and was 3.6 percent lower for blacks than for whites matched also on treatment.

Regarding differences in treatment by race, overall, 12.6 percent of black patients did not have evidence of receiving any treatment for their breast cancer, compared with 5.9 percent of whites. Average time from diagnosis to treatment was longer among blacks than among demographics-matched whites, 29.2 days vs 22.5 days. Blacks were also more likely to have long delays in treatment: 5.8 percent of blacks did not initiate treatment within the first 3 months from diagnosis, compared to 2.5 percent of white patients. Blacks also received breast-conserving surgery without any other treatment more often than presentation-matched whites (8.2 percent vs 7.3 percent). “Nevertheless, differences in survival associated with treatment differences accounted for only 0.81 percent of the 12.9 percent survival difference,” the authors write.

There were large differences in the way black and white patients presented. “For the demographics match, blacks had significantly less evidence of at least l primary care visit than matched whites (80.5 percent vs 88.5 percent, respectively); significantly lower rates of breast cancer screening (23.5 percent vs 35.7 percent); and significantly lower rates of colon cancer and cholesterol screening,” the authors write.

“Our results suggest that it may be difficult to eliminate the racial disparity in survival from diagnosis unless differences in presentation can be reduced. There is also a disparity in treatment, with blacks receiving treatment inferior to that received by whites with similar presentation, but this explains only a small part of the observed difference in survival. The disparity in treatment might matter more if the disparity in presentation were reduced, because blacks would then be diagnosed with less advanced disease, for which treatment is more effective.”

The researchers add that black patients are diagnosed not only with more advanced breast cancers but also with more unrelated comorbid conditions. “Some of the effectiveness of cancer treatment for blacks may be blunted by other health problems. If the differences in comorbid conditions at diagnosis were reduced, it is possible that the differences in cancer treatment would matter more for the differences in survival.”
(JAMA. 2013;310(4):389-397; Available pre-embargo to the media at https://media.jamanetwork.com)

Editor’s Note: This research was funded through a grant from the Agency for Healthcare Research and Quality, Department of Health and Human Services, and by the U.S. National Science Foundation. This study used the linked SEER-Medicare database. All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Editorial: Black-White Differences in Breast Cancer Outcomes Among Older Medicare Beneficiaries – Does Systemic Treatment Matter?

Jeanne S. Mandelblatt, M.D., M.P.H., of the Georgetown Lombardi Comprehensive Cancer Center, Washington, D.C., and colleagues comment on the findings of this study in an accompanying editorial.

“The rigorous study by Silber et al provides additional clues to the black-white differences in breast cancer outcomes. Ultimately, for any cancer control strategy to succeed, improved care quality appears to be a necessary, but not sufficient, condition to eliminate race-based mortality differences in the United States.”

(JAMA. 2013;310(4):376-377; Available pre-embargo to the media at https://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 16, 2013

Survival Poor For Nursing Home Residents With Advanced Cognitive Impairment Who Undergo Multiple Hospitalizations For Infections or Dehydration

“Multiple hospitalizations for complications from a terminal illness may be burdensome for elderly patients and reflect poor quality care,” write Joan M. Teno, M.D., M.S., of the Warren Alpert School of Medicine of Brown University, Providence, R.I., and colleagues, who conducted a study to examine whether the occurrence of multiple hospitalizations for the complications of infections or dehydration was associated with survival.

As reported in a Research Letter, the study population was identified using data from the national Minimum Data Set repository, which includes standardized assessments regularly completed by staff on all nursing home (NH) residents in the United States between January 2000 and December 2008. The researchers identified the first baseline assessment in which a resident had a Cognitive Performance Score of 4, 5, or 6 indicating moderate to very severe cognitive impairment. Residents were followed up for l year from the baseline assessment date (through 2009), and residents were identified who had 2 or more hospitalizations for the same type of the following diagnoses: pneumonia, urinary tract infection (UTI), septicemia, or dehydration or malnutrition.

Between 2000 and 2008, 1.3 million NH residents attained a Cognitive Performance Score of 4, 5, or 6 and survived at least 30 days after that assessment. Compared with overall survival (476 days), the adjusted survival was significantly lower for all of the burdensome transitions: pneumonia, 95 days; UTI, 146 days; dehydration or malnutrition, 111 days; and septicemia, 89 days.

“Future research is needed to understand whether these transitions are based on financial incentives, poor communication, or a lack of resources needed to diagnose and treat a NH resident,” the authors write. “… the observed survival suggests that the first hospitalization with these diagnoses for NH residents with advanced cognitive impairment should result in reconsideration of the goals of care and the appropriateness of continued hospitalizations.”

(JAMA. 2013;310[3]:319-320. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact Joan M. Teno, M.D., M.S., call David Orenstein at 401-863-1862 or email david_orenstein@brown.edu.

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 Viewpoints Appearing in This Issue of JAMA

 The International Registry Infrastructure for Cardiovascular Device Evaluation and Surveillance

Art Sedrakyan, M.D., Ph.D., of Weill Cornell Medical College, Cornell University, New York, and colleagues summarize “the potential for development of an International Consortium of Cardiovascular Registries, modeled on a consortium established for orthopedic devices, as an initial project in the realm of cardiovascular devices with the focus on transcatheter aortic valve replacement (TAVR).”

“… a global consortium of cardiovascular device registries has great potential to improve the public health, facilitate and strengthen regulatory processes, and advance clinical practice using innovative approaches. The exploration of the new International Consortium of Cardiovascular Registries focused on the novel technology of TAVR has multiple potential scalable positive outcomes for a larger cardiovascular initiative. The initiative may improve collaboration of the different stakeholders and enhance efficiency of registries and could facilitate the evaluation of the safety and efficacy of new devices and approaches, thereby reaching the goal of harnessing the global knowledge.”

(JAMA. 2013;310[3]:257-258. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact corresponding author Danica Marinac-Dabic, M.D., Ph.D., call Synim Rivers at 301-796-8729 or email Synim.Rivers@fda.hhs.gov.

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New Incentive-Based Programs – Maryland’s Health Disparities Initiatives

In this Viewpoint, E. Albert Reece, M.D., Ph.D., M.B.A., of the University of Maryland School of Medicine, Baltimore, and colleagues discuss the Maryland Health Improvement and Disparities Reduction Act of 2012, which includes incentive-based strategies to address health and health care disparities.

“The use of incentives to address disparities links progress to the change underway in the health care system. During this transition, tracking and monitoring health inequity, although essential, is insufficient. Efforts to move health care forward must not leave behind communities with longstanding disadvantages in health. Incentives can create the environment in which innovation and creativity forge new paths to progress.”

(JAMA. 2013;310[3]:259-260. Available pre-embargo to the media at https://media.jamanetwork.com)

Media Advisory: To contact E. Albert Reece, M.D., Ph.D., M.B.A., call Karen Robinson at 410-706-7590 or email KRobinson@som.umaryland.edu.

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

For More Information: contact The JAMA Network^® Media Relations Department at 312-464-JAMA (5262) or email mediarelations@jamanetwork.org.

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EMBARGOED FOR RELEASE: 3 P.M. (CT) TUESDAY, JULY 16, 2013

Media Advisory: To contact Spyros D. Mentzelopoulos, M.D., email sdmentzelopoulos@yahoo.com.

CHICAGO – Among patients who experienced in-hospital cardiac arrest requiring vasopressors (drugs that increase blood pressure), use of a combination therapy during cardiopulmonary resuscitation resulted in improved survival to hospital discharge with favorable neurological status, according to a study in the July 17 issue of JAMA.

“Neurological outcome after cardiac arrest has been the main end point of several randomized clinical trials (RCTs).  Neurologically favorable survival differs from overall survival. Among cardiac arrest survivors, the prevalence of severe cerebral disability or vegetative state ranges from 25 percent to 50 percent. In a previous single-center RCT, combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR vs. epinephrine [adrenaline] alone during CPR and no steroids resulted in improved overall survival to hospital discharge,” according to background information in the article. “However, this preliminary study could not reliably assess vasopressin-steroids-epinephrine (VSE) efficacy with respect to neurologically favorable survival to hospital discharge.”

Spyros D. Mentzelopoulos, M.D., Ph.D., of the University of Athens Medical School, Athens, Greece, and colleagues conducted a study to determine whether combined vasopressin-epinephrine during CPR and corticosteroid supplementation during and after CPR improved survival to hospital discharge with a favorable neurological score on the Cerebral Performance Category (CPC). The randomized, placebo-controlled trial was performed from September 2008 to October 2010 in 3 tertiary care centers in Greece and included 268 patients with cardiac arrest requiring epinephrine according to resuscitation guidelines.

Patients received either vasopressin plus epinephrine (VSE group, n = 130) or saline placebo plus epinephrine (control group, n = 138) for the first 5 CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the VSE group received methyl prednisolone and patients in the control group received saline placebo. Shock after resuscitation was treated with stress-dose hydrocortisone (VSE group, n = 76) or saline placebo (control group, n = 73). The primary outcomes for the study were return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2.

Patients in the VSE group had a higher probability for ROSC for 20 minutes or longer compared with patients in the control group (109/130 [83.9 percent] vs. 91/138 [65.9 percent]). Compared with patients in the control group, patients in the VSE group had a lower risk of poor outcome during follow-up and were more likely to be alive at hospital discharge with favorable neurological recovery (18/130 [13.9 percent] vs. 7/138 [5.1 percent]).

Among survivors for 4 hours or longer, VSE patients with postresuscitation shock (n = 76) vs. corresponding controls (n = 73) had a lower risk of poor outcome during follow-up and were more likely to be alive at hospital discharge with favorable neurological recovery (16/76 [21.1 percent] vs. 6/73 [8.2 percent]).

Post-arrest illness and complications throughout hospital stay and death causes were similar among survivors for 4 hours or longer.

“In this study of patients with cardiac arrest requiring vasopressors, the combination of vasopressin and epinephrine, along with methylprednisolone during CPR and hydrocortisone in postresuscitation shock, resulted in improved survival to hospital discharge with favorable neurological status, compared with epinephrine and saline placebo. These results are consistent with increased efficacy of the VSE combination vs. epinephrine alone during CPR for in-hospital, vasopressor-requiring cardiac arrest,” the authors write.

(JAMA. 2013;310(3):270-279; Available pre-embargo to the media at https://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 16, 2013

Media Advisory: To contact corresponding author Samy Suissa, Ph.D., call Tod Hoffman at 514-340-8222, ext. 8661 or email thoffman@jgh.mcgill.ca.

CHICAGO – In a study that included more than 10,000 men with nonmetastatic prostate cancer, use of androgen deprivation therapy (ADT) was associated with a significantly increased risk of acute kidney injury, with variations observed with certain types of ADTs, according to a study in the July 17 issue of JAMA.

“Androgen deprivation therapy is the mainstay treatment for patients with advanced prostate cancer. While this therapy has been traditionally reserved for patients with advanced disease, ADT is increasingly being used in patients with less severe forms of the cancer, such as in patients with biochemical relapse who have no evidence of metastatic disease. Although ADT has been shown to have beneficial effects on prostate cancer progression, serious adverse events can occur during treatment,” according to background information in the article. “… the testosterone suppression associated with this therapy may lead to a hypogonadal condition that can have detrimental effects on renal function, thus raising the hypothesis that ADT-induced hypogonadism could potentially lead to acute kidney injury (AKI).” The mortality rate is high for patients with AKI (around 50 percent).

Francesco Lapi, Pharm.D., Ph.D., of Jewish General Hospital, Montreal, Canada, and colleagues conducted a study to determine whether the use of ADT was associated with an increased risk of AKI in patients newly diagnosed with prostate cancer. The researchers used medical information extracted from the UK Clinical Practice Research Datalink linked to the Hospital Episodes Statistics database. The study included men newly diagnosed with nonmetastatic prostate cancer between January 1997 and December 2008 who were followed up until December 2009. Cases were patients with incident AKI during follow-up who were randomly matched with up to 20 controls on age, calendar year of prostate cancer diagnosis, and duration of follow-up. Analysis was conducted to estimate the odds ratios of AKI associated with the use of ADT. ADT was categorized into 1 of 6 mutually exclusive groups: gonadotropin-releasing hormone agonists, oral antiandrogens, combined androgen blockade, bilateral orchiectomy, estrogens, and combination of the above.

A total of 10,250 patients met the study inclusion criteria. During follow-up, 232 cases with a first-ever AKI admission were identified. All cases were matched with at least l control. The researchers found that compared with never use, current use of ADT was significantly associated with a 2.5 times increased odds of AKI. “This association was mainly driven by a combined androgen blockade consisting of gonadotropin-releasing hormone agonists with oral antiandrogens, estrogens, other combination therapies, and gonadotropin-releasing hormone agonists.”

“To our knowledge, this is the first population-based study to investigate the association between the use of ADT and the risk of AKI in men with prostate cancer. In this study, the use of ADT was associated with an increased risk of AKI, with variations observed with certain types of ADTs. This association remained continuously elevated, with the highest odds ratio observed in the first year of treatment. Overall, these results remained consistent after conducting several sensitivity analyses,” the authors write.

“These findings require replication in other carefully designed studies as well as further investigation of their clinical importance.”

(JAMA. 2013;310(3):289-296; Available pre-embargo to the media at https://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 16, 2013

Media Advisory: To contact corresponding author Robert W. Haley, M.D., call Russell Rian at 214-648-3404 or email russell.rian@utsouthwestern.edu. To contact Lyle R. Petersen, M.D., M.P.H., call Candice Hoffmann at 404-639-7689 or email hqx5@cdc.gov. To contact editorial author Stephen M. Ostroff, M.D., email sostroff@verizon.net.

CHICAGO – An analysis of West Nile virus epidemics in Dallas County in 2012 and previous years finds that the epidemics begin early, after unusually warm winters; are often in similar geographical locations; and are predicted by the mosquito vector index (an estimate of the average number of West Nile virus-infected mosquitoes collected per trap-night), information that may help prevent future outbreaks of West Nile virus-associated illness, according to a study in the July 17 issue of JAMA.

“After declining over the prior 5 years, mosquito-borne West Nile virus infection resurged in 2012 throughout the United States, most substantially in Dallas County, Texas. Dallas has been a known focus of mosquito-borne encephalitis since 1966, when a large epidemic of St. Louis encephalitis (SLE) occurred there, necessitating aerial spraying of insecticide for control,” according to background information in the article. “With the introduction of West Nile virus into New York City in 1999 and its subsequent spread across the country, West Nile virus appears to have displaced SLE virus. Dallas recognized its initial cases of West Nile virus encephalitis in 2002 and its first sizeable outbreak in 2006, followed by 5 years of low West Nile virus activity. In the 2012 nationwide West Nile virus resurgence, Dallas County experienced the most West Nile virus infections of any U.S. urban area, requiring intensified ground and aerial spraying of insecticides.”

Wendy M. Chung, M.D., S.M., of Dallas County Health and Human Services, Dallas, and colleagues conducted a study to examine the features associated with the West Nile virus epidemics and to identify surveillance and control measures for minimizing future outbreaks. The researchers analyzed surveillance data from Dallas County (population, 2.4 million), which included the numbers of residents diagnosed with West Nile virus infection between May 30, 2012 and December 3, 2012; mosquito trap results; weather data; and syndromic (pertaining to symptoms and syndromes) surveillance from area emergency departments.

From May 30 through December 3, 2012, patients (n = 1,162) with any West Nile virus-positive test result were reported to the health department; 615 met laboratory case criteria, and 398 cases of West Nile virus illness with 19 deaths were confirmed by clinical review in residents of Dallas County. The outbreak included 173 patients with West Nile neuroinvasive disease (WNND) and 225 with West Nile fever, and 17 West Nile virus-positive blood donors. Regarding patients with WNND, 96 percent were hospitalized; 35 percent required intensive care; 18 percent required assisted ventilation; and the case-fatality rate was 10 percent. The overall WNND incidence rate in Dallas County was 7.30 per 100,000 residents in 20l2, compared with 2.91 in 2006.

The first West Nile virus-positive mosquito pool of 2012 was detected in late May, earlier than in typical seasons. Symptoms of the first 19 cases of WNND in 2012 began in June, a month earlier than in most prior seasons; thereafter, the number of new cases escalated rapidly. Sequential increases in the weekly vector index early in the 2012 season significantly predicted the number of patients with onset of symptoms of WNND in the subsequent l to 2 weeks.

The 2012 epidemic year was distinguished from the preceding 10 years by the mildest winter, as indicated by absence of hard winter freezes, the most degree-days above daily normal temperature during the winter and spring and other features. During the 11 years since West Nile virus was first identified in Dallas, the researchers found that the annual prevalence of WNND was inversely associated with the number of days with low temperatures below 28°F in December through February.

“Although initially widely distributed, WNND cases soon clustered in neighborhoods with high housing density in the north central area of the county, reflecting higher vector indices and following geospatial patterns of West Nile virus in prior years,” the authors write.

Aerial insecticide spraying was not associated with increases in emergency department visits for respiratory symptoms or skin rash.

“This report identifies several distinguishing features of a large urban West Nile virus outbreak that may assist future prevention and control efforts for vector-borne infections,” the authors write. “Consideration of weather patterns and historical geographical hot spots and acting on the vector index may help prevent West Nile virus-associated illness.”

(JAMA. 2013;310(3):297-307; Available pre-embargo to the media at https://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.

There will also be a digital news release available for this study, 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 16 at this link.

Review Article Describes Epidemiology, Characteristics and Prevention of West Nile Virus

Lyle R. Petersen, M.D., M.P.H., of the Centers for Disease Control and Prevention, U.S. Public Health Service, Department of Health and Human Services, Fort Collins, Colo., and colleagues conducted a review of the medical literature and national surveillance data to examine the ecology, virology, epidemiology, clinical characteristics, diagnosis, prevention, and control of West Nile virus.

“West Nile virus has become endemic in all 48 contiguous United States as well as all Canadian provinces since its discovery in North America in New York City in 1999. It has produced the 3 largest arbovirai neuroinvasive disease (encephalitis, meningitis, or acute flaccid paralysis) outbreaks ever recorded in the United States, with nearly 3,000 cases of neuroinvasive disease recorded each year in 2002, 2003, and 2012,”according to background information in the article.

The authors found that since 1999, there have been 16,196 human neuroinvasive disease cases and 1,549 deaths reported; more than 780,000 illnesses have likely occurred. Incidence is highest in the Midwest from mid-July to early September. “West Nile fever develops in approximately 25 percent of those infected, varies greatly in clinical severity, and symptoms may be prolonged. Neuroinvasive disease (meningitis, encephalitis, acute flaccid paralysis) develops in less than 1 percent but carries a fatality rate of approximately 10 percent. Encephalitis has a highly variable clinical course but often is associated with considerable long-term morbidity. Approximately two-thirds of those with paralysis remain with significant weakness in affected limbs.”

The authors add that diagnosis usually rests on detection of IgM antibody in serum or cerebrospinal fluid. No licensed human vaccine exists. “Prevention uses an integrated pest management approach, which focuses on surveillance, elimination of mosquito breeding sites, and larval and adult mosquito management using pesticides to keep mosquito populations low. During outbreaks or impending outbreaks, emphasis shifts to aggressive adult mosquito control to reduce the abundance of infected, biting mosquitoes. Pesticide exposure and adverse human health events following adult mosquito control operations for West Nile virus appear negligible.”

“The resurgence of West Nile virus in 2012 after several years of decreasing incidence in the United States suggests that West Nile virus will continue to produce unpredictable local and regional outbreaks,” the researchers write. “… sustainable community-based surveillance and vector management programs are critical, particularly in metropolitan areas with a history of West Nile virus and large human populations at risk.”

(JAMA. 2013;310[3]:308-315. Available pre-embargo to the media at https://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: West Nile Virus – Too Important to Forget

“Periodic flares of West Nile virus, as occurred in 2012, certainly will recur,” writes Stephen M. Ostroff, M.D., formerly of the Centers for Disease Control and Prevention, Atlanta, and the Pennsylvania Department of Health, Harrisburg, in an accompanying editorial.

“Where future outbreaks of the virus will occur and how intense they will be is difficult to predict, especially in light of declining surveillance efforts and vector monitoring programs. Unusually warm winters, as occurred in Dallas during 2011-2012, are becoming more common and will favor additional West Nile virus events like the one described by Chung et al. Changing weather patterns raise the possibility of expanded zones of risk and longer transmission seasons. The tragic consequences of the Dallas West Nile virus epidemic must not be forgotten, for they serve as a cogent reminder of the need to sustain vector monitoring and prevention programs in all communities.”

(JAMA. 2013;310(3):267-268; Available pre-embargo to the media at https://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 16, 2013

Media Advisory: To contact Jared P. Reis, Ph.D., call the NHLBI Communications Office at 301-496-4236 or email nhlbi_news@nhlbi.nih.gov.

CHICAGO – In a study of adults recruited and followed up over the past 3 decades in the United States, longer duration of overall and abdominal obesity beginning in young adulthood was associated with higher rates of coronary artery calcification, a subclinical predictor of coronary heart disease, according to a study in the July 17 issue of JAMA.

“Subclinical atherosclerosis, identified by the presence of coronary artery calcification (CAC), progresses over time, and predicts the development of coronary heart disease events,” according to background information in the article. The degree of overall and abdominal obesity, as reflected by an increased body mass index (BMI) and waist circumference, respectively, are important risk factors for the presence and progression of CAC. “Understanding the influence of the duration of obesity or the presence or progression of atherosclerosis is critical, given the obesity epidemic. With a doubling of obesity rates for adults and a tripling of rates for adolescents during the last 3 decades, younger individuals are experiencing a greater cumulative exposure to excess adiposity during their lifetime. However, few studies have determined the consequences of long-term obesity,” the authors write.

Jared P. Reis, Ph.D., of the National Heart, Lung, and Blood Institute, Bethesda, Md., and colleagues conducted a study to investigate whether the duration of overall and abdominal obesity was associated with the presence and 10-year progression of CAC. The study included 3,275 white and black adults 18 to 30 years of age at the beginning of the study period in 1985-1986 who did not initially have overall obesity (BMI ≥30) or abdominal obesity (men; waist circumference [WC] >40.2 inches; women: >34.6 inches) in the multicenter, community-based Coronary Artery Risk Development in Young Adults (CARDIA) study. Participants completed computed tomography scanning for the presence of CAC during the 15-, 20-, or 25-year follow-up examinations. Duration of overall and abdominal obesity was calculated using repeat measurements of BMI and WC, respectively, performed 2, 5, 7, 10, 15, 20, and 25 years after the beginning of the study.

Of the 3,275 eligible participants, 45.7 percent were black and 50.6 percent were women. During followup, 40.4 percent and 41.0 percent developed overall and abdominal obesity, respectively; the average duration of obesity was 13.3 years and 12.2 years for those who developed overall and abdominal obesity, respectively.

Overall, CAC was present in 27.5 percent (n = 902) of participants. The researchers found that the presence and extent of CAC were associated with duration of overall and abdominal obesity. “Approximately 38.2 percent and 39.3 percent of participants with more than 20 years of overall and abdominal obesity, respectively, had CAC compared with 24.9 percent and 24.7 percent of those who never developed overall or abdominal obesity,” the researchers write. “Extensive CAC was present in 6.5 percent and 9.0 percent of those with more than 20 years of overall and abdominal obesity, respectively, compared with 5.7 percent and 5.3 percent of those who never developed overall or abdominal obesity, respectively.”

The rates of CAC were higher with a longer duration of overall obesity and abdominal obesity. Approximately 25.2 percent and 27.7 percent of those with more than 20 years of overall and abdominal obesity, respectively, experienced progression of CAC compared with 20.2 percent and 19.5 percent of those with 0 years.

“In conclusion, in this study a longer duration of overall and abdominal obesity beginning in young adulthood was associated with CAC and its 10-year progression through middle age independent of the degree of adiposity,” the authors write. “These findings suggest that the longer duration of exposure to excess adiposity as a result of the obesity epidemic and an earlier age at onset will have important implications on the future burden of coronary atherosclerosis and potentially on the rates of clinical cardiovascular disease in the United States.”

(JAMA. 2013;310(3):280-288; Available pre-embargo to the media at https://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: An author podcast on this study will be available post-embargo on the JAMA website.

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