Idaho Medical News

In a one-day snapshot of intensive care units around the world, more than half of the patients had acquired an infection during their stay, a major study revealed.
And the mortality rate among infected patients was more than double that of patients without an infection, according to Jean-Louis Vincent, MD, PhD, of Erasme University Hospital in Brussels, and colleagues.
The findings come from the Extended Prevalence of Infection in Intensive Care (EPIC II) study, which collected data over a 24-hour period from 1,265 intensive care units in 75 countries on May 8, 2007, the researchers reported in the Dec. 2 issue of the Journal of the American Medical Association.
The study is a follow-up to an earlier one-day snapshot of ICU infections in Western Europe, the European Prevalence of Infection in Intensive Care study, conducted on April 29, 1992.
The prevalence of infection is important because of the increased risk of death, according to co-author John Marshall, MD, of St. Michael’s Hospital in Toronto.

“There is an additional perhaps 10% to 15% mortality risk associated with acquiring an infection in the ICU,” Marshall said. For that reason, he said, prevention strategies “assume a substantial degree of importance when you look at this as a global health problem.”

The study also offers “several noteworthy insights into the current practice patterns of antibiotic use and infection risks in ICU patients,” according to Steven Opal, MD, of Warren Alpert Medical School of Brown University in Providence, R.I., and Thierry Calandra, MD, PhD, of Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland.

In an accompanying editorial, they said the study showed — among other things — a “striking” burden of infection among critically ill patients that increased to 51% from the 44.8% seen in the earlier study.

The editorialists also noted that the study found that gram-negative bacterial infections now outnumber gram-positive infections in ICU patients — a “concerning” development because resistance among those organisms is growing and therapeutic options are declining.

The researchers collected demographic, physiological, bacteriological, therapeutic, and outcome data on 14,414 patients, but for this analysis they focused on the 13,796 who were 18 or older.

On the day of the study, the researchers found: 7,087 of the 13,796 adult patients — or 51% — were considered infected. Nearly three-quarters — 9,084 or 71% — were receiving antibiotics either as prophylaxis or treatment. Of the infected patients, 4,503 (64%) had a respiratory infection. Microbiological culture results were positive in 4,947, or 70%, of the infected patients and 62% of the isolates were gram-negative organisms, 47% were gram-positive, and 19% were fungi. The infection rate was 32% for patients who had been in the ICU for one day or less and rose to more than 70% for patients who had been in intensive care for more than seven days, a difference that was significant at P<0.001. The mortality rate of infected patients in the ICU was 25%, compared with 11% for noninfected patients, a difference that was significant at P<0.001. The inhospital mortality rate was also significantly higher, at P<0.001 — 33% versus 15%.

One of the study’s strengths is its international nature, Vincent and colleagues said. But they cautioned against simplistic interpretations across geographic boundaries “because clearly there are large differences in healthcare systems, ICU facilities, and regional policies for infectious disease management.”

Limitations included the voluntary design of the study, which might have introduced a bias, and the lack of data monitoring, which might mean that some definitions were incorrectly interpreted.

Nonetheless, they concluded, the study “demonstrates that infections remain a common problem in ICU patients.”

The researchers did not report any external support for the study or any financial conflicts.

Opal and Calandra reported no conflicts.

BOSTON — In patients with advanced liver disease related to hepatitis C, a course of pegylated interferon and ribavirin (Rebetol) before liver transplant may help them avoid recurrence of infection, a researcher said here.
Nearly 30% of patients receiving the drugs showed no signs of the hepatitis C virus (HCV) three months after receiving a new liver, reported Gregory T. Everson, MD, of the University of Colorado in Denver.
He presented results of a prospective, semirandomized component of a larger study called A2ALL at the American Association for the Study of Liver Diseases meeting.
“This experience supports the concept that pretransplant therapy can prevent allograft reinfection,” he said.

Not surprisingly, the best results were achieved in patients whose HCV viral loads were reduced to undetectable levels at the time of transplant, Everson reported. Among 14 patients in whom this was achieved, eight remained virus free at the post-transplant evaluation.

Duration of the pretreatment regimen was also a significant predictor of post-transplant response, Everson reported.

Some 44% of patients who received the interferon-ribavirin treatment for more than 15 weeks before transplant had a postprocedure response, compared with 18% of those treated for 10 to 15 weeks and 15% of those getting the drugs for less than 10 weeks (P=0.04).

Other factors — such as baseline HCV viremia, viral genotype, type of donor (live versus dead), and toxicity-related dose limitations — were not significantly associated with post-transplant response, although the study may not have been powered adequately to detect such associations.

Of the 79 patients enrolled in the trial, 47 with HCV genotypes 1, 4, 5, or 6 were randomized in a 2:1 ratio to receive the pretransplant drug regimen or no treatment. All of the 32 other patients with HCV genotypes 2 or 3 received the treatment.

The treatment consisted of starting doses of 0.75 mcg/kg/week of pegylated interferon-alfa-2b (PEGIntron) and 600 mg/day of ribavirin, which were both escalated as tolerated over several weeks to standard target levels.

Median treatment duration was 11.4 weeks for the 44 dead-donor candidates and 14.6 weeks for the 35 able to receive live-donor organs.

Transplant was actually performed in 41 patients, 25 of whom were dead-donor candidates.

Everson characterized the effectiveness of the pretransplant drug regimen as “limited.”

He said it should be considered only for selected patients, particularly those with relatively less severe disease.

In the trial, those were the patients who were live-donor candidates along with the dead-donor candidates who received a so-called MELD upgrade because of hepatocellular carcinoma.

“If you take all the patients with HCV going to liver transplant, many of them are too sick to treat with [pegylated interferon] and ribavirin,” he said.

Data from the study indicated that the treatment was significantly toxic. Three-quarters of the treated patients suffered serious adverse events, compared with half of untreated patients (P=0.04). These were seen both before and after transplant.

However, mortality rates were the same in treated and untreated patients, at about 15%.

Everson said it might be possible in the future to try pretreatment in sicker patients when direct antiviral drugs for HCV become available.

In the meantime, he said, patients who can tolerate the treatment need to stay on it for at least 12 weeks.

The study was funded by the National Institutes of Health.

Everson reported relationships with Schering-Plough and Ortho Biotech. Other co-authors reported relationships with Roche, Salix, Gilead, Vertex, Pfizer, GlaxoSmithKline, Amgen, Bayer, Novartis, and Human Genome Sciences, among others.

A leprosy bacterium common to wild armadillos may have spread to humans living in parts of the Southern U.S., investigators reported.

A strain of Mycobacterium leprae isolated from three patients proved to be identical to that obtained from a wild armadillo, and subsequent genotyping of strains from another 33 armadillos and 50 Louisiana clinic outpatients also showed a high degree of correlation, according to Richard W. Truman, PhD, of Louisiana State University in Baton Rouge, and colleagues.

In fact, the same bacterial strain has also been identified from armadillos in five states — a finding consistent with recent acquisition or rapid emergence of the infection, Truman and co-authors reported in the April 28 issue of the New England Journal of Medicine.

“Early diagnosis and prompt drug therapy remain the most effective means to avoid the undesirable complications of leprosy,” concluded Truman, who is also with the Health Resources and Services Administration, and his co-authors.

“Physicians caring for patients with potential exposure to M. leprae by means of armadillos should consider leprosy in their differential diagnosis of chronic cutaneous lesions, especially those not responsive to common treatments,” they wrote.

Leprosy, or Hansen’s disease, remains a rare clinical entity in the U.S., where about 150 new cases are reported annually.

The majority of those affected lived or worked abroad in leprosy-endemic areas and might have acquired the disease while there.

However, about a third of new cases reported in the U.S. involve individuals who report having no foreign residences and appear to have acquired the infection from local sources, the authors wrote in their introduction.

Many of these people, however, do not recall having any contact with a person known to have leprosy.

Most cases of leprosy infection associated with local contact occur in Louisiana and Texas, although sporadic reports of cases in adjacent states suggest possible spreading of endemic involvement, the authors commented.

Surveys have confirmed that armadillos in the Southern U.S. are a large natural reservoir for M. leprae, with a prevalence exceeding 20% in some areas.

Reports of infected armadillos have come from Alabama, Arkansas, Mississippi, and Mexico, in addition to Louisiana and Texas.

Case reports have suggested that armadillos might be a source of M. leprae infection in humans. Moreover, several case-control studies have identified contact with armadillos as a significant risk factor for developing leprosy, the authors wrote.

In an effort to clarify the link between animal and human M. leprae infection, Truman and colleagues performed whole-genome sequencing, single-nucleotide polymorphism (SNP) typing, and variable-number tandem-repeat analysis bacterial strains isolated from armadillos and humans.

Preliminary analyses confirmed that M. leprae strains from a single wild armadillo and three infected outpatients were identical. Those strains were then compared with M. leprae strains from Asia and Brazil, revealing 51 SNPs and an 11-base pair insertion-deletion.

Next, the investigators genotyped and performed 10 variable-number tandem repeats analysis of M. leprae strains obtained from 33 wild armadillos from five states, 50 U.S. outpatients at a clinic in Louisiana, and 64 Venezuelan patients, as well as four foreign reference strains.

The M. leprae genotype of patients with foreign exposure reflected their country of origin or travel.

However, the investigators identified a unique genotype (3I-2-v1) common to 28 of the wild armadillos and among 25 of 39 U.S. patients who lived in areas with possible exposure to armadillo-borne M. leprae.

This genotype has not been reported elsewhere in the world.

“In our study, 3I-2-v1 was the only genotype found in more than two patients,” the authors wrote. “The combination of SNP and variable number tandem repeat genotyping is highly discriminatory and confirms a significant association between the M. leprae strain infecting armadillos and many U.S. patients.

“The 3I-2-v1 strain was significantly associated with a history of residence in areas where M. leprae-infected armadillos have been found (P<0.001).”

The authors had no relevant disclosures.

Vitamin D was significantly lower in people with recurrent transverse myelitis, neuromyelitis optica, and related inflammatory spinal diseases, researchers found.

On the other hand, there appears to be no link between the vitamin and idiopathic transverse myelitis, which does not recur, according to Michael Levy, MD, PhD, of Johns Hopkins University, and colleagues.

The finding, from a retrospective analysis, is reminiscent of what has been seen in multiple sclerosis and other recurrent autoimmune illnesses, and may provide clues to the role vitamin D plays in immune regulation, Levy and colleagues argued online in Archives of Neurology.

Transverse myelitis, with symptoms including back pain and leg weakness, exhibits involvement of the myelin sheath that protects nerve fibers; between 75% and 90% of patients have nonrecurrent disease.

On the other hand, neuromyelitis optica and so-called neuromyelitis spectrum disorders affect the optic nerves and spinal cord and most patients have recurrent, rather than monophasic, disease. Neuromyelitis optica is considered to be a recurrent central nervous system disorder characterized by “longitudinally extensive (transverse myelitis) plus optic neuritis,” the authors noted.

While low levels of vitamin D have been linked to several autoimmune conditions, including multiple sclerosis, the role of the vitamin in transverse myelitis and neuromyelitis optica is not known, the authors noted.

To try to clarify the issue, Levy and colleagues examined records of patients who had 25-hydroxyvitamin D levels taken for clinical reasons at the Johns Hopkins Transverse Myelitis Center and NMO Clinic within the past six years.

Of those, 44 were considered to have nonrecurrent transverse myelitis and were designated the ITM group, and 33 were considered to have recurrent disease and were designated the recurrent TM group.

Analysis showed that total 25-hydroxyvitamin D levels were significantly lower in those in the recurrent TM group, compared with those in the ITM group. Specifically: On average, before adjusting for demographic differences, those in the ITM group had serum 25-hydroxyvitamin D levels of 33 ng/mL compared with 18 ng/mL for those in the recurrent TM group. A level below 20 ng/mL is considered deficient while optimal levels are above 30. After adjustment for age, race, sex, and season during which the sample was taken, the average difference between the groups was attenuated to 10 ng/mL, but was still significant at P=0.002. Women and African Americans were more common in the recurrent TM group.

The analysis suggests, but cannot prove, a link between vitamin D and the recurrent disease, the authors concluded, raising the possibility that supplements might have an effect on the disease course, perhaps reducing the frequency of relapse. But a prospective study is needed to assess that possibility, they argued.

Levy and colleagues cautioned that the study was retrospective, so that some confounding variables might not have been accounted for. As well, they noted, the samples were not taken at the same time in the disease course for each patient. It is possible the disease influences vitamin D levels and vice versa.

The study was supported by the Guthy Jackson Charitable Foundation. Levy reported financial links with ApoPharma and Amplimmune.

OAKLAND, Calif., March 5 — Proteinuria on top of atrial fibrillation increases stroke risk by more than 50%, and that risk also increases steadily as kidney function declines, researchers said.

By itself, atrial fibrillation is a major risk factor for stroke, but when atrial fibrillation patients begin spilling protein into urine, the risk of thromboembolism climbs to 1.54 (95% confidence interval 1.29 to 1.85) after adjustment for known stroke risk factors (prior stroke, age, hypertension, diabetes, and heart failure) and other confounders, said Alan S. Go, M.D., of the division of research at Kaiser Permanente of Northern California.

They reported their findings in the March 17 issue of Circulation, Journal of the American Heart Association.

The link between atrial fibrillation and chronic kidney disease emerged from the ATRIA (Assembly of the Anticoagulation and Risk Factors in Atrial Fibrillation) cohort study of 13,535 adults with nonvalvular atrial fibrillation and no prior kidney transplant.

During follow-up off anticoagulation therapy involving more than 10,000 patients, there were 676 documented ischemic events, including 637 ischemic strokes.

“The rate of thromboembolism off warfarin increased significantly with lower eGFR,” Dr. Go wrote. Moreover, the event rate was “higher with documented proteinuria at every level of estimated glomerular filtration rate.”

Dr. Go and colleagues concluded that clinicians “should consider ascertaining information about the level of estimated glomerular filtration rate and the presence of proteinuria in patients with atrial fibrillation, which may improve the risk stratification for decision-making about the use of antithrombotic therapy for stroke prevention.”

The mean age of patients in the study was 71.6, and 42.8% were women. The patients were treated for atrial fibrillation from July 1, 1996 though December 31, 1997, with follow-up through September 30, 2003.

At baseline, 7,690 patients had estimated glomerular filtration rates of 60 mL or higher, 2,499 had reduced rates — defined as 45 to 59 mL — and 1,338 had rates lower than 45 mL.

Among patients with normal creatinine clearance, 697 (9.1%) had documented proteinuria, as did 382 (15.3%) of those with estimated glomerular filtration rates in the 45 to 59 mL range and 333 (24.9%) of those with rates lower than 45 mL.

There was a graded, increased risk of thromboembolism associated with a lower level of estimated glomerular filtration rate. Compared with a glomerular filtration rate of 60 mL per min per 1.73 m2, the adjusted relative risk for thromboembolism was 1.16 (95% CI, 0.95 to 1.40) for eGFR 45 to 59 mL and 1.39 (95% CI, 1.13 to 1.71) for eGFR

A simple checklist, administered at the one-year well-baby checkup, has the potential to identify children with autism spectrum disorders (ASDs) as early as 12 months — prompting earlier and possibly more effective treatment, researchers reported.
“There is extensive evidence that early therapy can have a positive impact on the developing brain,” remarked lead author Karen Pierce, PhD, of the University of California San Diego.
“The opportunity to diagnose and thus begin treatment for autism around a child’s first birthday has enormous potential to change outcomes for children affected with the disorder,” Piece added in a statement.

A pilot study, conducted among more than 10,000 babies, also demonstrated that it was possible to form a network of pediatricians to use the checklist at the one-year well-baby visit at “virtually no cost,” Pierce and colleagues reported online in the Journal of Pediatrics.

Outside experts said the approach is not entirely new — other such checklists exist — but the project is worth following up, since it may spot autism at an even earlier age than with current practice.

The checklist “is focused in approach and at a relatively young age,” noted Michael Wasserman MD, of Ochsner Medical Center for Children in New Orleans.

An advantage is that the checklist can be filled out by parents or caregivers in five minutes — and scored in less than two by medical staff, the researchers explained.

The downside to the screening approach is a relatively high false-positive rate that may cause anxiety for some parents, Wasserman said in an email to ABC News/MedPage Today.

But false positives commonly occur in many screening methods, Wasserman added. “On balance, this process is worth pursuing,” he said.

In the UCSD pilot study, 137 pediatricians in San Diego County agreed to use the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist (CSBS-DP-IT-Checklist) during the one-year well-baby checkup at their practice.

The 24-item checklist covers three areas: social and emotional communication, receptive and expressive speech, and symbolic behavior, Pierce and colleagues noted.

In essence, the checklist rates a child’s use of eye contact, sounds, words, gestures, object recognition and other forms of communication, compared with age-appropriate norms, the researchers explained.

Infants who failed the screening were referred to the university’s Autism Center of Excellence for further testing and were re-evaluated every six months until age 3.

Of the 10,479 infants who were screened at the one-year well-baby visit, 184 infants failed the screen and were evaluated and tracked, Pierce and colleagues reported.

Of those 184 infants, the researchers said 32 received a provisional or final diagnosis of ASDs, 56 were diagnosed with language delays, nine with developmental delays, and 36 with “other” deficits.

Five infants initially diagnosed with ASDs were found — at an average age of 32 months — to no longer meet criteria for the condition. The remaining 46 infants were false positives.

While those five infants may have been false positives, they also may have benefited from the early intervention, Pierce and colleagues suggested.

All of the toddlers diagnosed with an ASD or developmental delay and 89% of those with language delay were referred for behavioral therapy around 17 months, the investigators reported.

On average, the children started treatment at age 19 months, they added.

In addition, UCSD researchers also surveyed participating pediatricians.

Prior to the study, most of the doctors had not been screening infants systematically for ASDs.

After the study, 96 percent of the pediatricians rated the program positively, and all participating pediatric offices have continued using the screening tool.

Pierce and colleagues cited some important limitations to the study.

For one thing, they cautioned that not all of the infants evaluated by the program have been followed for a full three years — so it remains possible that some diagnoses will change.

As well, the investigators noted that more than 1,000 infants actually failed the screening test, but it was not possible to analyze why only 184 ended up in the evaluation program.

Finally, they said, such a program needs longer evaluation of the children, at least up to school age, “so long-term follow-up of the sample will be important.”

Early identification and treatment for ASDs could “dramatically change the course of a child’s development,” commented Michael Morrier, PhD, of the Emory Autism Center at Atlanta’s Emory University.

The study is an important example of the use of a broadband screening instrument in the general community, Morrier said in an email to ABC News/MedPage Today.

The novel aspect of the study, he said, was that it identified children with ASDs when they were only a year old, “which is significantly younger than most research studies conducted to date.”

“The ‘take home’ message,” he said, “is that community-based pediatricians can be an important aspect of identifying children with possible (autism spectrum disorder) at the earliest ages.”

As well, he said, referrals for diagnosis and treatment “can alter the course of autism in ways that are not possible later on.”

The study was supported by the Organization for Autism Research, Autism Speaks, and the National Institute of Mental Health. The authors declared they had no conflicts of interest.

BUDAPEST — Insulin resistance may accelerate left ventricular hypertrophy in aortic stenosis, and statins appear to worsen the problem, researchers found.
Left ventricular mass index was essentially static among aortic stenosis patients who didn’t already have hypertrophy, but it rose by about 2.5% annually when patients were insulin resistant (P=0.001), Philippe Pibarot, DVM, PhD, of the University of Laval in Quebec, and colleagues reported.
Statin-treated patients fared somewhat worse when insulin resistant, with an annual rate of progression of nearly 3.5% (P=0.003 versus insulin normal on a statin).

Without statin treatment, insulin resistance showed only a trend for left ventricular hypertrophy progression (P=0.09) in the substudy of the ASTRONOMER trial presented here at the European Association of Echocardiography meeting.

“You really have to screen for metabolic syndrome,” including the insulin resistance component, Pibarot urged in an interview with MedPage Today.

Although present in about 25% of the general population, in the older cardiovascular disease population the rate is even higher, he noted.

“It’s an accelerating factor,” Pibarot said. “They may progress faster in terms of valvular stenosis, of also the arterial stiffness, and finally now what we show here in terms of ventricular hypertrophy.”

Exercise and other lifestyle changes should be recommended for such patients, but these insulin-resistant patients may also need valve surgery somewhat earlier than others, he noted.

Prior studies have suggested that patients with metabolic syndrome don’t see the same recovery of left ventricular function after surgery as others do, he explained.

Closer follow-up for screen-positive patients can help identify the optimal time for surgery, he suggested.

That’s especially true because there aren’t any drugs shown to have an impact on ventricular hypertrophy, he noted.

Some evidence suggested statins might be a way to slow aortic stenosis progression, but that wasn’t borne out in the main ASTRONOMER results, with no difference in any diastolic measure after 3.5 years on rosuvastatin (Crestor) versus placebo in mild to moderate aortic stenosis patients.

The same was true in the SEAS trial with ezetimibe/simvastatin (Vytorin).

ASTRONOMER included 269 patients at nearly two dozen Canadian centers with mild to moderate aortic stenosis marked by a peak aortic jet velocity of 2.5 to 4.0 m/s.

During a mean 3.4 years of follow-up, left ventricular mass index didn’t change significantly in those who already had hypertrophy at baseline.

But progression was seen among the 134 with no left ventricular hypertrophy at baseline (P<0.0001), which was faster among the half with insulin resistance marked by a Homeostatic Model Assessment (HOMA) index above 1.24 (P<0.0001 for interaction).

Overall, 46% of insulin resistant patients developed left ventricular hypertrophy during follow-up compared with 10% of those who were not insulin resistant.

Even after full adjustment for other factors, HOMA index independently predicted left ventricular mass index progression rate (P=0.04).

It also correlated with global left ventricular hemodynamic load before and after adjustment for factors including baseline systolic blood pressure, arteriovenous calcification, mean gradient, and statin use (P=0.001 and P=0.003, respectively).

But gender may have been a critical factor to account for as well, cautioned session moderator Genevieve Anne Derumeaux, MD, PhD, of the University of Lyon, France.

Women differ from men in the degree of hypertrophy progression with aging, which may confound the relationship with metabolic syndrome, she explained.

Insulin resistance is “probably important, but we have to weigh it with all confounding factors,” she told MedPage Today.

The study was sponsored by AstraZeneca.

Pibarot reported having no conflicts of interest to disclose.

Derumeaux reported grant support from GE, Philips, and Toshiba.

Switching away from red meat could help women cut down on their heart disease risk, according to a large observational study.
A serving of chicken or turkey to replace one of beef, pork, or lamb would lower coronary heart disease risk 19% (95% confidence interval 3% to 33%), found Adam M. Bernstein, MD, ScD, of Harvard School of Public Health, and colleagues.
Other significant risk-reducing replacements reported online in Circulation: Journal of the American Heart Association included: Nuts, for a 30% reduction (95% CI 17% to 42%) from a one serving per day substitute Fish, for a 24% reduction (95% CI 6% to 39%) from switching one serving daily Low-fat dairy, for a 13% reduction (95% CI 6% to 19%) from one daily serving swap

These results could have a major impact at the population level, Bernstein’s group suggested.

Although the study included only women, the findings would likely apply to men as well, according to Bernstein.

Guidelines from groups like the American Heart Association already support choosing fish, poultry, and meat substitutes or trimmed lean cuts when going for meat.

“Our study helps to support those recommendations,” Bernstein said in an interview. “Really, what we would say is in order to reduce the risk of coronary disease, patients should consider reducing or eliminating red meat from the diet.”

The researchers followed 84,136 women ages 30 to 55 years for 26 years in the Nurses’ Health Study who had no known cancer, diabetes, angina, MI, stroke, or other cardiovascular disease.

Overall, animal protein was associated with increased coronary heart disease risk (P=0.01 for trend), whereas vegetable protein appeared protective (P<0.0001 for trend).

But the types of fat present in these foods appeared to account for the difference as the relationships fell into nonsignificance after controlling for polyunsaturated, monounsaturated, and saturated fat.

After adjusting for age, smoking, and other known cardiovascular risk factors, progressively higher intake of red meat was associated with significantly greater risk of coronary heart disease (P<0.0001), raising risk 29% for the highest intake group that averaged more than two servings a day.

One red or processed meat serving daily was associated with a relative risk of 1.16 compared with none (95% confidence interval 1.09 to 1.23).

The major protein sources looked at in the study correlated only weakly to moderately with fruit and vegetable intake, while egg intake didn’t appear to impact heart risk in any analyses.

When the researchers updated diet based on biennial food questionnaires throughout follow-up, the significant associations with coronary heart disease disappeared for poultry and fish but not for red meat.

“This suggests that other diseases and events do in fact lead nurses to change their diets and thus confound the diet-disease association,” but that the impact of red meat was strongly independent, Bernstein and colleagues wrote in the paper.

They pointed to several risky components of red and processed meats, including heme iron, high saturated fat, and heterocycline amines and advanced glycation end-products created by cooking them.

Nuts, fish, and other healthier protein sources not only lack those components but have other positive ones like fatty acids and polyunsaturated fats that would tend to be protective, the investigators noted.

“The benefit on coronary heart disease risk of such a substitution is thus likely to be due to multiple simultaneous changes in nutrient intake,” they wrote in the paper.

They cautioned that the observational design of the study rendered it impossible to exclude residual and unmeasured confounding, and that dietary information was by self-report.

Strengths of the study included the 26 year follow-up period, good retention of participants, and multiple time points with dietary information.

The study was supported by grants from the National Institutes of Health.

Bernstein reported being supported by a Public Health Service grant from the National Institutes of Health, but no conflicts of interest.

Co-authors reported support from a postdoctoral fellowship by Unilever in one case and an unrestricted research grant from the California Walnut Commission in another.

LITTLE FALLS, N.J., July 22 — Two biotechnology companies in Australia have begun the first human trials of a vaccine for the 2009 H1N1 (swine flu) virus.

This week, Adelaide-based Vaxine Pty Ltd and Melbourne-based CSL Biotherapies injected the first adult volunteers in two separate trials starting days apart.

Now in its winter flu season, Australia has reported about 15,000 confirmed cases of the new H1N1 virus and 41 deaths.

“The demand [for a vaccine] was here yesterday,” Nikolai Petrovsky, MBBS, PhD, Vaxine chairman and research director, told the Associated Press.

Vaccine trials are expected to begin shortly in the U.S. The FDA’s Vaccines and Related Biological Products Advisory Committee will meet tomorrow to discuss clinical trials of an H1N1 vaccine and vaccine approval. (See FDA Lays Framework for Expedited H1N1 Vaccine Approvals)

Vaxine began injecting participants in its 300-person trial on Monday with a synthetic vaccine “based on state-of-the-art recombinant protein technology combined with our proprietary polysaccharide adjuvant system,” Dr. Petrovsky said in a statement.

He said preliminary efficacy data should be available in six to eight weeks.

On Wednesday, CSL Biotherapies began administering vaccine in a 240-person trial that is expected to last seven months. The study is being conducted in partnership with CMAX, a clinical research organization, and Royal Adelaide Hospital, according to a company statement.

All of the participants will receive two injections spaced three weeks apart. Half will receive a standard dose and half will receive a double dose.

“We appreciate that new influenza strains like the ‘swine flu’ can surprise us with properties that mean they might require higher dosing and two injections rather than one to provoke the desired level of immune response in humans,” Russell Basser, MD, CSL’s global director of clinical development, said in a statement.

“CSL will be addressing these questions in the trial to ensure we know the optimum way for the vaccine to be given to protect against this strain of flu,” he said.

John Treanor, MD, a vaccine researcher at the University of Rochester in New York, said “information from this trial will be very useful for all who are working with novel H1N1 vaccines, especially in determining what kind of response to expect with a single dose.”

Rachel David, MD, CSL’s director of public affairs, told ABC News in Australia that a trial involving 400 children ages 6 months to 9 years will begin next month at Women’s and Children’s Hospital in Adelaide.

She also noted that there was no additional safety risk with this vaccine because it is produced in the same manner as seasonal vaccines.

“The substitution of one strain for another in the vaccine is not considered to be a significant change and, from the experience accrued, this is a reasonable presumption,” commented Donald Henderson, MD, MPH, of the University of Pittsburgh and Johns Hopkins.

CSL has received a $180 million order from the U.S. Department for Health and Human Services for bulk antigen.

In addition, the Australian government has ordered 21 million vaccine doses from CSL, enough for the entire population, according to multiple media reports.

This article was developed in collaboration with ABC News.

COX-2 inhibitors, with their improved gastrointestinal toxicity profile, have been marketed since 1999 as safer alternatives to traditional nonsteroidal anti-inflammatory drugs (NSAIDs) in the treatment of arthritis patients.

While achieving unprecedented marketplace acceptance, however, these drugs have remained controversial, with persistent questions surrounding among other issues, their potential cardiovascular toxicity. Vioxx (rofecoxib) was withdrawn from the market for these reasons.

Results of various studies focusing on this issue have, to date, yielded unclear and occasionally conflicting results due to, for example, reliance on different comparator groups and inadequate differentiation between various COX-2 inhibitors, such as Vioxx and Celebrex®(celecoxib). Moreover, previous studies have failed to adequately address the potential cardiovascular risk-modifying effects of concomitant aspirin use.

Although an interim analysis has shown that, after 18 months of use, Vioxx increases the risk for confirmed cardiovascular events, considerable uncertainty remains regarding such matters as the clinical profile of persons at risk for COX-2-mediated cardiovascular events and whether other COX-2-selective agents pose risk similar to that of Vioxx.

To address these unresolved issues, a team of Canadian researchers undertook a retrospective study using a large population of elderly people who had no history of myocardial infarction (MI) and were initiating treatment with an NSAID.

According to a report on the study presented in the latest issue of Annals of Internal Medicine, the researchers aimed toward assessing:

whether and to what extent the use of an NSAID changes the risk for MI compared with patients who did not use an NSAID during the preceding year; and