The Massachusetts anesthesiologist accused of cooking up data for use in trials of pain medications has agreed to plead guilty to criminal charges in a deal with federal prosecutors.

Scott Reuben, who had been among the nation’s most respected investigators on the subject, had been charged with one count of healthcare fraud.

Reuben’s trouble began last year, when an internal audit conducted by Baystate Medical Center in Springfield, Mass., revealed he fabricated data for 21 studies he had conducted during the last 15 years.

The criminal charge had focused on one of these, a trial of Celebrex as part of a “multimodal” pain regimen for knee surgery. The study showed the drug was effective and was published in 2007 in Anesthesia & Analgesia.

“In fact,” the prosecution wrote in a court filing, “Reuben had not enrolled any patients into that study, and the results reported…to Anesthesia & Analgesia were wholly made up by Reuben .”

Had he not copped a plea, Reuben could have spent 10 years behind bars and been fined $250,000. The plea convinced prosecutors to recommend lighter penalties.

After Baystate spilled the beans, journals that had published his tainted articles retracted them.

Baystate terminated its contract with Reuben last spring. At the same time, he reportedly agreed to suspend his practice and was stripped of a professorship at Tufts.

Several widely accepted medical beliefs need to be re-examined in light of the scandal. Topping the list are the effect of COX-2 inhibitors on bone healing and the role of multimodal analgesic regimens in managing chronic pain.

With respect to the former, Reuben’s studies suggested the drugs had no effect on bone fusion, a finding that was contrary to the results of several animal studies.

In the 15 years since cell phones first appeared on the scene, they have spread with astonishing speed and revolutionized communications on a global scale. But right around the time the Motorola Flip-phone was the rage, reports surfaced that cell phone use might be associated with brain cancer.

Since then, the majority of research on the subject has refuted this claim, as has the most recent publication on the matter by Isabelle Deltour of the Danish Cancer Society in Copenhagen, and her colleagues.

Deltour’s group looked at registry data from 4 Scandinavian countries between 1974 an 2003, a period encompassing the birth and growth of the technology.

They found that the incidence of the 2 major forms of brain cancer either remained stable, decreased, or continued the same slow rise that had been observed in the pre-cell phone era.

These findings are “consistent with mobile phone use having no observable effect on brain tumor incidence in this period,” they wrote in the Dec. 16 issue of the Journal of the National Cancer Institute.

The registry contained 59,984 glioma and meningioma cases had been diagnosed in people between the ages of 20 and 79 during the study period.

The incidence of glioma increased in men by 0.5% annually and in women by 0.2% annually during the study.

The incidence of meningioma increased 0.8% per year in men, on average.  In women, the incidence of meningioma rose by 2.9% per year from 1974 to 1987 (when cell phones began hitting the market), then dropped by 2.1% per year between 1987 and 1991, and then began rising again at a rate of 3.8%.

Most of that recent increase in meningioma incidence occurred in women who were at least 60 years old when they were diagnosed–an age group not likely to have been heavy cell-phone users back then.

The scientists could not exclude the possibility that very heavy cell-phone use could pose risks, or that a positive association may be present for very rare brain tumors.

A meta-analysis performed by Italian scientists has shown that reducing salt intake by half in Westernized countries can reduce strokes by 23%, which amounts to about 1.25 million deaths, and reduce cardiovascular disease by 17% which amounts to nearly 3 million additional deaths per year.

Americans consume about 10 grams (or 2 teaspoons) of salt per day.

The  World Health Organization recommends that dietary salt intake should be half that. The US Department of Agriculture recommends just under 6 grams per day.

To reach their astounding conclusions, Pasquale Strazzullo and colleagues at the University of Naples pooled data from 13 prospective studies published between 1966 and 2008. The analysis covered 177,000 subjects who sustained more than 11,000 strokes or cardiovascular events.

The extra power of the meta-analysis proved decisive in reaching the positive conclusions, since only 9 showed a direct positive link between sodium intake and the adverse events (of which only 4 reached statistical significance). Three  actually showed a non-significant inverse relationship.

Studies featuring longer periods of follow-up appeared to strengthen the relationship between salt intake and stroke, although this was not the case for cardiovascular events.

The findings were not impacted by age, sex, and hypertension status.

In an accompanying editorial, Lawrence Appel of Johns Hopkins hailed the study as a “useful and welcome addition” to the confusing literature on the subject.

“At a minimum, Strazzullo and colleagues’ analyses should dispel any residual belief that salt reduction might be harmful (a canard resulting from misinterpretation of studies, often with flawed analyses),” Appel wrote.

Appel probably had in mind long-standing efforts by the food industry to oppose tougher public health policies on dietary salt intake, which have been largely successful because the above-mentioned studies had muddied the waters so completely.

The write-up is in the British Medical Journal.

This post first appeared on HCPLive.com/Psychiatry.

The Food and Drug Administration has sent a letter to 30 companies warning that it hasn’t approved beverages containing both caffeine and alcohol, and that it intends to begin removing such products from store shelves in 30 days if the companies can’t explain why such products are safe and legal.

The letter cited research showing that the combo drinks increase the risk of motor vehicle accidents and sexual assaults.

In one such study, Mary Claire O’Brien of Wake Forest University found that nearly one quarter of all college students claimed to have consumed such beverages in the last month alone.

O’Brien found that students who consumed alcohol-laced energy drinks were 70% more likely to be taken advantage of sexually (6.4% vs. 3.7%) and more than twice as likely (3.7% vs. 1.7%) to have taken sexual advantage of someone than students who drank alcohol alone.

O’Brien reported similarly appalling statistics for riding with a driver that had been drinking (38.9% vs. 22.5%), being hurt or injured (12.3% vs. 5.9%), and requiring medical treatment (2.6% vs. 1.2%). 
 
Last year, state authorities persuaded Anheuser-Busch and MillerCoors to remove their combo drinks, known as Bud Extra, Tilt, and Sparks from the market.

But at least 30 smaller companies still market the drinks, which contain roughly the same dose of caffeine as a large cup of Joe and nearly 10% alcohol. The provocatively-named beverages include Max Vibe, Moon Shot and Slingshot Party Gel.

In its press release on the matter, the FDA cited regulations that deem as unsafe all substances added to food or alcoholic beverages unless their “particular use has been approved by the FDA, or (they are) ‘Generally Recognized As Safe.’”

In a press conference explaining the FDA’s move, Joshua Sharfstein, the agency’s principal deputy commissioner explained that the “FDA is not aware of the basis on which these manufacturers have concluded that caffeine added to alcoholic beverages is, quote, ‘Generally Recognized As Safe.’” (more…)

Physicians have quipped for years that HMG CoA Reductase inhibitors—the cholesterol-busters better known as “statins,” ought to be put in the nation’s drinking water.

After all, they have an excellent safety profile, profoundly beneficial effects on serum cholesterol and cardiovascular mortality, and may even work against sepsis and prostate cancer.

The quip is likely to be heard even more nowadays, because a study by Meredith VanderMeer and colleagues from the Oregon Department of Public Health has shown that patients who were hospitalized for seasonal (not H1N1) flu–and who by coincidence were taking statins–had a lower risk of dying from the infection.

VanderMeer reported her team’s findings at the annual meeting of the Infectious Diseases Society of America.

In their study of 2,800 people hospitalized for flu complications, 801 patients were taking statins for high cholesterol at the time of admission. Only 17 of of them died in the hospital or within 30 days of discharge. In the remaining 1999 patients who were not taking statins, 64 died.

The difference in mortality, 2.1% vs. 3.2%, amounted to a statistically significant 54% reduction, and persisted after controlling for confounding factors such as age and the use of antiviral drugs.

Patients in the study were taking a variety of statins, including Crestor, Lescol, Lipitor, Mevacor, Pravachol, and Zocor. It was not clear whether any one of them was associated with more beneficial effects than the others.

The data for the study was pulled from the CDC’s Emerging Infections Program and covered the 2007-2008 influenza season (again, not H1N1).

According to VanderMeer, the link between statins and decreased seasonal flu mortality is not entirely surprising. Flu complications like pneumonia are caused by inflammation, and statins have anti-inflammatory effects.

VanderMeer suggested that a randomized controlled trial might help confirm her teams’ findings.

In July, 2005, the prestigious Journal of the American Medical Association began requiring that all write-ups of research that had been funded by private sector sources must undergo separate statistical reviews before being accepted for publication.

Oddly, no other first-tier journal followed suit.

Benjamin Djulbegovic of the University of South Florida decided to see whether the unilateral move impacted the types of trials published in top medical peer-reviewed journals. Lo and behold, it did!

In a presentation at last month’s Peer Review Congress, Djulbegovic showed a significant drop the number of industry-funded trials published in JAMA and a coincident increase in such trials that were published in the New England Journal of Medicine and Lancet, the 2 other top-tier journals he studied.

Following Djulbegovic’s presentation, JAMA editor Catherine DeAngelis told an audience of fellow journal editors, “the cynic in me says that if you’re not submitting to JAMA because you have something to hide, so be it. God bless the rest of you for taking those [studies]!”

Djulbegovic reached his conclusion by examining all issues from the 3 journals for the 3 years before, and the 3 years after JAMA enacted its policy.

He found that compared with the preceding period, JAMA published 26% fewer commercially-funded studies after the policy was enacted (63% vs. 37%).

Meanwhile NEJM and Lancet published 12% and 10% more such trials after the JAMA policy went into effect.

The publishing rate for non-commercially funded studies was unchanged in all 3 journals.

Djulbegovic added that if industry-funded trials are simply rerouted from JAMA to another top-tier journal, then the JAMA policy wouldn’t have much impact.

That could only happen if other top-tier journals adopted similar policies.

Just days after a CDC report showed that schools across the nation had drastically reduced on-site sales of calorie-leaden snacks, a new study has revealed that kids have responded by trotting over to nearby convenience stores where they load up on goodies to their hearts’ content.

According to Temple University’s Kelley Borradaile and colleagues, Philadelphia school children spend an average of $1.07 per day on snacks at such corner stores and get 357 calories for their money.

To reach these conclusions, Borradaile’s group surveyed 833 students from 10 urban elementary and middle schools during 2008.

Most of the students were black (54%) or Hispanic/Latino (23%).

More than half (53%) the students in the study reported visiting the convenience store every day. An additional 22% reported doing so 2-4 times per week.

“For the most frequent shoppers, those who shopped both before and after school, five times per week, this would amount to about 712 calories per day, or 3,560 calories per week,” the researchers told MedPageToday.

About 30% of the purchased calories were derived from fat, 66% from carbohydrates and 23% from protein.

Chips were purchased most frequently, accounting for nearly 40% of all purchases. Candy came in second.

According to Borradaile, simply switching from fried to baked chips could reduce the kids’ caloric intake by 14%, and drinking water rather than sugar-laced drinks could cut about 60 calories per store visit.

Alas, the war on childhood obesity is being fought in many theaters. Winning the war requires a concerted effort both inside the schools and out.

The write-up is in Pediatrics.

Contrary to FDA warnings on the matter, a UK  study has found “no clear evidence” to support the claim that the cigarette cessation drug Chantix increases the risk of suicidal thoughts and suicide.

To reach these conclusions, David Gunnell and colleagues at the University of Bristol reviewed the records of 80,660 men and women aged 18-95 years that had received a smoking cessation product (Chantix, Zyban or nicotine replacement therapy) between September 2006 and May 2008.

The scientists found 166 episodes of nonfatal self-harm and 2 suicides — both occurring in patients receiving nicotine replacement therapy. An additional 37 subjects reported having suicidal thoughts.

Chantix and Zyban did increase the risk of such phenomena by 12% and 17% compared with nicotine replacement products in the study, but this difference did not achieve statistical significance. The authors were left to conclude there was no clear evidence that Chantix was associated with an increased risk.

The limited study power “means we cannot rule out either a halving or a twofold increase in risk,” according to the authors.

Chantix also did not appear to increase the risk of depression or suicidal thoughts, confirming a report last March.

The FDA issued black box warnings for both Chantix and Zyban last July, and regulatory agencies around the world followed suit after adverse event reports raised the possibility of such a relationship.

The authors noted that smokers have a nearly threefold increased risk of suicide, probably because people with psychiatric illnesses are far more likely to be smokers.

It’s possible, they said, that smoking “has a beneficial effect on psychiatric symptoms, such as anxiety, that may be lost with smoking cessation.”

The write-up is in the British Medical Journal.

If given the opportunity, most female surgeons would choose the same career again, even though it had a major–and not altogether positive–impact on their lives, according to a study in the Archives of Surgery. 

For the study, Kathrin Troppmann and colleagues from UC Davis mailed surveys to all 3507 surgeons that received certification from the American Board of Surgery in the years 1988, 1992, 1996, 2000 and 2004.

The scientists received 895 responses; 178 from women, and 698 from men.

Although both sexes reported they worked too much, more than 82% of female respondents and 77% of male respondents said they would choose their profession again. More than 75% of the female surgeons and 91% of the male surgeons were married

Female surgeons were less likely to have children (64% vs 91%) than their male counterparts, and tended to have their first child at an older age—after they had entered practice. Men tended to have their first child during residency.

For 27% of female surgeons, the spouse was their child’s primary caretaker. The spouse of male surgeons assumed these responsibilities nearly 80% of the time.

Female surgeons were more than twice as likely to assert that time-off for child-rearing was important after the birth of a child, and that child care should be available at work. Only 9% of females and 3% of males actually took time off after the birth of a child.

“A career in surgery has significant lifestyle implications: the profession is associated with high degrees of patient acuity, significant on-call responsibility, and irregular work hours, all requiring a significant commitment of personal time,” wrote the authors.

They concluded that strategies to increase recruitment and retention of female surgeons should include flexible work schedules and improved maternity leave and child care options.

When Pfizer coughed up $2.3 billion to settle criminal allegations that it promoted off-label use of Bextra, it was the biggest such settlement in history. But Pfizer is not the only drug company to have been nabbed for such activities.

Five years ago, Parke-Davis forked over $430 million to settle a similar suit involving Neurontin.

Now it has come to light that Parke-Davis took advantage of the half-baked policies of certain journals regarding ghostwriting and disclosure of the financial ties of authors to promote off-label utilization of the latter drug.

Between 1997 and 2000, these journals published 13 articles promoting off-label use of Neurontin that were ghostwritten and funded by Parke-Davis without disclosing such arrangements, according to Jenny White, a research analyst at UCSF, who spoke at last months’ Peer Review Congress.

The journals have beefed up their disclosure policies since that time, White added.

To reach these conclusions, White and colleagues reviewed internal industry documents regarding Neurontin that had been archived at her school’s Drug Industry Document Archive. They subsequently asked the journals to delineate current and former policies regarding ghostwriting, conflict of interest and so on.

White’s group identified 24 articles and correspondences with editors that had either been produced with support from grants that Parke-Davis or  by Parke-Davis ghostwriters.

At least 13 of these articles were published in journals that included no disclosure of the fact that Parke-Davis had a role in producing the paper. Only 2 of these articles revealed that the authors had received honoraria from Parke-Davis.

These journals “generally had less stringent requirements [regarding disclosures] than those where articles were not published,” according to White. None of them had a policy regarding disclosure of ghost authorship.

White recommended that peer-reviewed journals adopt uniform policies to prohibit such shenanigans in the future.

The Mediterranean diet may protect against age-related cognitive decline, according to 2 studies published in JAMA.

The diet, which is long on vegetables, fruits, whole grains and fish, and short on red meat and poultry, has already been lauded for its cardio-protective and cancer preventing effects.

The first of the 2 studies, organized by Nikolaos Scarmeas and colleagues at Columbia, showed that the diet and physical activity were independently associated with a reduced risk of Alzheimer’s disease.

Scarmeas’ team enrolled 1,880 older patients with no cognitive impairment at study onset, and performed neuropsychological testing every 18 months for a mean follow-up of 5.4 years.

Alzheimer’s disease was diagnosed in 282 subjects during the study. Subjects who followed the Mediterranean diet were 40% less likely to develop Alzheimer’s than those who did not.

Similarly, a high amount of physical activity, which the scientists defined for this elderly population to be 1.3 hours of vigorous, 2.4 hours of moderate, or 4 hours of light physical activity per week, cut the risk of Alzheimer’s by 33%.

In the second study, Catherine Feart and colleagues at Universite Victor Segalen showed that the Mediterranean diet slowed cognitive decline, though it did not decrease the risk of dementia per se.

In particular, Feart’s team found that those adhering to the diet had fewer errors on the Mini Mental State Examination, but performed no better on 3 other tests of cognition.

In an accompanying editorial, the Mayo Clinic’s David Knopman said the 2 studies “provide moderately compelling evidence that adherence to the Mediterranean-type diet is linked to less late-life cognitive impairment.”

Whether these findings “should be translated into recommendations for the public is the question,” added Knopman. “For now, it is reasonable to nibble on these findings and savor them, but not to swallow them whole.”

Why do you suppose physicians frequently prescribe medications for non-FDA approved uses?

A recent survey has confirmed the worst possible reason ends up causing a lot of it: physicians simply don’t know what the FDA has approved, and what it hasn’t.

That’s the discouraging news from a study designed by G. Caleb Alexander and colleagues from the University of Chicago to characterize physicians’ knowledge of the FDA-approved indications of commonly prescribed drugs.

The scientists found in particular that a nationally representative sample of PCPs and psychiatrists knew the correct FDA-approval status for only 55% of drug-indication pairs.

That dismal performance increased to 60% for drugs actually prescribed by the physicians within the last year.

In the study, physicians were asked to complete a questionnaire focusing on 14 common drug-indication pairs, which varied with respect to FDA-approval status and level of supporting evidence. Subjects were asked to indicate whether each pair had FDA approval.

The drug-indication pairs included valproic acid for bipolar disorder and mania, gabapentin for diabetic neuropathy, Lexapro for panic disorder, trazodone for insomnia, Seroquel for dementia with agitation and Effexor for adjustment disorder.

41% of subjects believed that at least one drug-indication pair with uncertain or no supporting evidence had FDA approval, as is the case for the use of Seroquel in patients having dementia and agitation.

Psychiatrists showed better knowledge of FDA approval status than PCPs (66% vs 42%).

“These results indicate an urgent need for effective methods of disseminating information to physicians about the level of evidence supporting off-label drug uses, with specific attention to common off-label uses known to be ineffective or to carry unacceptable risk of harm,” concluded the authors.

The write-up appears in Pharmacoepidemiology and Drug Safety.

Cursing out loud during a painful experience makes it hurt less, according to scientists at Keele University in Staffordshire, England.

To reach this conclusion, Richard Stephens and colleagues asked 67 undergraduate students to submerge one hand in a bucket of ice water. They instructed half the participants to curse at will during the experience, and told the others to repeat a word that could be used “to describe a table.”

The scientists measured pain tolerance by assessing how long members in each group left their hands in the ice bath. They also tracked pain perception and heart rate following the experience.

The swearing group, it turned out, had significantly increased pain tolerance and heart rate, and lower levels of perceived pain.

“If they swore, they held their hands in cold water for longer,” Stephens told MedPageToday.

The impact of cursing on pain tolerance was the same for men and women, but it caused a larger reduction in perceived pain and a larger bump in heart rate among women.

Stephens’ group concluded the findings might be related to the well-known “fight-or-flight” phenomenon, in which increased release of catecholamines triggers a slew of physiological responses including temporary increase in heart rate, exercise  capacity and so on.

Gail Saltz, a professor of psychiatry at Columbia agreed that the fight-or-flight response can distract people’s attention to a point where they aren’t as cognizant of pain.

“If you’re screaming obscenities, you’re not thinking about your pain,” she told MedPageToday. “The distraction compartmentalizes the other experience.”

Of course, swearing has been a common response to pain for eons. “Many a woman in the delivery room has already figured that out,” Saltz said.

The write-up appears in NeuroReport.

Ever since a 2007 trial of Avandia raised concern that newer generation diabetes-fighters raised cardiovascular risk, sales of the drugs have crashed and investigators have scurried to provide follow-up data one way or the other.

Now, Bristol Meyers Squibb scientists have raised hope that a diabetes drug in the pipeline may actually cut cardiovascular risk.

The drug is saxagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor.

At the ADA meetings last month, Robert Wolf and colleagues reported the results of a meta-analysis, in which they pooled results from 8 phase II and III trials of the drug.

They found major adverse cardiovascular events to be 55% less common in saxagliptin-treated patients than in those receiving either placebo or metformin.

If confirmed with prospective trials, this cardioprotective effect “would be a very important advance,” Wolf told MedPageToday.

The meta-analysis combined 4,607 adverse events reported during 3,758 patient-years of study in 8 randomized, double-blind trials of saxagliptin in type 2 diabetes.

The incidence of major adverse cardiovascular events, which include cardiovascular death, nonfatal MI, and nonfatal stroke was 0.7% in saxagliptin-treated patients and 1.4% in the other groups.

Saxagliptin was found to cut CV risk in high-risk subsets as well. For example, among those with a prior history of cardiovascular disease, the incidence of major adverse CV events was 9.2% in saxagliptin-treated patients versus 46.3% in other groups.

Equally impressive reductions were seen in populations with at least one CV risk factor beyond diabetes, at least 2 risk factors in addition to diabetes, in men, and in those at least 65 years old.

The drug’s codevelopers, BMS and AZ, have submitted an NDA to the FDA, which is expected to rule on the matter later this month.

The millions of folks with no cardiac history who have been diligently popping baby aspirin to prevent future cardiovascular events might as well flush ‘em down the toilet, according to the results of a meta-analysis performed by Oxford University scientists.

In such people, aspirin did reduce the combined risk of heart attack, stroke, and vascular death from 0.57% per year to 0.51%, a significant finding, but it also bumped the risk of gastrointestinal and all extracranial bleeding from 0.07% per year to 0.10%, negating any overall benefit.

Colin Baigent and colleagues oversaw the trial, known as Antithrombotic Trialists’ Collaboration, and published their findings in Lancet.

Current American Heart Association and US Preventive Services Task Force guidelines recommend baby aspirin for primary cardioprevention in those deemed to have a moderately high risk for developing heart disease.

The “current guidelines may need to be reviewed,” Biagent stated matter-of-factly to MedPageToday. For primary prevention, “the main strategies ought to be stopping smoking — if people smoke – and then if further measures are needed, lowering blood pressure, lowering cholesterol.” Baigent added.
 
The scientists had pooled data from 6 randomized, controlled trials of aspirin for the primary prevention of cardiovascular disease. Collectively, the trials had enrolled 95,000 individuals.

Subset analyses involving gender, older age, and a history of either diabetes or high blood pressure revealed nothing to chirp about. In these groups as well, any benefits in cardiovascular risk were offset by increased bleeding.

By the way, Biagent’s group also took a quick peek at secondary prevention, and confirmed that the benefits of aspirin outweigh the risks in individuals with a history of cardiac disease.

Physicians have lamented for decades the absence of a reliable screening test for lung cancer, and they’re going to have to hum that tune awhile longer since the latest study of chest CT confirms previous findings: the test has an unacceptably high false positive rate.

The disappointing findings were reported by the NIH’s Jennifer Croswell at the recently completed meeting of the American Society of Clinical Oncology.

“False-positive results may create increased psychological stress in patients and an increased burden on the healthcare system,” Croswell told MedPageToday.

In Croswell’s blandly named Lung Screening Study, 1,610 participants received a baseline CT and 1,580 got a chest X-ray. Both groups received a repeat imaging study a year hence and were followed for another year.

The scientists defined a positive test as one revealing a noncalcified nodule at least four millimeters in diameter, or any other finding that was suspicious for cancer.

They defined false positives as positive screens that prompted a negative work-up or that resulted in no cancer diagnosis 12 months later.

The false positive rate for participants receiving CT scans was 21% after the first image and 33% after the second.  It was 9% and 15% for those receiving chest x-rays.

In the CT group, false positives tests prompted invasive diagnostic procedures and major surgeries in 6.6% and 1.6% of the participants, respectively. Those numbers were 4.2% and 1.9% for false positives resulting from a chest X-ray.

According to Peter Bach of the Memorial Sloan-Kettering Cancer Center in New York, “nothing really changes here,” as a result of the new study. “There is no organization in the world that recommends screening for lung cancer with CT,” or any other technique, Bach told MedPageToday.