Older patients with newly diagnosed myeloma had no loss of efficacy and significantly less toxicity with reduced-intensity induction therapy followed by maintenance, results of a multicenter Spanish study showed.
Two regimens based on less frequent dosing of bortezomib (Velcade) led to major responses in 80% of patients during induction therapy and to complete response rates of about 40% after maintenance therapy, Maria-Victoria Mateos, MD, of University Hospital of Salamanca, and co-authors concluded in an article reported online in The Lancet Oncology.
The incidence of severe neurotoxicity declined by more than 50% and gastrointestinal toxicity by about 80% compared with historical results with twice-weekly dosing, they found.

The combination of melphalan and prednisone has constituted standard therapy for older patients with myeloma for more than 30 years. Clinical trials showed that adding thalidomide or bortezomib improved efficacy compared with the two-drug regimen.

However, studies also have shown that VMP leads to high rates of severe peripheral neurotoxicity and gastrointestinal toxicity. Mateos and co-authors designed a trial aimed at maintaining the efficacy of bortezomib-based treatment and reducing the toxicity.

Investigators at 63 Spanish centers enrolled patients ages 65 and older with newly diagnosed myeloma. All patients received one six-week cycle of bortezomib given twice a week, plus prednisone, and were randomized to either melphalan or thalidomide. The first cycle of therapy was followed by five additional five-week cycles of once-weekly bortezomib, plus prednisone and randomized therapy.

Patients who completed induction therapy were randomized to bortezomib plus either prednisone or thalidomide for as long as three years.

The primary endpoint was response rate during induction and maintenance.

The trial began with 260 patients, 178 of whom completed all six cycles of induction therapy and were randomized to the two induction regimens.

During induction, 81% of patients in the VTP group had partial responses or better, as did 80% of the VMP group. Complete response rates were 28% with VTP and 20% with VMP, a nonsignificant difference.

Combining bortezomib with melphalan and prednisone (VMP) proved safer than the combination of bortezomib, thalidomide, and prednisone (VTP).

VTP was associated with twice as many serious adverse events (31% versus 15%, P=0.01) and a significantly higher discontinuation rate (17% versus 12%, P=0.03).

Grade 3+ toxicity included infection in 1% of VTP patients and 7% of VMP patients, cardiac events (8% versus 0), and peripheral neuropathy (7% versus 9%). Gastrointestinal toxicity occurred in 4% of patients in both groups.

The complete-response rates after maintenance therapy increased to 42% with bortezomib-thalidomide and 39% with bortezomib-prednisone.

Peripheral neuropathy occurred in 2% of the prednisone group and 7% of the thalidomide group. No grade 3+ hematologic toxicity occurred in either group.

Median follow-up was 32 months. The patients had a median progression-free survival of 31 months and a median time to progression of 35 months. The three-year overall survival was 70%. Results were similar in both treatment groups.

“This regimen could represent a platform for further refinement of an optimized treatment of elderly patients with multiple myeloma,” the researchers wrote.

In an accompanying commentary, S. Vincent Rajkumar, MD, of the Mayo Clinic in Rochester, Minn., said the findings have immediate applicability to clinical practice and provide “important answers about how new agents such as bortezomib can be incorporated effectively in the overall treatment strategy.”

At least three other regimens have demonstrated efficacy in randomized trials involving older patients with myeloma, Rajkumar continued. Deciding how to choose among the options will not be simple.

“As exciting as the advances are, we are faced with the challenge of selecting from treatments with significantly different side-effect profiles and route of administration with the benefit of randomized trials,” Rajkumar wrote.

“For now, the choice of a particular regimen in elderly patients with myeloma will need to be made by baseline comorbidities, cytogenetic risk factors, drug availability, and physician preference.”

Mateos disclosed relationships with Millennium, Celgene, Ortho-Biotech. Several co-authors disclosed multiple relationships with commercial interests.

Rajkumar reported that he had no relevant disclosures.

BALTIMORE, Sept. 28 — Patients with rheumatoid arthritis who meditated were measurably less stressed after six months than those given standard care, but the disease was no better, said investigators here.

An analysis of the effects of a mindfulness-based stress reduction program in RA patients showed that those who used the technique had both significantly lower psychological distress and a higher sense of well-being than controls, found Elizabeth K. Pradhan, M.P.H., Ph.D., of the University of Maryland, and colleagues.

There were also trends towards lower depressive symptoms scores and enhanced mindfulness among the patients who meditated, but the practice had no effect on the severity of RA, the authors reported in the October issue of Arthritis & Rheumatism — Arthritis Care & Research.

“For doctors wishing to offer patients a complement to medical management, mindfulness meditation may offer hope for improving psychological distress and strengthening well-being in patients with RA,” they wrote.

The mindfulness-based stress reduction program was developed as a meditation training program developed by Jon Kabat-Zinn, Ph.D., of the University of Massachusetts Medical School in Worcester, and colleagues.

The program defines “mindfulness” as “moment-to-moment nonjudgmental attention and awareness actively cultivated and developed through meditation.”

Similar in philosophy to cognitive behavioral therapy, mindfulness-based stress reduction “teaches participants to notice and relate differently to thoughts and emotions, with a sense of compassion for self and others underlying the endeavor,” the authors wrote. “By continually bringing the mind back to the present moment, mindfulness meditation is thought to increase clarity, calmness, and well-being.”

In both descriptive and controlled studies, the technique has been linked to improvement of psychological symptoms in patients with anxiety disorders, fibromyalgia, chronic pain, cancer, and multiple sclerosis, and has been shown to reduce relapse among patients in remission from major depressive disorder, they noted.

In this pilot study 31 patients with RA were randomly assigned to mindfulness training for eight weeks followed by a four-month maintenance period, and 32 were put on a waitlist for training and received standard care, and were offered the mindfulness training free of charge at the study’s end.

All patients received standard care from their rheumatologists during the study. The outcomes measures included responses to self-reported items on the Symptom Checklist-90-R, looking at depressive symptoms, psychological distress, well-being and mindfulness.

Arthritis severity was measured by the Disease Activity Score in 28 joints (DAS28) by a physician masked to treatment status. The authors estimated adjusted means and mean changes in outcomes in mixed-model repeated measures analyses.

They found that there were no statistically different outcomes between those who meditated and controls at two months, but at six months the patients who underwent the mindfulness training and practiced meditation had significantly less psychological stress than controls (P=0.04) and had significantly greater well being (P=0.03).

Patients in the meditation group had a 35% greater reduction in psychological distress from baseline than did controls. The meditating patients also had nonsignificant trends towards lower depressive symptom scores (P=0.08) and more mindfulness (P=0.09).

There was no effect of the intervention on DAS28 scores, however, the authors noted.

The authors acknowledged that the study had limitations including the small sample size and a patient sample with a relatively high socioeconomic status, suggesting more social support and coping mechanisms than other patients with rheumatoid arthritis might have.

The study was supported by the National Institute for Complementary and Alternative Medicine. Co-author Trish Magyari, M.S., teaches mindfulness-based stress reduction. No other conflicts of interest were reported.

Primary source: Arthritis & Rheumatism — Arthritis Care & Research

Source reference:

Pradhan EK et al. “Effect of Mindfulness-Based Stress Reduction in Rheumatoid Arthritis Patients.” Arthrits Rheum 2007; 57(7): 1134-1142.

GOLDEN, Colo., July 30 — Practice makes better bariatric surgery, with fewer complications and quicker hospital stays, according to investigators here.

A survey of more than 166,000 bariatric surgery procedures performed in 19 states over three years showed that patients treated at the most experienced hospitals had 64% fewer complications and 26% shorter stays than similar patients treated in low-volume centers, found Samantha Collier, M.D., and colleagues, of HealthGrades, a healthcare ratings company.

“Assuming all hospitals in the 19 states studied could perform at the level of the top-performing hospitals 5,902 patients could have potentially avoided one or more major in-hospital complications associated with bariatric surgery,” they wrote, in a report titled Bariatric Surgery Trends in American Hospitals.

The authors found that from 2003 through 2005, 166,410 bariatric surgery procedures were performed in the 19 states, and that only about 1,300 more procedures were performed in 2005 than in 2003.

A total of 731 hospitals performed at least one bariatric surgery procedure during the years of the study, but only 481 had sufficient volume to merit a rating, as determined by a minimum 30 cases across three years of data and at least five cases in the most current year.

They also found that 70% of the procedures in 2005 were laparoscopic rather than open gastric bypass, and that the laparoscopic method, as might be expected, was associated with fewer in-hospital complications.

The authors also ranked the hospitals with one, three, or five stars, with five star representing those institutions with significantly better performance than predicted by multivariate logistic regression. Three stars represented average performance, not statistically different from that predicted, and one star was awarded to those hospitals with significantly worse than predicted outcomes.

Of the 481 centers studied, 109 (22.7%) earned five stars, 257 hospitals (53.4%) were given three, and 15 (23.9%) just one.

They found that the five-star rated hospitals performed almost twice the number of procedures as one-star rated hospitals (533 versus 293), and that a typical patient undergoing a bariatric surgery procedure in one of the highest-ranked hospitals would have, on average, a 64% lower risk of one or more major in-hospital complications compared with a low-ranking center.

Compared with all one- and three-star centers, patients treated in a five-star center had a 41% lower risk for complications. The most frequent complications were surgical complications of the respiratory system, occurring in 1.45% of all patients, gastrointestinal system problems in 1.28% post-operative pulmonary insufficiency in 1.19%, hemorrhage complicating the procedure in 1.14%, and accidental operative laceration in 1.08%.

“Two hundred and fifty patients died in hospital from complications of bariatric surgery during the study period,” the authors wrote. “The average U.S. mortality rate during the study period was 0.15%, or 1.5 patients per 1,000. While the absolute overall mortality rate was low for most hospitals, the mortality rate in five-star rated hospitals was almost half the rate of all other U.S. hospitals.”

They also found that average length of stay among bariatric surgery patients was 26% shorter for those treated in the top-echelon hospitals compared with those treated in one-star centers.

Individual hospital quality results from this study are available at www.healthgrades.

“Bariatric surgery has been demonstrated to be highly effective for those with morbid obesity, but the relatively new procedures are not yet regulated or a credentialed surgical subspecialty,” said Dr. Collier. “So it is important that patients considering surgery know how hospitals rate.”

The authors noted several study limitations, including the possibility that the cases may have been coded incorrectly or incompletely by the hospital, and that there could be missing, incorrect, or outdated data.

The study was funded by HealthGrades, a publicly traded firm. The authors are employees of the company.

Primary source: Health Grades

Source reference:
Collier S et al. “The Second Annual HealthGrades Bariatric Surgery Trends in American Hospitals Study July 2007.”

Researchers said that the average patient randomized to TMC114/r — no matter which dose was given in the Phase II trial — was able to reduce viral load by more than 90% and in many cases patients were able to reduce the viral load to undetectable levels, a marker of disease control.

The trial was designed to treat experienced patients, on regimens that were failing to control disease due to major mutations that were making protease inhibitors ineffective.

“We saw almost a 2log10 drop in HIV among patients receiving the 600 mg twice a day dose of TMC114,” said Richard Haubrich, MD, associate adjunct professor of medicine at the University of California, San Diego, who presented the planned 24-week interim report on the drug being developed by Tibotec, Mechelen, Belgium.

The group on TMC114 was compared with a control group of patients who were placed on the best available protease inhibitor regimen by their clinicians. Those patients achieved a 0.27log10 decline. “The difference was highly significant reaching a P

The quiet world of nuclear medicine is about to get a lot quieter — not for lack of work, but because of a looming shortage of radioisotopes.

Much of nuclear medicine depends on a steady supply of an isotope called molybdenum-99, a byproduct of nuclear fission. The molybdenum is packed into so-called “generators” and, over about a two-week period, each generator delivers a supply of another radioactive substance, technetium-99m.

The technetium-99m is used in more than 16 million nuclear imaging procedures every year in the U.S. alone for, among other things, sentinel node biopsies in cancer surgery, bone scans, and staging cancer patients.

But the main source of supply for North America — the NRU reactor in Chalk River, Ontario — has been shut down since last May and isn’t expected back online until April at the earliest. (See Canadian Reactor Shutdown Slows Nuclear Medicine)

Meanwhile, one of the reactors that has been picking up the slack — the Petten facility in the Netherlands — is to shut down this week for six months of maintenance.

So far, clinicians have been “getting by,” according to Robert Atcher, PhD, of the University of New Mexico, who is past president of the Society of Nuclear Medicine and chairman of its isotope committee.

But doctors aren’t looking forward to the next month or so. They’ll have to make do with even less, and patient care — not badly affected so far — will be at risk in some cases, experts said.

Reactors Too Old, Too Few

The root of the problem is the age of the machines used to make isotopes. All five reactors are 40 to 50 years old and need increasing amounts of time-consuming and costly maintenance.

The shortages also showcase a critical gap in the supply chain — the U.S. has no domestic reactor that can make the isotopes and one is not likely to be up and running for several years.

Since last May, clinicians have rescheduled procedures as much as possible and many facilities have started using a radioactive variant of thallium, which went out of favor about 15 years ago because technetium-99m has better imaging characteristics, Atcher told MedPage Today.

But there’s a limit to how much rescheduling can be done, he said. “These patients are ill — in many cases these aren’t really elective procedures,” Atcher said.

While most radioisotopes are used for imaging, some are used in therapy, Atcher said. And, in a twist he said surprised him, some of those isotopes — including iodine-131 — are also now in short supply.

Iodine-131 is made using processes similar to those used for molybdenum/technetium, but demand is much smaller, so that experts didn’t think the reactor shutdown would have a noticeable effect, he said.

But in late 2009, Atcher said, physicians were finding it hard to get their hands on the substance, which is used to treat thyroid cancer, Graves’ disease, and hyperthyroidism.

“These are patients who need treatment who are now being rescheduled and delayed, because we have a shortage of the iodine,” Atcher said.

Reactors in Belgium, France, and South Africa have been “rescheduling and rejuggling” production to cover the time when Petten is offline and the Canadian reactor is not yet back on line, Atcher said.

One estimate, he said, is that production will be at between 30% and 40% of normal.

“So we’ll be able to squeak by,” Atcher said.

That said, “there will be shortages,” according to Steve Littlejohn, vice president of communications for Covidien, one of the two major suppliers of isotopes.

Since May, Littlejohn told MedPage Today, the company has been able to fill its standing orders, because the other reactors added production cycles to fill the gap left by the Canadian machine.

But it will be tough to fill those orders once the Dutch facility shuts down, he said. To add to the problem, there will be a short period in mid-March when none of the reactors will be working.

Bill Dawes, vice president for manufacturing and supply chain at Lantheus Medical Imaging, reported the same general picture — meeting targets until now, but with a tough few weeks ahead.

“We expect the month of March will be challenging for the global community,” he told MedPage Today.

How Doctors Are Coping

Clinicians have adopted a range of strategies over the past few months, trying to use the available isotopes frugally.

In Houston, institutions have tried a good neighbor policy, ensuring that all have at least some technetium-99m, according to Eric Rohren, MD, PhD, interim chief of nuclear medicine at M.D. Anderson Cancer Center.

Because of that, he told MedPage Today, “we’ve not had a day when we absolutely could not get isotopes.”

At M.D. Anderson, he added, he and his colleagues have been decreasing by about 15% to 20% the radiation dose they use for such things as bone scans — a measure that extends the available isotope.

The danger is, he said, “if you back off too far, eventually it’s going to have an impact on image quality” and patient care.

Rohren added, “it may come to a point where we are truly facing a crisis — I think it’s more of a when, not if, to be honest.”

There are alternatives for many procedures, he noted, including CT and PET scanning, using radioisotopes that aren’t made in nuclear reactors. Radioactive thalium-201 and nitrogen-13 ammonia can be used for cardiac imaging. Magnetic resonance imaging can fill in some other gaps.

All of those have drawbacks — increased cost, greater radiation burden, or lower image quality.

And for some procedures — such as hepatobiliary scanning for suspected gall bladder disease — there’s simply no alternative. In such cases, a lack of technetium-99m “really will have an impact on patient care,” he said.

On the other side of the country, “we’re faring pretty well, considering,” according to Allegra Bruce, a nuclear pharmacist at Boston’s Massachusetts General Hospital.

The facility usually uses two technetium-99m generators a week and has been able to get just one a week for the past several months from its main supplier, filling in the gaps with occasional supply from the other company.

Because of that, she told MedPage Today, the facility is able to operate at 100% of its usual capacity two days a week and 80% on the other three days.

But unlike M.D. Anderson, she said, clinicians at her institution are still administering the full radiation dose called for in protocols. “The generators that we do have, we’re working harder,” he said.

And, like the Houston institution, Massachusetts General is using alternatives such as thallium in order to extend the available technetium-99m, she said.

Most of those strategies are also being employed in Chicago, according to Daniel Appelbaum, MD, director of nuclear medicine at the University of Chicago Medical Center.

But the impending Petten shutdown has Appelbaum and colleagues looking forward with trepidation. “We’re certainly nervous about it,” he told MedPage Today.

With the current shortage, deliveries of technetium-99m have been delayed by a day or so, and some patients could be rescheduled if necessary. But if the delays between shipments grow, he said, “suddenly you can’t push things off for 24 hours.”

Chicago has also tried to use other tests and modalities, he said, but as the shortages grow “there will be situations when the nuclear medicine test is really the only thing of benefit for the patients and we simply can’t provide it.”

It could be “a scary situation,” Appelbaum said.

The nuclear medicine society and a coalition of other professional groups involved in the issue last summer urged Congress to take steps to ensure a domestic supply.

The groups argued that an existing reactor at the University of Missouri could meet half the domestic demand with little change, while a collaborative effort to build a new machine (involving Covidien and its partner Babcock & Wilcox) could supply the rest.

The U.S. Department of Energy has awarded $9 million to the latter project and GE-Hitachi has also been awarded $2.25 million to develop isotope production facilities.

ROCHESTER, N.Y., Nov. 6 — Abdominal obesity in America’s children has increased by more than 60% since 1988 through 1994, apparently thanks to supersized fast food, TV, and video games, according to researchers here.

So it appeared from comparative National Health and Nutrition Surveys (NHANES) data, reported Stephen Cook, M.D., of the University of Rochester (N.Y.) Medical Center in the Nov. 5 issue of Pediatrics.

Using waist circumference as a surrogate marker, they found that the most recent data, taken in 2003-2004, showed the prevalence of abdominal obesity had increased among boys by 65.4% (from 10.5% to 17.4%) and among girls by 69.4% (from 10.5% to 17.8%) since the 1988-1994 NHANES survey. Both increases were statistically significant at P

SALT LAKE CITY, June 20 — Americans aren’t having nightmares—or dreams of any kind—that replay the 9/11 attack on New York, according to sleep researchers.

That is not to say that Americans are ignoring 9/11 in their dreams, said psychiatrist Ernest Hartmann, M.D., of Tufts, in Boston. Instead, the 9/11 event has had the effect of increasing the intensity of imagery in dreams that superficially have nothing to do with airplane attacks on downtown New York.

The intensity of the so-called “central image” of a dream is correlated with the strength of the emotions that underlie the dream, Dr. Hartmann said at Sleep 2006, the joint meeting of the Sleep Research Society and the American Academy of Sleep Medicine.

The example he gave was that after 9/11 the tidal wave that sweeps one away in a dream is more intense than it was before 9/11. On the other hand, it remains a tidal wave—not a replay of a TV image of an airplane attack on a building.

Dr. Hartmann and colleagues have performed a range of studies, showing that concept of dream imagery. In one study, for instance, he and colleagues showed that students who reported earlier physical or sexual abuse tended to have dreams whose central image was much more intense than students without such a traumatic history.

But such studies are not systematic, he said, in that they do not involve a common event. “We tried to do a systematic study, using the events of 9/11, which presumably produced at last some signs of trauma in all of us,” Dr. Hartmann said.

The researchers found 44 people—60% of them female—who have routinely recorded their dreams for years and asked them to submit the records of the last 10 dreams before the 9/11 attacks and the first 10 dreams afterward. The ages of the respondents ranged from 25 to 69.

Dr. Hartmann and colleagues analyzed the reports, on a blinded basis, scoring each of the 880 dreams for intensity of central image, the emotion pictured by the central image, its length, its dreamlike quality, and its vividness. They also looked for three elements of content—attacks, buildings like the World Trade Center or the Pentagon, and airplanes—and applied a scale of “nightmare-likeness.”

The key finding, he said, was that 36 of the 44 participants had an increase in central image intensity—scored on a scale ranging from 0 to 3—after the attacks. Before 9/11, the 44 participants had an average intensity of 1.10, while afterward, it rose to 1.28, a difference that was significant at P<0.001.

There was no difference in length, dreamlike-ness, or vividness, he said, or in dreams involving buildings or airplanes. On the other hand, there was an increase in dreams involving attacks of all kinds, which was significant at P<0.01, and a marginally significant increase in nightmare quality (P<0.05).

What was missing, Dr. Hartmann said, were any direct “replays” of the events. “We all saw those airplanes hit the towers hundred of times,” he said. “That never showed up in the dreams.”

The study is a “very good first step in looking at how events that are very significant for a very broad segment of the population” become translated into dreams, said Anne Germain, Ph.D., of the University of Pittsburgh, who chaired the session in which Dr. Hartmann reported his study.

She noted in an interview that a great deal of research has been done on how daytime events affect dreams, but Dr. Hartmann’s study differs because it uses a single common event. “9/11 has the particularity that it touched a lot of people at once,” she said. “The question is, did it influence dreams in people in general who all shared this one particular event.”

And what the study appears to show, she said, is that there was at least some influence: “You don’t get replays of images, but you do get replays of emotions.”

Men who smoke the longest have the lowest risk of needing a total joint replacement, researchers found.
After accounting for potential confounders, those who had smoked for 48 years or more had a 42% to 51% lower risk of total knee or hip replacement than men who had never smoked, depending on age, according to George Mnatzaganian, a doctoral student at the University of Adelaide in Australia, and colleagues.
Accounting for the competing risk of death, which was higher in the heavier smokers, did not change the association, the researchers reported online in Arthritis & Rheumatism.

They noted that this is the first study to demonstrate a strong, inverse, dose-response relationship between the duration of smoking and the risk of total joint replacement.

“More research is needed to better understand the role of smoking in the pathogenesis of osteoarthritis,” they wrote.

Mnatzaganian and his colleagues examined predictors of total joint replacement — with a focus on body weight, physical activity levels, and smoking — using data from the Health in Men Study (HIMS), a randomized trial of ultrasound screening for abdominal aortic aneurysm in men ages 65 to 83 living in Perth, Australia.

The current analysis included 11,388 men (mean age 72.1) who provided detailed health information at baseline from 1996 to 1999 and were followed through 2007. They were divided into three age groups — 65 to 69, 70 to 74, and 75 and older.

During follow-up, 7.5% had a total joint replacement with more than half (59.5%) involving the knee and the rest involving the hip.

Smoking was associated with a lower risk of total joint replacement in a dose-response fashion in all three age groups (P≤0.05 for the trends).

After adjustment for socioeconomic status, height, weight, physical activity levels, and comorbidities, men who smoked the longest — 48 or more years — were significantly less likely to undergo total joint replacement than those who had never smoked, with hazard ratios of 0.49, 0.58, and 0.51 for the increasing age groups.

Heavier smokers had higher mortality rates, but even after accounting for that, smoking was still associated with a lower risk of total joint replacements.

Although the observational findings cannot establish a causal relationship, the researchers noted that there is some evidence that smoking may directly reduce the severity of osteoarthritis, pointing to an in vitro study that showed an association between nicotine and stimulation of the anabolic activity of the chondrocytes.

But there are other possible explanations for the finding, including an underestimation of comorbidities, which could have overestimated the risk of joint replacement among men who had never smoked; possible confounding by unmeasured factors; and selection biases prior to surgery.

In addition to smoking, being overweight was also a predictor of total joint replacement, with the risk increasing along with body weight in all three age groups (P<0.001 for all).

For example, the heaviest men (those who weighed 193 pounds or more) were more than four times as likely to undergo total joint replacement as men who weighed less than 150 pounds (HR 4.36, 95% CI 2.58 to 7.36).

The association between weight and joint replacement was stronger for the knee than for the hip, “suggesting a biomechanical component in the relationship between body weight and osteoarthritis,” according to the researchers.

“However,” they wrote, “more studies are showing a positive relationship between being overweight and osteoarthritis at different body sites including knee and hip, and non-weight bearing joints such as small joints of the hands, suggesting a connection between osteoarthritis and metabolically active adipose tissue.”

Mnatzaganian and his colleagues acknowledged some limitations of the study, including the lack of direct evaluations of osteoarthritis status among the participants; possible misclassification of socioeconomic status; the use of self-reported physical activity levels; and the collection of patient characteristics at baseline only.

The study was funded by the University of Adelaide.

The authors did not make any other financial disclosures.

Hypertension in childhood may be a sign of abnormal growth and accelerated maturation in other body systems as well, researchers said.

Elevated blood pressure was linked to bone growth unexpectedly mature for a child’s age, Mieczyslaw Litwin, MD, PhD, of the Children’s Memorial Health Institute in Warsaw, Poland, and colleagues found.

Bone age was 1.9 years older than chronological age in children with primary hypertension (P<0.0001) whereas the two ages corresponded in kids with normal blood pressure, they reported in the December issue of Hypertension: Journal of the American Heart Association.

Although measuring skeletal maturation may not be practical in clinical practice, the results suggest that accelerated biological maturation — independent of sexual maturation — is characteristic of hypertension in children and adolescents, the researchers wrote.

The findings provide yet another line of evidence that a healthy diet and exercise — strategies known to alter the tempo of biological maturation — may prevent problems later in life from early onset of hypertension, they said.

Although traits like hypertension and overweight in childhood predict adult cardiovascular health, the problem has been deciding when to start intervening, commented Giuseppe Mancia, MD, PhD, of the University of Milan-Bicocca in Milan, Italy.

Physiological changes associated with childhood hypertension are already present to some degree at an early stage of life, and waiting to treat until adulthood makes some of the changes irreversible, Mancia said in a statement on behalf of the European Society of Cardiology.

“So there are grounds for earlier intervention,” he said. “Serious implementation of lifestyle changes, such as weight control and exercise, appears justified.”

Litwin’s group studied 54 consecutive children (average age 14) with newly diagnosed, treatment-naive primary hypertension seen at a single center from 2007 through 2009. These children had been diagnosed during routine school checkups or clinical workup for other complaints.

They were compared with the same number of age-, sex- and body mass index-matched healthy children with normal blood pressure who had participated in a cross-sectional, school-based study.

Dual energy x-ray absorptiometry (DXA) scans showed little difference between bone age and chronological age in normotensive controls (14.7 versus 14.2, P=NS).

But among those with hypertension, bone age averaged 16.0 compared with a chronological age average of 14.1, which was significant in both girls and boys (P<0.001 and P<0.0001, respectively) and across BMI groups (P<0.01 to P<0.0001).

Bone maturity was linked to hypertension with an apparent dose effect for the difference from chronological age: 0.45 in normotensive children 1.59 in prehypertensive children 1.77 in children with stage 1 hypertension 2.38 in children with stage 2 hypertension

Likewise, accelerated skeletal maturation was more common in hypertensive than normotensive kids (88.9% versus 37.0%, P<0.0001) whereas the opposite was true for delayed skeletal maturation (0.0% versus 5.6%).

Bone age appeared to be an even stronger predictor of hypertension than height or chronological age.

The researchers cautioned that the study relied on standards of skeletal maturation that were developed based on a population born in the 1950s and ’60s.

Although rapid improvement of socioeconomic conditions in Poland since that time may have influenced discrepancies between bone age and chronological age, the reference standard was the same for both groups in the study, they noted.

The study was also limited by ambulatory blood pressure monitoring only in hypertensive children and possible lack of generalizability to diverse populations.

The investigators acknowledged that bone maturation studies are currently not practical in ambulatory pediatric practice and thus the clinical relevance of the study is unclear.

The study was funded by internal grants from the Children’s Memorial Health Institute.

The researchers reported no conflicts of interest.

Drug users who inject themselves with methamphetamine are 80 percent more likely to attempt suicide than those abusing other drugs, new research reveals.

The magnified risk for meth users is probably rooted in a mixture of social, structural and neurobiological factors, say researchers from Columbia University’s Mailman School of Public Health in New York City and the University of British Columbia in Vancouver, Canada.

“Compared to other injection drug users, it is possible that methamphetamine users are more isolated and have poorer social support systems,” study author and Mailman postdoctoral fellow Brandon Marshall said in a Columbia news release.

Marshall and his colleagues report their findings in the December issue of Drug and Alcohol Dependence.

The team used material from interviews involving nearly 1,900 men and women that were conducted in the Vancouver area over seven years, from 2001 to 2008. The authors note that Vancouver’s downtown eastside district is well known as a center for illegal drug use.

“This is one of North America’s largest cohorts of injection drug users, and the research is among the first longitudinal studies to examine attempts of suicide by injection drug users,” Marshall (who is also a research coordinator for the Urban Health Research Initiative in British Colombia) said in the release.

A little more than a third of the participants were women, and another third were of Aboriginal descent. All responded to questions regarding their drug use, treatment experience and risky behaviors with respect to HIV. All told, 8 percent were found to have previously attempted suicide.

The authors found that meth injection was linked to a greater risk for suicide attempts across the board. That is, even infrequent meth users bore an elevated risk for attempting suicide, while those who frequently injected meth faced the highest such risk.

“The high rate of attempted suicide observed in this study suggests that suicide prevention efforts should be an integral part of substance abuse treatment programs,” Marshall said. “In addition, people who inject methamphetamine but are not in treatment would likely benefit from improved suicide risk assessment and other mental health support services within health care settings.”

The study was funded by both the U.S. National Institutes of Health and the Canadian Institutes of Health Research.

More information

For more on methamphetamine, visit the U.S. National Institute on Drug Abuse.