Some of the genetic traits that give bedbugs resistance to insecticides have been pinpointed by U.S. researchers.

The findings will help efforts to understand the biochemical basis for bedbug resistance to insecticides and provide molecular markers for surveillance.

“Different bedbug populations within the U.S. and throughout the world may differ in their levels of resistance and resistance strategies, so there is the need for continuous surveillance,” study author Zach Adelman, an associate professor of entomology with the Vector-Borne Disease Research Group at Virginia Tech, said in a school news release.

There’s been a resurgence of bedbugs in the United States in the past decade, and some bedbugs have developed a resistance to pyrethroids, one of the few classes of insecticides used to control them.

The Virginia Tech team identified three genes (cytochrome P450 monooxygenases, carboxylesterases and glutathione S-transferases) that produce enzymes that can bind to, deactivate and break down two of the most common pyrethroids, deltamethrin and beta-cyfluthrin.

The researchers also discovered that insecticide-resistant bedbugs have a mutation in the sodium channel gene. This mutation gives the bedbugs partial resistance to pyrethroid insecticides.

Highly resistant bedbug populations can have a number of genetic traits that protect them against pyrethroids and possibly other insecticides, the researchers concluded.

The study appears in the Oct. 19 issue of PLoS One.

More information

The U.S. Centers for Disease Control and Prevention has more about bedbugs.

DENVER — Young women with cancer who were counseled about possible reproductive loss and fertility preservation had less regret and better post-treatment quality of life than those who were not counseled, a survey showed.

On a measure of regret regarding the decision to pursue or not pursue fertility preservation, women who were told about the option, visited a specialist, or went through with preservation all had significantly less regret post-treatment (P<0.001), according to Joseph Letourneau, of the University of California San Francisco.

Satisfaction with life post-treatment was significantly higher among women who had their oocytes or embryos frozen (P<0.05), he reported at the American Society for Reproductive Medicine meeting here.

The data emphasize the importance of counseling women of reproductive age about fertility preservation before initiating cancer treatment, he said.

“Cancer patients need to make an informed decision about whether to preserve their fertility in the presence of all available expert information,” he said.

It is known that reproductive loss from cancer treatment can have a detrimental effect on quality of life, Letourneau said, and the American Society of Clinical Oncology recommends discussing fertility preservation with patients of reproductive age.

Previous studies have shown that about 70% of oncologists follow this advice, although fewer than 25% refer patients to fertility specialists. Only about 2% of women ultimately decide to go through with embryo or oocyte cryopreservation.

Letourneau and his colleagues explored the impact of discussing and pursuing fertility conservation on quality of life in women who were included in the California Cancer Registry.

The researchers sent a survey to a random sample of women ages 18 to 40 at the time of their diagnosis from 1993 to 2007. The women had leukemia, Hodgkin’s disease, non-Hodgkin lymphoma, breast, gastrointestinal, or gynecologic cancer.

Of 2,565 women contacted, 1,041 (41%) replied. Reasons for not participating included survey length, having gone through menopause, a lack of interest in having children, or emotional difficulty.

Of the 1,041 women who returned the survey, 918 had had treatment with the potential to compromise fertility — either systemic chemotherapy or pelvic radiation.

Less than two-thirds (61%) of women reported discussing the risk cancer treatment posed to fertility with their oncologist. Another 5% saw a fertility specialist, and 4% underwent fertility preservation.

The researchers used three scales to explore the impact of discussing or pursuing fertility preservation.

On the Decision Regret Scale (scored on a scale of 5 to 25, with higher scores corresponding to more regret), women indicated how much regret they had regarding the decision to pursue — or not pursue — fertility preservation.

Regret was significantly lower in women who reported being counseled about the risk of cancer treatment (10.8 versus 12.6), who visited a fertility specialist (8.5 versus 11.6), and who preserved their fertility (6.5 versus 11.6; P<0.001 for all).

A three-point difference is considered clinically meaningful, Letourneau said.

On the Satisfaction with Life Scale (scored on a scale of 5 to 35, with higher scores corresponding to greater satisfaction), only women who had their oocytes or embryos frozen were significantly more satisfied (23.4 versus 19.9, P<0.05).

The World Health Organization BREF Quality of Life assessment evaluated four domains — physical health, psychological health, social relationships, and environmental health.

Physical health was significantly better in women who had been counseled about the risk of treatment, who visited a specialist, and who went through with preservation (P<0.05).

Psychological health was slightly but significantly improved in women who received counseling from their oncologist, and environmental health was improved in women who visited a specialist and underwent fertility preservation (P<0.05 for all).

Social relationships were not related to counseling or the decision to visit a specialist or pursue fertility preservation.

Letourneau reported that he had no conflicts of interest.

SAN DIEGO — Kids with sickle cell disease frequently show cognitive impairment while they are still toddlers, and before there is evidence of hemodynamic abnormalities or silent strokes, researchers said here.
Prospective evaluations in sickle cell patients beginning at 9 months of age showed neurodevelopment scores that were well below validated norms and were unrelated to socioeconomic status, according to Lori Luchtman-Jones, MD, of Children’s National Medical Center in Washington, D.C.
Also, researchers in Brazil who conducted a prospective case-control study found that middle-school children with sickle cell disease had significantly lower IQ and academic achievement scores, despite showing normal cranial blood velocity and no sign of brain infarcts on MRI exams.

Both studies were presented at the American Society of Hematology’s annual meeting.

Cognitive deficits accompanying sickle cell disease have been noted previously, primarily in older children and teens, as well as in the context of cerebral ischemia and clear hemodynamic abnormalities, such as elevated velocity in transcranial Doppler ultrasound exams.

Clarisse Lobo, MD, of Hemorio in Rio de Janeiro, said her study, which involved 60 children with the SS form of sickle cell disease (mean hemoglobin 8.4 g/dL) and 41 healthy siblings or classmates, was the first to document cognitive impairments in children with normal MRI and ultrasound findings.

Median IQ and achievement scores in the two groups were as follows: Total IQ: 93 in patients, 100 in controls (P=0.03) Executive IQ: 90.9 in patients, 96.5 in controls (P=0.11) Reading achievement: 44 in patients, 56 in controls (P=0.002) Writing achievement: 16 in patients, 22 in controls (P=0.02) Arithmetic achievement: 11 in patients, 15 in controls (P=0.01)

Lobo told MedPage Today that the IQ scores were especially telling because, unlike academic achievement, they would be less influenced by disease-related deficits in schooling.

She also said that, although the statistical analysis did not explicitly account for demographic or socioeconomic status, the fact that controls were siblings or classmates of patients made the two groups highly similar in most respects other than disease status.

Luchtman-Jones, meanwhile, reported preliminary data from an ongoing, prospective study of infants and toddlers in the Washington area with sickle cell disease that is slated to last at least four years.

Data from the first 80 patients, evaluated periodically through 40 months of age, indicate that learning and physical skills as measured in the Bayley Scales of Infant Development are impaired relative to population-based norms, she said.

Scores on the Bayley indexes are standardized to a population-based average of 100 with a standard deviation of 15.

Mean scores in study participants evaluated so far are 84.2 (SD 13.5) for the mental component and 89.1 for motor development (SD 14.4), Luchtman-Jones said.

She pointed out that the standard deviations meant the averages reflected poorer performance for the majority of children and that a few outliers with very low scores pulled down the means all by themselves.

But some children did have very low scores. Fourteen of the 80 children had “significant developmental delay,” defined as more than two standard deviations below the norm for either the motor or mental components.

Moreover, 11 of them were boys. Multivariate analysis indicated that male gender was a significant predictor of impaired mental development scores and that episodes of pneumonia or acute chest syndrome were significantly associated with poorer motor development.

Pain crisis was also linked powerfully with developmental deficits. A diagnosis of significant delay was nine-fold more common among participants who had pain crises, Luchtman-Jones said (odds ratio 9.13, 95% CI 1.77 to 47.10).

Somewhat surprisingly, but consistent with the findings by Lobo and colleagues, socioeconomic status was not a predictor of impaired development.

Among the 38 participants whose mothers were college-educated, 10% had significant development delays.

Another surprise was that the 45 children with the SS form of sickle cell disease showed average impairments similar to those in the 25 with the SC form.

And still another was that none of the children found to have significant delays were receiving special services. Such deficits apparently “can slip under the medical radar,” said Luchtman-Jones, who advised clinicians to be alert to impaired development in sickle cell children.

Zora Rogers, MD, a pediatric hematologist at the University of Texas Southwestern Medical Center in Dallas, told MedPage Today that she was not surprised that cognitive deficits would be apparent before significant overt brain damage has occurred.

“It can’t be good on a simple level to have seven grams of hemoglobin instead of 14 — your brain just can’t work as well,” she said.

Authors of both studies and Rogers declared they had no relevant financial interests.

ATLANTA, Oct. 18 — Older patients are about as likely to be seen in the emergency room for adverse drug events as they are for automobile accidents, according to a CDC study.

Those 65 and older make up a disproportionate percentage of the more than 700,000 patients seen in emergency departments each year because of adverse drug events, reported Daniel S. Budnitz, M.D., M.P.H., of the CDC, and colleagues, in the Oct. 18 issue of the Journal of the American Medical Association.

While the Medicare-age group makes up just 12% of the U.S. population, it accounted for a quarter of adverse drug events overall (25.3%) and half of the adverse events that required hospitalization (48.9%), they found.

Adverse drug events were a slightly more common cause of ED visits than automobile accidents in this age group (177,504 for adverse drug events annually versus about 175,000 for auto accidents).

Only two of the 18 drugs most commonly causing these events have been in clinical use less than two decades. This confirms previous reports that “a large proportion of the public health burden of [adverse drug events] is attributable to ‘older drugs, used poorly.’”

Most conditions caused by adverse drug events were dermatologic, gastrointestinal, or neurological. One third of these were allergic reactions (33.5%, 95% CI 28.6% to 38.4%), and another third were attributed to unintentional overdoses (32.1%, 95% CI 28.6% to 35.7%).

Adverse drug events accounted for 0.6% of all ED visits. The estimated annual population rate of adverse drug events treated in EDs was 2.4 per 1,000 individuals overall (95% CI, 1.7-3.0), but varied by age:

4.3 per 1,000 children younger than five years (95% CI 3.1 to 5.4).
1.0 per 1,000 children ages five to nine years (95% CI 0.7 to 1.3,
2.9 per 1,000 adults ages 60 to 64 (95% CI 1.9 to 3.9).
4.9 per 1,000 adults ages 65 or older (95% CI 2.7 to 7.0).

The rate continued to go up among increasingly older age groups and peaked at 6.8 per 1,000 for adults ages 85 or older (95% CI 3.6 to 10.1).

However, newer drugs do not seem to be the main culprits. Insulins and warfarin, which both typically require ongoing monitoring to prevent overdose or toxicity, caused:

One in every seven estimated adverse drug events treated in EDs (14.1%, 95% confidence interval 9.6% to 18.6%).
More than a quarter of all estimated hospitalizations (871 cases, 95% CI 17.3% to 35.2%).

In the elderly, insulin, warfarin and digoxin were implicated in:

One in every three estimated adverse drug events treated in EDs (1592 cases, 33.3%; 95% CI 27.8% to 38.7%), and
41.5% of estimated hospitalizations (646 cases, 95% CI 32.4% to 50.6%).

The researchers analyzed data from an adverse drug event surveillance program shared by the CDC, the Consumer Product Safety Commission, and the FDA. The surveillance program included 63 hospitals in a nationally representative, stratified probability sample of all hospitals in the United States.

The investigators defined an adverse drug event as an incident ED visit for a condition that the treating physician explicitly attributed to the use of a drug or a drug-specific effect. Adverse events were included whether the therapeutic agent implicated was prescription only, over-the-counter, vaccine, vitamin, dietary supplement, or herbal product. Intentional self-harm, drug therapeutic failures, drug withdrawal, and drug abuse were excluded as were events that occurred as a result of medical treatment during the visit.

The surveillance system did not include data on deaths from adverse drug events.

The researchers found a total of 21,298 adverse drug event cases during 2004 and 2005, which yielded an estimate of 701,547 cases annually (95% CI 509,642 to 893,452). Of these, 16.7% were hospitalized related to adverse drug events (95% CI 13.1% to 20.3%).

Adverse drug events accounted for 2.5% of ED visits due to unintentional injury and 6.7% of unintentional injury hospitalizations. Most emergency department visits for adverse drug events were among women (annual estimate 60.6%, 95% CI 59.1% to 62.1%).

About one in six adverse drug events required hospitalization. The estimated annual population rate of adverse drug events requiring subsequent hospitalization was:

0.4 per 1,000 persons overall (95% CI, 0.2-0.6), but
1.6 per 1,000 for persons aged 65 years or older (95% CI 0.7 to 2.5).

“Historically, the public health burden of adverse events from therapeutic drug use among community-dwelling, non-hospitalized patients has been difficult to estimate, but the problem is large and can be expected to increase,” the investigators wrote.

According to previous studies, about 82% of the U.S. population uses at least one prescription medication, over-the-counter medication, or dietary supplement and 30% use five or more drugs.

The reason why older individuals are more likely to experience adverse drug events may be greater frequency of use and the number of drugs used by this age group, the researchers noted.

The investigators noted that their study likely underestimates the full burden of adverse events since it did not catch those diagnosed and treated in other settings like primary care offices, non-hospital urgent care centers, or direct admission to hospitals. Also, they said the surveillance system could have been biased toward catching acute, well-known drug effects or effects for which testing is available in the emergency department, such as hypoglycemia or hypocoagulability.

Because efforts to reduce outpatient adverse drug events “have been hampered by sparse data,” the findings may help focus prevention efforts, Dr. Budnitz and colleagues wrote.

The study was funded by the CDC, the Consumer Product Safety Commission, and the FDA.

Primary source: Journal of the American Medical Association

Source reference:
Budnitz DS, et al “National Surveillance of Emergency Department Visits for Outpatient Adverse Drug Events” JAMA. 2006;296:1858-1866.

The 2009 pandemic flu virus has marked structural similarities to its 1918 counterpart, two studies have shown — a finding that may help to devise new vaccines.
The two reports may also help clarify the observation that older people were less susceptible to the 2009 pandemic than might have been expected.
“Parts of the 2009 virus are remarkably similar to human H1N1 viruses circulating in the early twentieth century,” said Ian Wilson, DPhil, DSc, of the Scripps Institute in La Jolla, Calif.
With colleagues, Wilson reported online in Science that the hemagglutinin proteins in both viruses share a highly conserved antigenic region, which would suggest the viruses might react to the same antibodies.

“We found a site in common between these that explained that if you had antibodies that could actually recognize this site, you could actually get some neutralization and some protection against the virus,” Wilson said in a Science podcast.

Indeed, tests showed that an antibody to the 1918 flu — isolated from elderly survivors and dubbed 2D1 — also binds to the same region on the 2009 virus, but not to seasonal flu strains, they said.

Meanwhile, in a series of animal experiments, Gary Nabel, MD, PhD, of the National Institute of Allergy and Infectious Diseases in Bethesda, Md., and colleagues developed in vivo evidence to support the theory of crossprotection.

In Science Translational Medicine, they report that mice immunized to the 2009 pandemic strain were also resistant to the 1918 virus and vice versa. But animals immunized to several seasonal flu viruses succumbed quickly to either pandemic strain.
The result is “surprising,” Nabel said in a statement. “We wouldn’t have expected that crossreactive antibodies would be generated against viruses separated by so many years.”
One implication of the finding, both groups said, is that people who were never exposed to the 1918 virus and its close descendants might lack herd immunity to the 2009 strain.
The findings also suggest an evolutionary mechanism that allows influenza to escape the effect of established antibodies — the addition of sugar molecules on the so-called hemagglutinin “spike.”

Neither the 1918 nor the 2009 strain has such molecules, called glycans, according to Nabel and colleagues, but seasonal viruses have between one and three glycans, which mask the antigenic sites where antibodies bind.

Nabel described the glycans as “an umbrella that shields the virus from the immune system.”

He and colleagues engineered mutant forms of both the 1918 and 2009 pandemic viruses so that they had two glycans masking the key antigenic site, dubbed RBD-A.

Mice immunized against the original pandemic viruses were markedly less resistant to the modified strains, they found, although the modified strains could still elicit antibodies to the originals.

Nabel and colleagues argued that the current pandemic strain will probably use that mechanism to develop resistance to the current vaccine as it evolves toward seasonal flu status.

Rational design, they said, might allow the production of a vaccine that could prevent the emergence of such a modified virus, “constraining its evolution into a seasonal influenza and limiting its further spread.”

The Science study was supported by the NIH and the Skaggs Institute for Chemical Biology. Wilson did not report any conflicts.

The Science Translational Medicine study was supported by the National Institute of Allergy and Infectious Diseases. The authors said they had no competing interests.

NEW ORLEANS — Continuous positive airway pressure (CPAP) showed potential to reduce the risk of cardiovascular events and hypertension in nonsleepy patients with obstructive sleep apnea, data from a multicenter randomized trial showed.

Patients treated with CPAP had a 17% lower incidence of cardiovascular events and new-onset hypertension during four years of follow-up. Although the difference did not achieve statistical significance, a per-protocol analysis showed a statistically significant 28% risk reduction with CPAP (P=0.039), according to Ferran Barbe, MD, of Instituto Salud de Carlos III in Madrid.

Patients who were hypertensive at baseline had a 50% reduction in cardiovascular events if they used CPAP for at least four hours each day, Barbe said during a press briefing at the American Thoracic Society meeting.

“We recommend to treat with CPAP patients with sleep apnea that show an apnea-hypopnea index less than 20, regardless of symptoms,” Barbe concluded.

CPAP has demonstrated efficacy for reducing cardiovascular risk in patients with daytime sleepiness associated with obstructive sleep apnea. Whether it confers similar cardiovascular protection in nonsleepy apneic patients was unclear, as the few studies examining the issue failed to show a clear benefit.

To clarify the cardiovascular benefits, Barbe and colleagues at 16 centers in Spain enrolled 710 patients who had an apnea-hypopnea index ≥20 and an Epworth sleepiness score <10; 80% to 85% were men.

All patients underwent a sleep study, blood pressure measurement, and CPAP titration by an automated machine. CPAP adherence was defined as at least four hours’ use daily.

The patients were randomized to CPAP or conservative therapy. They had follow-up visits at three, six, and 12 months and then every 12 months for a total of 48 months of follow-up.

Comparison of baseline characteristics showed a mean age of 55 to 56, body mass index of 31, Epworth score of 6.5, and blood pressure of 131/80 mm Hg. Half the patients were hypertensive at enrollment.

The groups differed significantly only with respect to apnea-hypopnea index, which averaged 46 in the CPAP group and 37 in the control group (P<0.05).

The primary endpoint of the trial was the composite of cardiovascular events and new-onset hypertension. About a fourth of the patients discontinued before the end of the study. In the CPAP group, 81% of patients remained in the study to the end of follow-up compared with 73% in the control arm.

When the study ended, the control group had a cumulative event rate exceeding 40%, which was reduced with CPAP, resulting in an incidence ratio of 0.83 (95% CI 0.63 to 1.1, P=0.195).

An analysis limited to CPAP patients who remained adherent to treatment (at least four hours per day) yielded an incidence ratio of 0.72 (95% CI 0.52 to 0.98).

Considering only the subset of patients who were hypertensive at baseline, the investigators found a 48% reduction in the risk of cardiovascular events in the CPAP group, a nonsignificant difference (P=0.089).

A per-protocol analysis of the same subgroup showed a 53% reduction in the cardiovascular events, which still did not achieve statistical significance (P=0.052).

Barbe said the data showed that one event would be prevented for every 32 nonsleepy patients treated with CPAP.

The study represents a departure from conventional clinical concepts about use of CPAP, said Mary Morrell, PhD, of Imperial College in London, who moderated the press briefing.

“We’ve really been focusing on the sleepiness and treating the cardiovascular risk in patients who we think might have underlying cardiac disease,” said Morrell, who was not involved with the study. “The implications of these data are that we should be thinking more widely about the number of patients that we should treat.”

The prevalence of obstructive sleep apnea without sleepiness is unclear, but estimates range as high as 5% of adults. The condition is almost certainly underdiagnosed, because patients usually come to the attention of clinicians only after a spouse or partner complains of the patient’s snoring or other symptoms, said Barbe.

Barbe reported no disclosures.

PHOENIX — The asthma medication budesonide/formoterol (Symbicort) is safe and effective in African-American patients, according to two studies presented here.

Taken together, the studies suggest that the safety profile of the combination in blacks is similar to that seen in other populations, according to Sheldon Spector, MD, of California Allergy & Asthma Medical Group in Los Angeles, and colleagues.

And these data support using the combination to treat black patients whose asthma is not well controlled using an inhaled corticosteroid such as budesonide alone, Spector and colleagues reported at the annual meeting of the American College of Allergy, Asthma, and Immunology.

Using long-acting beta agonists to treat black patients has been controversial since the 2007 SMART study, which found an excess of respiratory-related deaths among black patients taking salmeterol (Serevent).

The current studies will add to the “comfort” of physicians who would like to prescribe a long-acting beta agonist for black asthma patients but who have been concerned by the result of the SMART study, according to John Oppenheimer, MD, of the New Jersey Medical School in Newark, chairman of the meeting’s program committee.

“This is more evidence that they are safe to use in African Americans,” Oppenheimer told MedPage Today.

The two studies had different patient populations, but both randomly assigned volunteers with moderate-to-severe, persistent asthma to use a pressurized metered dose inhaler containing either budesonide/formoterol or budesonide alone.

Study 1 had several treatment arms, but for this analysis the researchers looked at the 198 nonblack volunteers who were assigned to either budesonide/formoterol or budesonide alone. The efficacy and safety results were compared with data from study 2, in which 308 black adolescents and adults were randomly assigned to either of the two medications.

In both ethnic groups, the researchers found that the combination, compared with the single drug, led to: Significant improvements from baseline in predose one-second forced expiratory volume (FEV1), at P<0.05 Significant improvements from baseline in total daily use of rescue medication, also at P<0.05 No major differences in adverse events, but the percentage of patients with at least one adverse event was lower in Study 2 than in Study 1 Most adverse events were mild to moderate, and headache was the most common

The findings demonstrate the efficacy of the combination medication in two ethnically different populations, the researchers concluded.

Clinicians have been “obviously very concerned about African Americans and long-acting beta agonists,” Oppenheimer told MedPage Today, largely because one result of the SMART study was a black box warning on the labels of the medications.

“This is more evidence that they’re safe to use” despite the warning, Oppenheimer said.

The studies were supported by AstraZeneca. Spector reported financial links with the company as well as with Abbott, Alcon, Genentech, Johnson & Johnson, Novartis, Schering-Plough, Skypharma, Merck, Sepracor, sanofi-aventis, Medpoint, and Boehringer Ingelheim.

Oppenheimer reported financial links with AstraZeneca, GlaxoSmithKline, Merck, Schering-Plough, Novartis, Genentech, and Boehringer Ingelheim.

CHICAGO, Nov. 28 — Ultrasound-guided aspiration and lavage of shoulder calcifications using two 16-gauge needles provides durable functional improvement and relief from pain caused by tendinitis, researchers here reported.In a case series of 2,788 patients treated over a 12-year period, patients achieved a 61% reduction in shoulder pain and improved function by 34.3% compared with baseline, said Luca M. Sconfienza, M.D., of Santa Corona Hospital and the University of Genoa in Genoa, Italy.

The use of two needles rather than one resulted in more complete aspiration of calcium from the shoulder because the aspiration is aided by “constant pressure from the saline infusion in the other needle,” Dr. Sconfienza told attendees at the Radiological Society of North America meeting. “This is an in-and-out approach.”

Moreover, despite the use of 16-gauge needles, “which are about one-third bigger than the needles used in single-needle lavage/aspiration, there were no tendon tears associated with the procedure,” Dr. Sconfienza said.

Dr. Sconfienza and colleagues enrolled the patients, ages 29 to 73, beginning in 1994; 990 were men.

The procedure takes “about 10 minutes,” said co-author Francesca Lacelli, M.D., and patients begin to feel relief 48 hours after the procedure.

Using this technique, all the calcium in the shoulder was removed in 70.1% of procedures. In 23.5%, the calcium was reduced by more than 50%.

Dr. Sconfienza said the procedure was also inexpensive — he estimated the cost of therapy at $98 per procedure. But he said that all patients were referred for physical therapy, which would be an additional cost.

He said, too, that the procedure could also be used to aspirate calcium deposits from other joints — knees and elbows for example. He estimated that 7% to 10% of the general population develops calcium in joints.

Philip O. Alderson, M.D., of Columbia University, who chairs the RSNA communications committee, said that, as a concept, lavage and aspiration is not new, but, he said, the two needle approach was novel.

Dr. Alderson said the procedure is likely to work best when the calcium is contained in a gelatinous matrix, but was probably not effective for removing hardened calcium.

Dr. Lacelli agreed with this observation, but, she added, “the pain of tendinitis usually subsides when calcium hardens,” whereas patients with a “gelatinous matrix” are likely to experience significant pain.

“Our patients were all very symptomatic, which may explain why the procedure was so successful,” she said.

Drs. Sconfienza, Lacelli, and Alderson said they received no research funding, honoraria, or consulting fees from imaging companies or the pharmaceutical industry. The study was investigator initiated and institutionally funded.

Primary source: Radiological Society of North America

Source reference:
Sconfienza LM, et al “Ultrasound (US)-guided percutaneous approach to the therapy of calcific tendinitis of rotator cuff” RSNA Meeting 2007; SST15-09.

GENEVA, July 1 — State-of-the-art diagnostic tests for multidrug-resistant tuberculosis, as well as drugs for treating it, will be made available to certain African and Asian nations under two new programs announced here.

Led by the World Health Organization, the programs will spend $26 million to deploy rapid molecular tests for MDR-TB in 16 countries in Africa and central and south Asia over the next four years.

Another $34 million will go to purchase drugs to treat MDR-TB in those countries and 38 others where the disease is endemic.

The new tests will shorten to two days the time needed to determine whether a given TB strain will respond to standard first-line drugs — rifampicin and isoniazid. Standard culture-based methods now used in developing countries typically require three to four months to yield results.

The PCR-based line probe assays were developed by two European companies, Hain Lifesciences in Germany and Innogenetics in Belgium. The latter’s assay detects rifampicin-resistant TB strains. Hain’s can identify resistance to both drugs.

Both assays are commercially available in Europe and other countries, but not the United States.

In a telephone press conference, Richard O’Brien, M.D., of the Foundation for Innovative New Diagnostics, one of the sponsors of the new initiative, said Hain is now in discussions with the FDA about having its assay approved in the U.S.

Dr. O’Brien said Innogenetics had not expressed interest in FDA approval for its product.

He said that although the new initiative does not directly affect the U.S. or other developed countries, the new tests could improve TB testing there as well.

“Any country that has a possibility of having a patient with MDR-TB should consider using [these tests],” he said.

He added that the American Thoracic Society, the Infectious Disease Society of America, and the CDC are updating their joint TB diagnostic statement to recommend use of rapid molecular tests for MDR-TB.

A WHO committee last month recommended full-scale implementation of the Hain and Innogenetics tests following a successful field trial in South Africa. It showed that the tests were accurate and feasible under real-world conditions in a developing country, the committee’s report said.

The drug-purchase program will focus on currently approved second-line TB drugs known to be effective against MDR-TB, said Salmaan Keshavjee, M.D., of Brigham and Women’s Hospital in Boston. Dr. Keshavjee chairs WHO’s Green Light Committee, which negotiates prices of drugs with producers and develops guidelines for treatment of drug-resistant TB.

Money for both programs will come from UNITAID, an international organization funded by a tax on airline tickets levied by France, Chile, South Korea, and several African nations. Brazil and more than a dozen other countries, mainly in Africa, are expected to follow suit soon.

Neither program will be addressing the growing problem of extensively drug-resistant TB, in which second-line drugs are also ineffective, according to Mario Raviglione, M.D., director of the WHO’s Stop TB Department. An estimated 40,000 cases are now seen worldwide annually.

NICE, France, May 16 — Dipyridamole plus aspirin (Aggrenox) was not proven non-inferior to clopidogrel (Plavix) in prevention of second strokes, nor was there a difference in that regard between telmisartan (Micardis) and placebo, researchers in the PRoFESS trial found.

Results of the highly promoted PRoFESS (Prevention Regimen for Effectively avoiding Second Strokes) trial were reported in a series of presentations at the European Stroke Conference here.

Among the results:

Dipyridamole plus aspirin failed to establish non-inferiority with clopidogrel in preventing second strokes, even though the study found little difference between the drugs in effectiveness.

Telmisartan was unable to prove that it was better than placebo in preventing second strokes.

Neither strategy proved successful in showing better results in improving functional outcomes or cognitive outcomes.

When asked if the researchers were disappointed in the four-year-long trial outcomes, Ralph Sacco, M.D., of the University of Miami and a member of the PRoFESS study group, was philosophical:

“Disappointment is an emotional term, not a scientific one.” He then paused, and said: “Of course, we are disappointed.”

The trial results, which covered several areas of stroke treatment, represented the work of researchers from 695 centers in 35 countries on six continents. They had enrolled 20,332 patients who had been diagnosed with a non-embolic ischemic stroke into the trial sponsored by Boehringer Ingelheim.

Dr. Sacco reported on outcomes involving 10,181 patients who were randomized to receive the dipyridamole regimen and 10,151 who were randomized to receive clopidogrel.

The primary outcome of the trial was to compare the effectiveness of the dipyridamole arm to clopidogrel with a secondary endpoint of effectiveness in preventing other vascular events.

Statistically the trial was designed to determine if dipyridamole was non-inferior to clopidogrel. In fact, the decision of the trialists to seek a very narrow interpretation of non-inferiority prevented them from achieving that goal.

“The trial showed that there were no significant differences in outcomes among stroke patients on either treatment regimen,” Dr. Sacco said, “but nevertheless we were unable to prove non-inferiority. I think the results still indicate that either of these drugs can be used to prevent second strokes.”

He said clinicians will use their clinical judgment and other factors — such as cost — in deciding which drug is best for individual patients.

In the primary outcome, prevention of a second stroke, 916 dipyridamole patients had strokes (9%) compared with 898 clopidogrel patients (8.8%) (P=0.783).

When analyzing the types of strokes, Dr. Sacco said 25 fewer ischemic strokes occurred with the dipyridamole regimen than with clopidogrel; but 38 more hemorrhagic strokes occurred with the dipyridamole regimen. There were more hemorrhages and intracranial bleeding with the dipyridamole regimen than with clopidogrel (P=0.06).

After about 2.5 years, 7.8% of the dipyridamole patients had died compared with 8.1% of the clopidogrel patients, Dr. Sacco said.

The patients were about 66 years old as a group and two-thirds were men; about 75% had high blood pressure and 28% were diabetic; 46% had high cholesterol.

In the part of the study that judged whether immediate treatment of high blood pressure with the angiotensin receptor blocker telmisartan was beneficial compared with placebo, the results again failed to provide a definitive answer.

“The trial indicates that a modest blood pressure lowering of a mean of only 3.5 mm Hg early after a stroke, with treatment given for about 2.5 years, may be of insufficient intensity and duration to reliably evaluate whether blood pressure lowering is of clinical value in post-stroke patients,” said Salim Yusuf, M.D., of McMaster University in Hamilton, Ontario, another of the trial’s researchers.

The researchers assigned 10,146 of the PRoFESS enrollees to receive telmisartan 80 mg a day and 10,186 to receive placebo.

Overall, 8.7% of the patients receiving telmisartan suffered a second stroke in the 2.5-year time frame of the study, Dr. Yusuf said.

About 9.2% of patients receiving placebo also suffered second strokes in the trial, which translated into a 5% reduction with telmisartan, a difference that failed to reach statistical significance (P=0.23).

In a secondary endpoint, major vascular events — cardiovascular death, myocardial infarction, stroke, or new or worsening heart failure — were experienced by 13.5% of patients on telmisartan and 14.4% of patients on placebo (P=0.11).

Dr. Yusuf said that an ad hoc analysis of the study found that during the first six months following the stroke, 3.4% of telmisartan patients and 3.2% of placebo patients suffered a second cerebrovascular event (P=0.38); but in the following two years, the stroke rate was 5.3% for telmisartan and 6% for placebo patients (P=0.029).

“However, I would not refer to this as significant,” he said, “as this was not a pre-specified endpoint.”

“This analysis suggests little early benefit but potential later benefit with telmisartan which increases over time,” Dr. Yusuf explained.

Hans-Christoph Diener, M.D., of the University of Essen in Germany and another of the PRoFESS researchers, said that none of the treatments in the study appeared to improve outcomes on the Mini Mental State Examination, the Barthel Index, or the Modified Rankin Scale — all measures of cognitive or functional status.

“All randomized trials — and there have been at least 90 of these attempts — investigating neuroprotective substances failed in human ischemic stroke,” he said, in explaining the rationale in comparing the treatments in PRoFESS.

However, at the conclusion of the trial he was forced to conclude that “the neuroprotective effects of aspirin or dipyridamole are unlikely. Telmisartan is unlikely to have neuroprotective property.”

On the Barthel Index, about 43.6% of telmisartan patients achieved a 95-100 score — indicating nearly complete recovery in the ability to perform activities of daily living. About 44.5% of patients on placebo achieved a 95-100 Barthel Index score, Dr. Diener said (P=0.731).

On the Barthel Index, about 42.5% of the dipyridamole patients achieved a 95-100 score — indicated nearly complete recovery in the ability to perform activities of daily living. About 45.6% of patients on clopidogrel achieved a 95-100 Barthel Index score, Dr. Diener said (P=0.206).

On the Modified Rankin Scale, about 49.4% of patients on the dipyridamole regimen achieved a score of 0-2, indicating good functional recovery after stroke, compared with 52% of clopidogrel patients (P=0.376).

The findings were similar between telmisartan and placebo and between patients on extended-release fixed-dose dipyridamole and aspirin and those receiving clopidogrel, with no discernable differences in cognitive outcome as measured on the Mini-Mental State Examination.

Dr. Yusuf has disclosed possible financial conflicts with AstraZeneca, sanofi-aventis, Bristol-Myers Squibb, Merck, Organon, Boehringer Ingelheim and Abbott.

Dr. Diener has disclosed possible financial conflicts with Addex Pharma, Allergan, Almirall, AstraZeneca, Bayer, Berlin Chemie, CoLucid, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Gr??nenthal, Janssen-Cilag, Lilly, 3M Medica, Merck Sharp & Dohme, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Roche, Schaper and Br??mmer, sanofi-aventis and Weber & Weber.

Dr. Sacco has disclosed possible financial conflicts with GlaxoSmithKline, Pfizer, Boehringer Ingelheim, sanofi-aventis, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, and Texas Biotechnology.

Primary source: Cerebrovascular Diseases, Vol. 25, Supplement 2, 2008

Source reference:
Diener HJ, et al “Presentation title: Prevention Regimen for Effectively avoiding Second Strokes (PRoFESS) Trial: Cognitive and functional outcomes after stroke”

Sacco R, et al “Presentation title: Prevention Regimen for Effectively avoiding Second Strokes (PRoFESS) Trial: Comparison of a fixed dose combination of extended-release dipyridamole plus asa with clopidogrel”

Yusuf S, et al “Presentation title: Prevention Regimen for Effectively avoiding Second Strokes (PRoFESS) Trial: Telmisartan versus placebo”