Latest Research

August 17, 2007

A summary of the "must-read" articles from the journals in that pile on your desk.

Marijuana Associated With Higher Psychosis Risk

Risk increases with more frequent use

Marijuana use is associated with about a 40 percent increase in the risk of psychosis, with the risk increasing with more frequent use, according to a study in the July 28 issue of The Lancet.

Stanley Zammit, Ph.D., from Cardiff University in the United Kingdom, and colleagues performed a meta-analysis of 35 longitudinal and population-based studies published through September 2006, examining cannabis use and the risk of psychotic or affective mental health outcomes.

The researchers found that the risk of psychosis was higher in people who had ever used cannabis (adjusted odds ratio, 1.41), with the risk increasing with increasing frequency of cannabis use (adjusted odds ratio, 2.09). The effect of cannabis use on depression, suicidal thoughts, and anxiety were less clear.

"In the public debate, cannabis has been considered a more or less harmless drug compared with alcohol, central stimulants, and opioids," Merete Nordentoft, M.D., Ph.D., M.P.H., and Carsten Hjorthoj from Copenhagen University Hospital in Denmark noted in an accompanying editorial.

"However, the potential long-term hazardous effects of cannabis with regard to psychosis seem to have been overlooked, and there is a need to warn the public of these dangers, as well as to establish treatment to help young frequent cannabis users," Nordentoft and Hjorthoj write.

AbstractFull Text (subscription or payment may be required)Editorial

Nursing, Other Occupations Linked to Adult Asthma

Risk higher after inhalation accidents

A substantial number of adult asthma cases are due to occupational exposure, particularly in nursing, or inhalation accidents such as fire or chemical spills, according to a study in the July 28 issue of The Lancet.

Josep M. Anto, M.D., from the Municipal Institute of Medical Research in Barcelona, Spain, and colleagues examined the risk of new-onset asthma in 6,837 adults in 13 countries based on occupation, work-related exposures, and inhalation accidents.

The researchers found a significantly higher risk of asthma in those exposed to substances known to cause occupational asthma (relative risk, 1.6), nurses (relative risk, 2.2), and those exposed to acute inhalation events such as fire, mixing cleaning products, or chemical spills. Occupational exposures accounted for a population-attributable risk of asthma of 10 percent to 25 percent, or 250 to 300 cases per million people per year, the authors estimated.

The study "is a welcome contribution that provides a better estimate of the frequency of asthma attributable to occupational agents," Jean-Luc Malo, M.D., and Denyse Gautrin, Ph.D., from Sacre-Coeur Hospital in Montreal, Quebec, Canada, wrote in an accompanying editorial.

AbstractFull Text (subscription or payment may be required)Editorial

Chemotherapy, Stem Cells Beneficial in Testicular Cancer

Even as third-line therapy, high-dose chemotherapy plus stem cell rescue may cure metastatic germ cell testicular cancer

Metastatic testicular germ cell tumors may be curable with high-dose chemotherapy plus hematopoietic stem cell rescue, according to a report in the July 26 issue of the New England Journal of Medicine.

Lawrence H. Einhorn, M.D., of the Indiana University Cancer Center in Indianapolis, and colleagues examined the efficacy of high-dose chemotherapy plus hematopoietic stem cell rescue in 184 patients with cisplatin-resistant, progressively growing testicular cancer.

Of these patients, 173 received two consecutive courses of high-dose chemotherapy for three days followed by an infusion of autologous peripheral-blood hematopoietic stem cells after each chemotherapy treatment. The other 11 patients received a single course of the treatment.

During a median follow-up of 48 months, 63 percent of the 184 patients were continually disease-free. Of these, 90 percent were disease-free for more than two years. Moreover, 18 of 40 patients with progressive metastatic disease and tumors that were refractory to platinum remained disease-free for a median of 49 months and 22 of 49 patients who received high-dose chemotherapy as third-line or later treatment remained disease-free for a median of 46 months. There were a total of three drug-related deaths occurring during therapy. Three patients developed acute leukemia after therapy.

"Testicular tumors are potentially curable by means of high-dose chemotherapy plus hematopoietic stem cell rescue, even when this regimen is used as third-line or later therapy or in patients with platinum-refractory disease," the researchers conclude.

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Polar Expedition Can Cause Mental Highs and Lows

Expeditions bring positive and negative psychological effects

Polar expeditions can have both positive and negative effects on the psyche, according to a study published in the July 26 issue of The Lancet.

Lawrence A. Palinkas, Ph.D., of the University of Southern California, Los Angeles, and Peter Suedfeld, Ph.D., of the University of British Columbia in Vancouver, British Columbia, Canada, conducted a literature review on the psychological effects of polar expeditions which included treks and stays at summer camps or year-round research stations.

Due to long periods of isolation and confinement and the extreme physical surroundings, polar expeditioners may report sleep disruption, memory loss, difficulty concentrating, reduced alertness, depression and interpersonal tension with team members. Specifically, one study included in the analysis showed that 88 percent of men and 77 percent of women had sleep problems lasting for at least two weeks. Polar expeditioners do, however, experience salutogenic effects as a result of successfully coping with stress, enhanced self-sufficiency, improvements in health and personal growth.

"Continued research in the psychological effects of polar expeditions is important, because it helps us to better understand some of the underlying principles of behavior in isolated and confined environments," the study authors concluded.

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Interleukin-7 Receptor Gene Linked to Multiple Sclerosis

Interleukin-7 receptor variants increase risk, though not as much as HLA region of immune system

An international team of researchers has discovered that variants of the interleukin-7 receptor α (IL7Rα) gene increase the risk of multiple sclerosis. The findings were published online July 29 in two studies in Nature Genetics and confirmed in a third, which was released early by the New England Journal of Medicine.

In the first study, Jonathan L. Haines, Ph.D., from Vanderbilt University Medical Center in Nashville, Tenn., and colleagues examined three genes with links to multiple sclerosis in 760 families of European descent, with 1,055 individuals with multiple sclerosis. They identified a single nucleotide polymorphism in the transmembrane region of the IL7Rα chain, which was confirmed in several independent populations.

In the second study, Jan Hillert, M.D., Ph.D., from the Karolinska Institutet in Stockholm, Sweden, and colleagues confirmed a previous association of three single nucleotide polymorphisms in the IL7Rα gene in 1,820 individuals with multiple sclerosis and 2,634 healthy individuals from Nordic countries. Multiple sclerosis patients had higher expression of IL7Rα as well as IL7 in their cerebrospinal fluid (but not blood) compared with individuals with other non-inflammatory neurological diseases.

In the study in the New England Journal of Medicine, Jonathan L. Haines, Ph.D., from Vanderbilt University Medical Center in Nashville, Tenn., and colleagues performed a genome-wide association study of single nucleotide polymorphisms associated with multiple sclerosis in 931 families with a child with multiple sclerosis. They found that two single nucleotide polymorphisms in the interleukin-2 receptor α IL2Rα) gene, one in the IL7Rα gene, and several in the HLA-DRA locus were strongly associated with multiple sclerosis.

"It is important to recognize that the increased risk contributed by IL2RA and IL7Rα is very low and that these two alleles explain only a very small proportion of the variance (0.2 percent) in the risk of multiple sclerosis," Leena Peltonen, M.D., Ph.D., from the University of Helsinki, Finland, wrote in an accompanying editorial in the New England Journal of Medicine. "The HLA region retains its unique position as the only known major risk gene for multiple sclerosis."

Abstract - HainesFull Text (subscription or payment may be required)Abstract - HillertFull Text (subscription or payment may be required)

Abstract - NEJMFull TextEditorial - NEJM

Health Risks Higher for Assisted Reproduction

Much of higher risk due to health risks of being infertile

Although the health risks for mother and child are higher for assisted reproduction than spontaneous conception, much of this is related to the underlying health risks of being infertile, according to a review of singleton pregnancies in the July 28 issue of The Lancet. Children born after assisted reproduction appear to develop normally with normal family relationships.

Alastair G. Sutcliffe, M.D., from University College London in the United Kingdom, and Michael Ludwig, M.D., from Endokrinologikum in Hamburg, Germany, reviewed the risks of assisted reproduction by searching the published medical literature and abstracts from 1980-2005, including 3,980 articles.

Couples undergoing intracytoplasmic sperm injection have a higher risk of sex chromosome abnormalities, possibly due to the high percentage of abnormal sperm in these couples. The risk of pregnancy complications are higher, including a 55 percent higher risk of pre-eclampsia, a twofold higher risk of preterm delivery, and a threefold higher risk of placenta previa.

The risk of major malformations is about 30 percent higher. Children born after assisted reproduction have a higher risk of developing cerebral palsy, which is reduced if single embryo transfer is used. Infants who are neurodevelopmentally mature at birth progress normally, and there are no concerns about family relationships and psychosocial issues after assisted reproduction.

"Some of the risks to children born after assisted reproductive technologies do not arise as a result of the techniques but from the background biology of the subfertile couple," Sutcliffe and Ludwig wrote. "Child development seems to be normal, and no adverse psychosocial effects are apparent for families who have undergone the sometimes stressful procedures involved."

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Religious Physicians Not More Likely to Work With Poor

But some spiritual, religious factors may be associated with caring for underserved populations

Physicians who consider themselves religious are no more likely to provide care for underserved patient populations than those who do not, according to a survey in the July/August issue of the Annals of Family Medicine.

Farr Curlin, M.D., of the University of Chicago, and colleagues analyzed data from 1,144 U.S. physicians who responded to a self-administered questionnaire that measured their religious and spiritual characteristics and some of their motivations for practicing medicine.

Twenty-six percent of respondents reported that they considered their patient populations underserved. The authors found that physicians who were more generally religious -- as measured by their self-reported intrinsic religiosity or attendance at religious services -- weren't more likely to practice among the underserved. However, factors that were associated with greater likelihood of caring for the underserved included self-identification as "highly spiritual" (odds ratio, 1.7) and strongly agreeing that their religious beliefs influenced their practice of medicine (odds ratio, 1.6).

More research is needed to ascertain the factors that lead some physicians to focus on underserved populations, the authors wrote. However, with such knowledge, "Medical school admissions officials could increase the supply of physicians who care for the underserved by giving preference to candidates who possess characteristics known to predict a disposition toward such work," the authors wrote.

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Antibiotics in Children Favor Development of Resistance

A prescription doubles resistance elements found in H. influenza compared with no antibiotic

Children who are prescribed amoxicillin for acute respiratory infection are twice as likely to carry resistant organisms at 2-week follow-up compared to those who do not receive antibiotics, according to a study published online July 26 in BMJ.

Angela Chung, M.D., of the University of Oxford in Oxford, U.K., and colleagues followed 119 children with acute respiratory infection, including 71 who received a beta lactam antibiotic. They tested H. influenza isolates from throat swabs taken at 2 weeks and at 12 weeks for mean minimum inhibitory concentration (MIC) for ampicillin and the presence of the ICEHin1056 resistance element.

Compared to children who received no antibiotic, amoxicillin prescriptions were associated with threefold greater MIC for ampicillin (9.2 μg/mL versus 2.7 μg/mL) and twice as many isolates with the ICEHin1056 resistance element (67 percent versus 36 percent, relative risk 1.9) at 2-week follow-up. At 12-week follow-up, both measures had returned almost to baseline.

"The short term effect of amoxicillin prescribed in primary care is transitory in the individual child but sufficient to sustain a high level of antibiotic resistance in the population," concluded the authors.

AbstractFull Text

Child Abuse in Military More Likely During Deployments

Increased stress for parent at home may play a role

Among families of enlisted soldiers in the U.S. Army, the rates of child maltreatment and neglect are higher during combat-related deployments than in other duties, according to a study in the Aug. 1 issue of Journal of the American Medical Association.

Deborah A. Gibbs, M.S.P.H., of RTI International in Research Triangle Park, N.C., and colleagues evaluated the impact that combat-related deployments have on the rates of child maltreatment. They examined 1,771 families of enlisted U.S. Army soldiers who had at least one substantiated report of child maltreatment during the study period.

The rate of maltreatment was 42 percent higher during periods of deployment compared to nondeployment. The rate of moderate to severe child maltreatment was more than 60 percent greater during deployment, and the rate of child neglect was nearly twice as high during deployment. However, the rate of physical abuse was lower during deployment (relative risk, 0.76).

Researchers postulated that increased stress experienced by the parent remaining at home may explain these findings. "The greater rate of child maltreatment associated with deployments suggests the need for enhanced support for civilian parents in terms of additional resources, more effective services, development of services that those parents at greatest risk will be likely to seek out and accept, and greater outreach to connect parents to services, " wrote the authors.

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Patient Referral Compliance Increases With Doctors' Help

Most who fail to keep specialist visits say they don't have time or feel their problems are resolved

A high rate of patients complete specialist referrals when their primary care physician uses the simple low-cost strategy of scheduling the appointments for them, according to a study published in the July/August issue of Annals of Family Medicine.

Christopher B. Forrest, M.D., Ph.D., of the University of Pennsylvania, Philadelphia, and colleagues sent questionnaires to 1,022 patients with a mean age of 48.2 years, referred by 133 physicians in 81 practices located in 30 states to determine compliance rates. Most referrals were made for therapeutic procedures and diagnostic tests, and almost half of the patients had a 5-year or longer relationship with their physician.

Researchers found that about 8 in 10 referrals took place within three months, based on survey responses from 776 patients whose physicians then determined their completion status. The most common reasons given by patients for not completing specialist care were a belief their health problems had been resolved (47 percent), "not enough time" (37.3 percent), and a disagreement with their physician over the need for a referral (26.5 percent). Insurers denied 2.3 percent of the referrals, with most of the denials coming from Medicaid plans.

"Findings from this study suggest that referral completion rates may be increased by assisting patients with scheduling their specialty appointments and promoting continuity of care," the authors wrote. They noted that physicians scheduled specialty care for 78.8 percent of referrals made and sent specialists relevant patient information for 85.3 percent of the cases.

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Echocardiography Detects More Rheumatic Heart Disease

Prevalence 10 times higher than by clinical examination

Echocardiography screening detected about 10 times more cases of rheumatic heart disease in children in Cambodia and Mozambique than clinical examinations, according to a study in the Aug. 2 issue of the New England Journal of Medicine.

Eloi Marijon, M.D., from the Georges Pompidou European Hospital in Paris, and colleagues examined the prevalence of rheumatic heart disease by clinical examination and echocardiography in 3,677 children in Cambodia and 2,170 children in Mozambique (all 6 to 17 years old).

The researchers found that clinical examination followed by echocardiographic confirmation gave a rheumatic heart disease prevalence of 2.2 cases per 1,000 in Cambodia and 2.3 cases per 1,000 in Mozambique. In contrast, echocardiographic screening gave a prevalence of 21.5 cases per 1,000 in Cambodia and 30.4 cases per 1,000 in Mozambique. Most cases in both countries involved the mitral valve, the authors noted.

"Systemic screening with echocardiography, as compared with clinical screening, reveals a much higher prevalence of rheumatic heart disease (approximately 10 times as great)," Marijon and colleagues concluded.

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Gene Linked to Sporadic Amyotrophic Lateral Sclerosis

Variations in FLJ10986 may increase risk for developing sporadic amyotrophic lateral sclerosis

Variations in a previously uncharacterized gene called FLJ10986 may increase the risk for developing sporadic amyotrophic lateral sclerosis, according to a new genome-wide analysis published early online Aug. 1 in the New England Journal of Medicine.

Travis Dunckley, Ph.D., of the Translational Genomics Research Institute in Phoenix, and colleagues performed a genome-wide association analysis using 766,955 single-nucleotide polymorphisms (SNPs) identified in 386 white patients with sporadic amyotrophic lateral sclerosis and 542 neurologically healthy controls. They then confirmed the associations found in this series in two additional analyses.

They identified 10 genetic loci that were significantly associated with sporadic amyotrophic lateral sclerosis in the three series of patients. Another 41 loci showed significant associations in two of the three series. Overall, the most significant association was found for a SNP near FLJ10986 on chromosome 1. Patients were more likely to have this genotype than controls (odds ratio 1.35). They concluded that variations in FLJ10986 may confer genetic susceptibility to sporadic ALS.

"Perhaps this pathway, if validated in other studies, could lead to a new approach to treatment of ALS," wrote Richard W. Orrell, M.D., of the University College London, U.K., in an accompanying editorial.

AbstractFull TextEditorial

Progesterone Prevents Preterm Birth in Some Women

Effective in women with short cervix, ineffective in women pregnant with twins

Progesterone is effective in preventing premature birth in women with a short cervix but ineffective in preventing premature birth in women pregnant with twins, according to two studies in the Aug. 2 issue of the New England Journal of Medicine.

In the first study, Kypros H. Nicolaides, M.D., from King's College Hospital Medical School in London, and colleagues randomly assigned 413 pregnant women with a cervix less than 15 mm long to 200 mg vaginal progesterone per night or placebo from 24 weeks to 34 weeks of gestation. They found that progesterone treatment significantly reduced the risk of spontaneous delivery before 34 weeks gestation (relative risk 0.56) and tended to reduce the risk of neonatal morbidity (relative risk 0.59).

In the second study, Dwight J. Rouse, M.D., from the University of Alabama in Birmingham, and colleagues randomly assigned 665 women pregnant with twins to intramuscular injections with 17 alpha-hydroxyprogesterone caproate or placebo starting at 16 weeks to 20 weeks gestation to 35 weeks. They found that the risk of delivery or fetal death before 35 weeks and the risk of serious adverse neonatal events were similar in both groups (relative risk 1.1 for both).

"Even if progesterone therapy is effective for some women who are at risk of preterm labor, reliable evidence is needed about long-term effects on the children before it could be widely recommended," Jim G. Thornton, M.D., from the University of Nottingham in the United Kingdom wrote in an accompanying editorial.

Abstract - RouseFull TextAbstract - NicolaidesFull TextEditorial

Strategy Reduces High Rate of Caesarean Deliveries

Induction strategy may provide an alternative to Caesarean delivery

Practitioners show high rates of successful vaginal births with prostaglandin-assisted preventive labor induction, which for many women may be a safe alternative to Caesarean deliveries, according to a study published in the July/August issue of Annals of Family Medicine.

James Nicholson, M.D., M.S.C.E., of the University of Pennsylvania Health System, Philadelphia, and colleagues did a four-year retrospective study of 1,869 women at a rural New England hospital to determine the success of an Active Management of Risk in Pregnancy at Term (AMOR-IPAT) program in reducing the rate of Caesarean deliveries from 1993-1997. The strategy used pregnancy dating and risk scoring to estimate an optimal time of delivery and started labor induction with cervical ripening, if needed, to promote safe vaginal births.

Researchers found that 5.3 percent of women exposed to the AMOR-IPAT strategy by their physicians wound up having Caesarean deliveries compared to 11.8 percent of Caesarean deliveries by women receiving more traditional provider care.

"At a time when national Caesarean delivery rates have surpassed 30 percent, when preventive primary Caesarean delivery is being offered as an unproven means of preventing intrapartum perineal trauma, and when the short- and long-term complications of Caesarean delivery are still not completely understood, we hope that practitioners might consider the potential benefits of an apparently safe alternative method of maternity care that is associated with high rates of successful vaginal delivery," the authors wrote.

An accompanying editorial by Michael Klein of the Children's and Women's Health Centre of British Columbia in Vancouver, Canada, disputes whether the AMOR-IPAT approach makes any significant difference in lowering the rate of Caesarean sections. "If childbirth were simple, a simple intervention such as preventive induction might do the job. Unfortunately, childbirth is not simple, and neither is the proposed intervention," Klein wrote.

The pilot of this study was funded in 2000 by Forest Pharmaceuticals, which also supplied its dinoprostone vaginal insert cervical ripening product for use in clinical trials.

AbstractFull Text Editorial

Early Use of Interferon Beneficial in Multiple Sclerosis

Using interferon beta-1b may prevent disability if treatment starts early

Initiating the use of interferon beta-1b soon after a suspected diagnosis of relapsing-remitting multiple sclerosis can help prevent progression to clinically definite multiple sclerosis as well as disability, according to research published in the Aug. 4 issue of The Lancet.

Ludwig Kappos, M.D., of the University Hospital Petersgraben in Basel, Switzerland, and colleagues report on the three-year follow-up of the Betaferon/Betaseron in Newly Emerging Multiple Sclerosis for Initial Treatment (BENEFIT) study. Overall, 292 patients with a first multiple sclerosis event and at least two clinically silent lesions were randomized to receive 250 μg of interferon beta-1b while 176 were given placebo every other day for two years or until diagnosis of clinically definite multiple sclerosis.

This was followed by an open-label interferon beta-1b phase, which 418 (89 percent of the original group) entered and 392 (84 percent) completed through three years of follow-up.

Early initiation of interferon beta-1b reduced the risk of clinically definite multiple sclerosis by 41 percent; 85 patients (51 percent) in the delayed group progressed to this stage compared with 99 (37 percent) in the early treatment group. The risk of disability was reduced by 40 percent.

"Our data suggest that early initiation of treatment with interferon beta-1b prevents the development of confirmed disability, supporting its use after the first manifestation of relapsing-remitting multiple sclerosis," the authors conclude.

AbstractFull Text (subscription or payment may be required)Editorial

Screening for Atrial Fibrillation Increases Detection Rate

Pulse-taking followed by electrocardiography preferred

Active screening of elderly individuals for atrial fibrillation in primary care increases the detection rate, with pulse-taking followed by electrocardiography being the preferred method, according to study findings published online Aug. 3 in BMJ.

F.D. Richard Hobbs, M.B.Ch.B., from the University of Birmingham in the United Kingdom, and colleagues randomly assigned 14,802 patients aged 65 years or older at 50 primary care centers in England to three groups: no screening; systematic screening for atrial fibrillation by invitation for electrocardiography; or opportunistic screening, in which patients with an irregular pulse were invited to undergo electrocardiography.

The researchers found that screening increased the detection rate for new cases of atrial fibrillation (1.63 versus 1.04 percent per year). Systemic and opportunistic screening were similarly effective in detecting new cases (1.62 versus 1.64 percent).

"Active screening for atrial fibrillation detects additional cases over current practice," Hobbs and colleagues conclude. "The preferred method of screening in patients aged 65 or over in primary care is opportunistic pulse-taking with follow-up electrocardiography."

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U.S. Abstinence Programs Ineffective for HIV Prevention

Analysis of 13 trials suggests they have no effect on self-reported sexual behavior

Abstinence-only programs in the United States have no effect on the risk of HIV infection based on self-reported sexual behavior, according to a systematic review of 13 trials published online Aug. 3 in BMJ.

Kristen Underhill, M.Sc., and colleagues from the University of Oxford in the United Kingdom, reviewed 13 published trials on sexual abstinence-only programs for HIV prevention involving 15,940 youths in the United States. All biological and behavioral outcomes were self-reported.

The researchers found that the studies were heterogeneous and did not allow for a meta-analysis. Abstinence-only programs had no impact on the incidence of unprotected vaginal sex, condom use, number of partners or sexual initiation. The programs also had no effect on preventing sex or reducing the frequency of sex. Some trials showed protective and adverse effects of abstinence-only programs, but this was offset by other trials with non-significant findings.

"In contrast to abstinence-only programs, programs that promote the use of condoms greatly reduce the risk of acquiring HIV, especially when such programs are culturally tailored behavioral interventions targeting people at highest risk of HIV infection," Nancy B. Kiviat, M.D., from the University of Washington in Seattle, and colleagues write in an accompanying editorial.

AbstractFull TextEditorial

Program Cuts Door-to-Balloon Time in MI Patients

Regional percutaneous coronary intervention system extends benefits to hospitals up to 210 miles away

A regional coordinated care system designed to get myocardial infarction (MI) patients to percutaneous angioplasty centers quickly can decrease first door-to-balloon time and save more lives, researchers report in the Aug. 14 issue of Circulation: Journal of the American Heart Association.

Timothy D. Henry, M.D., of Abbott Northwestern Hospital in Minneapolis, and colleagues developed a program for transferring ST-elevation myocardial infarction patients to percutaneous coronary intervention (PCI) centers from 30 Minnesota community hospitals up to 210 miles away. The program involved standardizing care through the entire system using hospital specific protocols and rapid, coordinated transfer.

The 1,345 transfer patients were grouped into zones based on how far they traveled to the intervention center. The median door-to-balloon time for patients in zone 1, which fell within 60 miles of the center, was 95 minutes. The median door-to-balloon time was 120 minutes for those in zone 2, which fell within 60 to 210 miles outside the center. Overall, 79 percent of patients in zone 1 and 49 percent of patients in zone 2 achieved door-to-balloon times of under 120 minutes. The in-hospital mortality rate was 4.2 percent, and the average hospital stay was three days.

"A regional PCI system can extend the benefits of PCI to hospitals up to 210 miles away," the authors write.

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Early Statins Help Children with Familial Hypercholesterolemia

Treatment as early as age 8 delays damage due to inherited hypercholesterolemia

Early initiation of statin therapy can delay the onset of artery disease in children with familial hypercholesterolemia, Dutch researchers report in the Aug. 7 issue of Circulation: Journal of the American Heart Association.

Jessica Rodenburg, M.D., Ph.D., of the University of Amsterdam in the Netherlands, and colleagues analyzed the effects of 20 or 40 milligrams of pravastatin on blood lipid levels and carotid intima-media thickness in 214 children aged 8 to 18 with familial hypercholesterolemia.

The researchers found that children who started statin treatment early had a smaller carotid intima-media thickness than their peers who did not.

"These data indicate that early initiation of statin treatment delays the progression of carotid intima-media thickness in adolescents and young adults," the authors write. "The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might yield a large benefit in the prevention of atherosclerosis in adolescence."

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New Protocol Speeds Care for Rural Heart Attack Patients

Protocol speeds door-to balloon, door-to-needle times

A new protocol can optimize the timeliness of reperfusion therapy for myocardial infarction patients who are as far as 150 miles away from the nearest percutaneous coronary intervention center, according to a study in the Aug. 14 issue of Circulation: Journal of the American Heart Association.

Henry H. Ting, M.D., of the Mayo Clinic in Rochester, Minn., and colleagues implemented and evaluated a protocol that fast tracks rural patients with ST-elevation myocardial infarction who need reperfusion therapy. The protocol coordinates care between a percutaneous coronary intervention center and 28 regional hospitals located up to 150 miles away across three states. They treated 597 consecutive patients from May 2004 to December 2006.

Patients in group A presented at the percutaneous coronary intervention center and underwent primary angioplasty. Those in group B presented at a regional hospital more than three hours after symptom onset and were transferred to the angioplasty center. Those in group C came to a regional hospital less than three hours after symptom onset and received full-dose fibrinolytic therapy before being transferred to the main center.

Three-quarters of patients in group A and 12 percent of patients in group B achieved door-to-balloon times of less than 90 minutes. The median door-to-needle time was 25 minutes for group C, and 70 percent had times of less than 30 minutes.

"Novel and simple strategies and coordination of systems of care make these times achievable with a minimum of risk to patients," the authors write.

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Common Geriatric Conditions Linked to Disability

Dependency risk is highest in seniors with three or more geriatric conditions

In older adults, geriatric conditions that are not part of the traditional disease model of medicine are significantly associated with disability, according to the results of a study published in the Aug. 7 issue of the Annals of Internal Medicine.

Christine T. Cigolle, M.D., of the University of Michigan in Ann Arbor, and colleagues analyzed data from the 2000 Health and Retirement Study, which surveyed 11,093 adults aged 65 and older.

The researchers found that 49.9 percent of the subjects had at least one geriatric condition such as cognitive impairment, falls, incontinence, low body mass index and impaired vision or hearing. The prevalence of some conditions rivaled that of chronic diseases such as heart disease and diabetes. After adjusting for other factors including chronic diseases, they found a strong, linear association between the number of geriatric conditions and the risk of dependency on other people to perform activities of daily living, with adjusted risk ratios of 2.1 for one condition, 3.6 for two conditions, and 6.6 for three or more conditions.

"The findings suggest that geriatric conditions, although not a target of current models of health care, are important to the health and function of older adults and should be addressed in their care," the authors conclude.

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Physician Counsel Has No Effect on Motor Vehicle Safety

Routine in-office counseling doesn't improve seat-belt compliance, drinking-and-driving behavior

There is little evidence that primary care providers who counsel patients about the correct use of child safety seats and seat belts -- and the importance of not drinking and driving -- have a significant effect, according to two reports published in the Aug. 7 issue of the Annals of Internal Medicine.

In the first report, Ned Calonge, M.D., of the Colorado Department of Public Health and Environment in Denver, along with other members of the U.S. Preventive Services Task Force conducted a systematic review of English-language studies published through 2005. In the second study, Selvi B. Williams, M.D., of Kaiser Permanente Center for Health Research in Portland, Ore., and colleagues reviewed 17 randomized, controlled trials and controlled clinical trials.

Both studies found that community-based programs foster the proper use of child safety seats and seat belts, and that targeted counseling of persons with a history of alcohol abuse or drunk-driving arrests helps reduce future accidents. But neither study found that routine physician counseling on driving safety provided any additional benefits.

"Because the evidence is lacking to suggest a clear benefit from counseling about motor vehicle safety during regular doctors' visits, doctors and patients may choose to spend time on other preventive care issues during doctors' visits," according to an accompanying summary for patients. "However, because counseling is unlikely to be harmful, some doctors may choose to make it a regular part of their visits."

AbstractFull TextAbstractFull TextSummary for Patients

Non-Pharmaceutical Measures May Help with Flu Pandemic

School closures, isolation were effective during 1918-1919 outbreak

Non-pharmaceutical interventions such as school closures, prohibition of mass gatherings, isolation and quarantine helped to reduced the excess death rate during the 1918-1919 influenza pandemic and could help contain a future flu pandemic, according to study findings published in the Aug. 8 issue of the Journal of the American Medical Association.

Howard Markel, M.D., Ph.D., of the University of Michigan Medical School in Ann Arbor, and colleagues analyzed data from 43 cities during the period between September 1918 and February 1919 to see if non-pharmaceutical interventions had an impact on excess death rates.

During the six-month period studied, there were 115,340 deaths from pneumonia and influenza, yielding an excess death rate of 500 per 100,000 population. In all the cities, non-pharmaceutical measures were adopted to some extent. Thirty-four cities (79 percent) introduced school closures and bans on public gatherings for a median four weeks, which led to a significant reduction in the weekly excess death rate. Peak mortality was delayed the longest in cities that implemented non-pharmaceutical controls earliest. These cities also had lower peak mortality and total mortality rates.

"Although these urban communities had neither effective vaccines nor antivirals, cities that were able to organize and execute a suite of classic public health interventions before the pandemic swept fully through the city appeared to have an associated mitigated epidemic experience," the authors conclude.

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Underinsured Children Missing Out on Immunizations

Patchwork payment system denies some children access to publicly purchased vaccines

The near doubling of the recommended number of childhood vaccinations, the increased cost of fully vaccinating a child and changes in the medical insurance system have created new gaps in immunization coverage, researchers report in the Aug. 8 issue of the Journal of the American Medical Association.

Grace M. Lee, M.D., of Harvard Medical School and Harvard Pilgrim Health Care in Boston, and colleagues conducted the study by interviewing immunization program managers across 48 U.S. states.

In 70 percent of states, underinsured children were ineligible to receive publicly purchased meningococcal conjugate in the private sector, while those in 50 percent of the states were ineligible to receive pneumococcal conjugate vaccines. Citing lack of federal and state funding, 10 states changed their policies to restrict access to selected new vaccines for underinsured children.

"Despite the ability of vaccines to prevent illness and death, our current system of vaccine financing has resulted in a gap for underinsured children," the authors conclude. "Current trends in health insurance products, including enrollment in high-deductible health plans that may or may not provide immunizations or other preventive benefits before a high deductible has been met, are likely to increase the magnitude of this gap and must be carefully monitored."

AbstractFull Text (subscription or payment may be required)Editorial

Osteoporosis Treatment May Be Cost-Effective in Older Men

Strategy may benefit men over 64 with prior fracture, and men over 79 without prior fracture

Screening and treating older men for osteoporosis can be cost-effective, according to a report in the Aug. 8 issue of the Journal of the American Medical Association.

John T. Schousboe, M.D., of Park Nicollet Health Services in Minneapolis, and colleagues used a computer model to compare the cost-effectiveness of intervention or no intervention in populations of white men aged 65, 70, 75, 80 or 85 years with or without clinical fracture.

For men aged 65 years or older who had already had a fracture and for those aged 80 and older with no prior history of fracture, densitometry and follow-up costs were below $50,000. A number of factors had an impact on cost-effectiveness, including the cost of oral bisphosphonate and its efficacy in fracture reduction, the association between bone mineral density and fractures, fracture rates and disutility, and the extent to which patients adhered to the medication regimen.

"This strategy may be cost-effective for men aged 65 years or older with a prior clinical fracture and for men aged 80 years or older without a prior fracture, assuming a societal willingness to pay per quality-adjusted life-year gained of $50,000," the authors conclude, adding that societal acceptance of costs double that figure would make it cost-effective for white men aged 70 years or older regardless of fracture history.

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Researchers Fault Recent Meta-Analysis on Rosiglitazone

Re-analysis of data shows no increased or decreased risk of heart attack or death

Diabetic patients who take rosiglitazone (Avandia) have neither an increased nor decreased risk of myocardial infarction and cardiovascular death, according to an article published online Aug. 7 in the Annals of Internal Medicine.

George A. Diamond, M.D., of the University of California Los Angeles, and colleagues reviewed a recent, widely publicized meta-analysis of 42 clinical trials involving 27,847 patients that found that rosiglitazone was associated with a 43 percent increased risk of myocardial infarction and a 64 percent increased risk of death from cardiovascular disease.

Diamond and colleagues fault the original study's authors for not assessing the sensitivity of their conclusions to several methodological choices and for not including all studies showing evidence of rosiglitazone's cardiovascular effects. Using alternate meta-analytic approaches, they found lower odds ratios for myocardial infarction and cardiovascular death that were not statistically significant.

"In the end, we believe that only prospective clinical trials designed for the specific purpose of establishing the cardiovascular benefit or risk of rosiglitazone will resolve the controversy about its safety," the authors conclude. "In our opinion, available evidence does not justify what the authors of the original meta-analysis (as well as the media, the U.S. Congress, and worried patient groups) decried as an 'urgent need for comprehensive evaluations.'"

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Prophylactic Therapy Reduces Joint Damage in Hemophilia

More effective than episodic treatment

Among young boys with severe hemophilia, prophylactic treatment with factor VIII considerably reduces the risk of joint damage and hemorrhages compared with episodic treatment, researchers report in the Aug. 9 issue of the New England Journal of Medicine.

Marilyn J. Manco-Johnson, M.D., from the Mountain States Regional Hemophilia and Thrombosis Center in Aurora, Colo., and colleagues randomly assigned 65 boys younger than 30 months with severe hemophilia A to regular prophylactic infusions of recombinant factor VIII, or an enhanced episodic infusion schedule of factor VIII at the time of a joint hemorrhage. Bone or cartilage damage were detected by magnetic resonance imaging.

When the boys were 6 years old, significantly more boys in the prophylactic group had normal index-joint structure (93 percent versus 55 percent). Episodic treatment was associated with a higher risk of joint damage (relative risk 6.1) and significantly higher mean annual numbers of joint and total hemorrhages.

The study "provides renewed and detailed evidence that prophylaxis in severe hemophilia with recombinant factor VIII has clinical benefit despite its huge costs," Goris Roosendaal, M.D., Ph.D., and Floris Lafeber, Ph.D., from University Medical Center Utrecht in the Netherlands, write in an accompanying editorial. They note that the estimated cost of prophylaxis for one patient is $300,000 per year.

Bayer Healthcare donated the factor VIII used in the study.

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Drug Ineffective in Reducing Disability After Stroke

NXY-059 ineffective when given within six hours of symptom onset

A drug that traps free radicals and had shown promise in an earlier trial is ineffective in reducing disability after acute ischemic stroke when given within six hours of symptom onset, according to the results of a study published in the Aug. 9 issue of the New England Journal of Medicine.

Kennedy R. Lees, M.D., from the Gardiner Institute in Glasgow, United Kingdom, and colleagues randomized 3,306 patients with acute ischemic stroke to placebo or a 72-hour intravenous infusion of NXY-059 within six hours of stroke symptom onset.

The researchers found that after 90 days, both groups had similar disability scores on the modified Rankin scale. Both groups also had similar scores on the neurologic and activities-of-daily-living scales, and the mortality and adverse-event rate was similar, the authors note. In patients treated with alteplase, the frequency of symptomatic or asymptomatic hemorrhage was also similar in both groups.

"NXY-059 is ineffective for the treatment of acute ischemic stroke within six hours after the onset of symptoms," Lees and colleagues conclude.

The trial was sponsored by AstraZeneca.

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Rituximab Effective to Treat Severe Pemphigus

However, its use should be limited due to potential for life-threatening side effects

A single cycle of rituximab can be effective for treating patients with severe pemphigus who are not responding to corticosteroids, according to a report in the Aug. 9 issue of the New England Journal of Medicine. However, its use should be limited due to the drug's potentially life-threatening side effects.

Pascal Joly, M.D., Ph.D., from Rouen University Hospital in Rouen, France, and colleagues treated 21 patients with severe pemphigus that was corticosteroid-refractory or corticosteroid-dependent, or who had contraindications to corticosteroids, with four weekly infusions of rituximab (375 mg per square meter of body-surface area).

After three months, 18 patients (86 percent) had a complete remission, defined as epithelialization of all skin and mucosal lesions. Although nine patients relapsed after a mean of 18.9 months, 18 patients were disease-free after a median follow-up of 34 months. Eight patients were not taking corticosteroids, and the mean prednisone dose fell in patients taking corticosteroids. One patient developed pyelonephritis and another died from septicemia.

The study "supports previous reports that describe the beneficial effects of rituximab in the treatment of pemphigus without the need for infusions of intravenous immune globulins; however, its use must be restricted to a limited number of patients with pemphigus vulgaris or pemphigus foliaceus that is not responsive to conventional therapy…or to patients in whom these drugs may be harmful," states an accompanying editorial.

The study was partially supported by Roche.

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Prepared jointly by the editors of Medical Economics and HealthDay's Physicians' Briefing (www.physicianbriefing.com)