Latest Research

January 5, 2007

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

'Hospital Compare' Not a Good Indicator of Patient Outcome

Only small differences found in mortality between top and bottom ranked hospitals

The current set of performance measures provided by the U.S. Centers for Medicare & Medicaid Services' Hospital Compare Web site predict only small differences in patient outcome between hospitals ranked in top and bottom percentiles, according to a report in the Dec. 13 Journal of the American Medical Association.

Rachel Werner, M.D., Ph.D., and Eric Bradlow, Ph.D., both from the University of Pennsylvania in Philadelphia, determined whether the Hospital Compare quality measures accurately predict a hospital's risk-adjusted, condition-specific mortality rates for up to a year.

The researchers found that hospitals in the 75th percentile, ranked by Hospital Compare, had only minor improvements in patient mortality compared with those in the 25th percentile. For example, the mortality risk reduction across all acute myocardial infarction measures ranged from 0.005 for inpatients to 0.012 percent at one year. Similar small differences were seen for heart failure and pneumonia.

"These findings should not undermine current efforts to improve health care quality through performance measurement and reporting," the authors write. "However, attention should be focused on finding measures of health care quality that are more tightly linked to patient outcomes."

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Fifty Million in U.S. Financially Strained Due to Health Care

Study finds many spend more than 20 percent of income on health care

Almost 50 million young and middle-aged Americans, or about one in five people, live in families with very high financial burdens because of health care, spending 10 percent or more of their tax-adjusted income on health care services, researchers report in the Dec. 13 issue of the Journal of the American Medical Association.

Jessica Banthin, Ph.D., and Didem Bernard, Ph.D., from the U.S. Department of Health and Human Services in Rockville, Md., estimated the number and characteristics of individuals in the United States younger than 65 years faced with high financial burdens for health care. Data from the Medical Expenditure Panel Surveys were used to identify those spending more than 10 percent of their tax-adjusted family income on health care services.

In 2003, the researchers estimated that a total of 48.8 million persons fell into this group, up 11.7 million from 1996. About 18.7 million individuals spent more than 20 percent of their income on health care services.

In addition, the authors found that many individuals included in their estimates had non-group health insurance. "Persons with non-group plans are nearly three times as likely to bear high total burdens as individuals in any other insurance category, including the uninsured," they write.

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Therapy Bests Observation in Prostate Cancer Study

Treatment reduces mortality risk by around 30 percent in men with low-risk prostate cancer

A review of Medicare records suggests that treating 65- to 80-year-old men with low- or intermediate-risk localized prostate cancer, rather than just observing them, may reduce their mortality, according to a report in the Dec. 13 issue of the Journal of the American Medical Association.

Yu-Ning Wong, M.D., of Fox Chase Cancer Center in Philadelphia, and colleagues reviewed medical records of 44,630 men enrolled in the linked Surveillance, Epidemiology, and End Results (SEER) Medicare database to see if treating men with low- and intermediate-risk prostate cancer is beneficial.

At the end of a 12-year study period, 37 percent of the observational group had died compared to 23.8 percent of the treatment group who received either radical prostatectomy or radiotherapy. After adjustments, treatment was associated with a statistically significant hazard ratio of 0.69.

"Physicians should apply these provocative findings judiciously and continue their concerted efforts to help patients make informed treatment decisions based not only on survival predictions but also on health status, functional concerns and -- most importantly -- personal preference," cautioned Mark S. Litwin, M.D., M.P.H., and a colleague, in an accompanying editorial.

One of the authors in the original report serves an advisory role for Sanofi Aventis. Litwin has associations with TAP Pharmaceuticals, Amgen and Sanofi Aventis.

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Folic Acid Not Protective in Vascular Disease Patients

In patients with a history of cardiovascular disease, prevention should focus on proven strategies

Folic acid supplementation has no effect on the risk of cardiovascular disease in patients with pre-existing vascular disease, and prevention efforts should focus on proven strategies such as exercise and smoking cessation, according to a report published in the Dec. 13 issue of the Journal of the American Medical Association.

Lydia A. Bazzano, M.D., Ph.D., of Tulane University School of Public Health and Tropical Medicine in New Orleans, and colleagues performed a meta-analysis of 12 randomized controlled clinical trials examining the association between folic acid supplementation and cardiovascular disease. The trials involved 16,958 participants with pre-existing vascular disease and were identified from a MEDLINE search (January 1966-July 2006).

The researchers found that folic acid supplementation had no significant effect on the risk of cardiovascular disease, coronary heart disease, stroke or all-cause mortality.

"The findings of this analysis suggest that folic acid supplementation is ineffective in the secondary prevention of cardiovascular disease among persons with a history of vascular diseases," Bazzano and colleagues conclude. "Therefore, it is important to focus on strategies of proven benefit in the secondary prevention of cardiovascular disease, including smoking cessation, lipid reduction, treatment of hypertension and diabetes, maintenance of a healthy weight, and physical activity."

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Increased Risk of Cancer After Kidney Transplantation

Immune suppression may explain the increased risk

Kidney transplant patients are at higher risk of cancer at a variety of sites, suggesting that the link between the etiology of cancer and the immune system is stronger than previously thought, according to a study in the Dec. 20 issue of the Journal of the American Medical Association.

Claire M. Vajdic, Ph.D., of the University of New South Wales in Sydney, Australia, and colleagues analyzed data on 28,855 patients with end-stage kidney disease who had received renal replacement therapy and who were followed up for 273,407 person-years.

Cancers associated with end-stage kidney disease and non-melanoma skin cancer were excluded from the analysis, and after these exclusions, there were 1,236 cases of cancer, a 3.27 percent standardized incidence ratio (SIR). During dialysis, the SIR was only 1.35, with 870 reported cases. At 18 cancer sites, the SIR increased more than threefold after transplantation, usually due to a cancer with etiology thought or known to be viral.

"The magnitude and breadth of the increased risk after transplantation suggests that immune suppression causes a substantial and broad-ranging increase in cancer risk," the authors write. "Our findings point to an important role of the interaction between common viral infections and the immune system in the etiology of cancers at a broad range of sites."

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More Tumors Diagnosed After Medicare Screening Expands

More widespread use of colonoscopies, tumors being caught at earlier stage

Since Medicare expanded its coverage of routine colonoscopies, there has been an increase in the number of tumors diagnosed at an early stage, researchers report in the Dec. 20 issue of the Journal of the American Medical Association.

Cary P. Gross, M.D., of Yale University School of Medicine in New Haven, Conn., and colleagues analyzed data from three time periods: 1992 to 1997, when there was no Medicare screening coverage (period 1); January 1998 to June 2001, when there was limited coverage (period 2); and July 2001 to December 2002, when universal coverage was available (period 3).

The average rate of colonoscopy use in period 1 was 285/100,000 per quarter, rising to 889 in period 2, and 1,919 in period 3. Of the 44,924 eligible patients diagnosed with colorectal cancer, 22.5 percent were diagnosed at an early stage in period 1, versus 25.5 percent in period 2 and 26.3 percent in period 3. For patients with distal colon lesions, the Medicare policy change had little impact, but for those with proximal lesions, early diagnosis increased with the extent of Medicare coverage.

"Even a 4 percent increase in the percentage of patients whose cancer is diagnosed at an early stage can have a substantial impact at the population level," the authors write. "Increasing the use of screening tests further has the potential to diagnose many more beneficiaries at an early stage."

AbstractFull Text (subscription or payment may be required)Editorial

Vitamin D May Protect Against Multiple Sclerosis

Lowered risk most pronounced for those with high vitamin D levels before age 20

Higher serum 25-hydroxyvitamin D levels are associated with a lower multiple sclerosis risk, especially in those with elevated levels before age 20, researchers report in the Dec. 20 issue of the Journal of the American Medical Association.

Alberto Ascherio, M.D., of the Harvard School of Public Health in Boston, and colleagues used U.S. Defense Department data from more than 7 million U.S. military personnel collected between 1992 through 2004. They matched each of 257 multiple sclerosis cases with two controls and tested stored serum for 25-hydroxyvitamin D levels prior to diagnosis.

Among whites, the researchers found that higher vitamin D levels coincided with a significant drop in multiple sclerosis risk for 296 controls versus 148 patients (odds ratio 0.59 for a 50-nanomole-per-liter vitamin D increase).

Only the odds ratio for the top quintile was significantly different from 1.00. The researchers found an especially strong link between high vitamin D levels before age 20 and lower multiple sclerosis risk, but no significant link between vitamin D levels and multiple sclerosis risk in Hispanics and blacks, who had lower vitamin D levels than whites.

"The results of our study suggest that high circulating levels of vitamin D are associated with a lower risk of multiple sclerosis," the authors write.

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Cognitive Training Can Help the Elderly with Daily Functions

Effects can be long lasting; benefit seen in daily activities

Cognitive training can help improve the daily functioning of elderly patients, according to a report in the Dec. 20 issue of the Journal of the American Medical Association.

Sherry L. Willis, Ph.D., of Pennsylvania State University in State College, Pa., and colleagues studied 2,832 people with a mean age of 73.6 years in six U.S. cities randomized into four groups. Three of the groups received 10 sessions of training for verbal episodic memory; inductive reasoning; or visual search and identification (speed of processing). There were four booster training sessions for a random sample at 11 and 35 months. The fourth group received no interventions.

Compared with the control group, those in the inductive reasoning group reported improvements in the instrumental activities of daily living (IADL), although those in the visual search and identification and verbal episodic memory groups demonstrated little improvement.

There were mixed results for the booster training, which improved the functional measure for the speed of processing group but not in the other two groups, and booster training had no effect on self-reported IADL. The effects of the cognitive training were sustained at five years' follow-up, the report indicates.

"We…support future research to examine if these and other cognitive interventions can prevent or delay functional disability in an aging population," the authors write.

AbstractFull TextEditorial

Colonoscope Withdrawal Time Affects Adenoma Detection

Longer mean times detect significantly more neoplasia than shorter times

Endoscopists who have longer mean times for withdrawal of the colonoscope detect higher rates of adenomas, according to the results of a study published in the Dec. 14 issue of the New England Journal of Medicine.

Robert L. Barclay, M.D., of the University of Illinois College of Medicine at Rockford, Ill., and colleagues conducted a 15-month study of 12 gastroenterologists who performed 7,882 colonoscopies at a large community-based practice.

The researchers found that gastroenterologists with mean withdrawal times of the recommended six minutes or more had higher rates of detection of any neoplasia (28.3 percent versus 11.8 percent) and of advanced neoplasia (6.4 percent versus 2.6 percent).

"The results of this study are intuitive -- careful endoscopic examination of the colon should improve the rate of detection of adenomas, which is the important indicator of quality," states the author of an accompanying editorial. "Some may argue that measuring quality is onerous and cannot be accomplished efficiently in busy clinical practices. The current study by Barclay et al. shows that the members of a private group practice can 'take a look in the mirror' by asking critical questions about their daily practice and by measuring key outcomes to improve the quality of patient care."

AbstractFull Text (subscription or payment may be required)Editorial

Bevacizumab Boosts Survival, Bleed Risk in Lung Cancer

Risk of treatment-related death is higher with the drug

Adding bevacizumab to chemotherapy increases survival in patients with non-small-cell lung cancer but carries a higher risk of treatment-related deaths, according to a study in the Dec. 14 issue of the New England Journal of Medicine.

Alan Sandler, M.D., of Vanderbilt University in Nashville, Tenn., and colleagues randomly assigned 878 patients with recurrent or advanced non-small-cell lung cancer to chemotherapy with paclitaxel plus carboplatin alone or in combination with bevacizumab, a monoclonal antibody against vascular endothelial growth factor. Patients received chemotherapy every three weeks for six cycles and received bevacizumab every three weeks.

The researchers found a significant increase in median overall survival and median progression-free survival in patients receiving bevacizumab (12.3 months versus 10.3 months, hazard ratio 0.79; and 6.2 versus 4.5 months, hazard ratio 0.66; respectively). However, the risk of bleeding was significantly higher in patients receiving bevacizumab (4.4 versus 0.7 percent), with 15 treatment-related deaths compared with only two for chemotherapy alone.

"The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths," Sandler and colleagues conclude.

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Flu Shot Protects, Even in Years with Antigenic Drift

Inactivated or live attenuated vaccines, as well as school-based shots, protect patients and families

Both inactivated and live attenuated influenza vaccines protect adults from the flu, and school-based vaccination programs protect household family members, according to two studies conducted in 2004-2005, a year when flu vaccines were not well-matched to circulating strains. The findings are published in the Dec. 14 issue of the New England Journal of Medicine.

Suzanne E. Ohmit, Dr.P.H., of the University of Michigan School of Public Health in Ann Arbor, and colleagues studied 1,247 patients who randomly received either inactivated or live attenuated influenza vaccines in late 2004. Although most circulating viruses were dissimilar to those included in the vaccine during the ensuing flu season, the researchers found that both types of vaccine prevented influenza A (74 percent), but that live attenuated vaccine was less efficacious for influenza B (40 percent for live attenuated versus 80 percent for inactivated).

James C. King, Jr., M.D., of the University of Maryland in Baltimore, and colleagues identified 11 demographically similar clusters of elementary schools in four states and assigned one school in each to participate in a vaccination program, and one or two schools to act as controls. They found that intervention-school households had significantly fewer influenza-like symptoms and outcomes during a predicted week of peak influenza activity.

"Some have questioned whether the substantial effort to produce and deliver influenza vaccine is justified. The answer is, unambiguously, yes," state the authors of an accompanying editorial. "Indeed, the critical public health question is not whether influenza vaccines should be used, but how they can be used to advantage."

AbstractFull Text (subscription or payment may be required)AbstractFull Text (subscription or payment may be required)Editorial

Diagnoses of Ventilator- Associated Pneumonia Similar

Bronchoalveolar lavage, endotracheal aspiration have similar outcomes

Two techniques for diagnosing ventilator-associated pneumonia -- bronchoalveolar lavage and endotracheal aspiration -- are similar in terms of clinical outcomes and antibiotic use, researchers report in the Dec. 21 issue of the New England Journal of Medicine.

Daren Heyland, M.D., from Kingston General Hospital in Ontario, Canada, and colleagues randomly assigned 740 patients in the intensive care unit with suspected ventilator-associated pneumonia to a diagnosis by either bronchoalveolar lavage with quantitative culture or by endotracheal aspiration with non-quantitative culture. Patients known to be infected with pseudomonas species or methicillin-resistant Staphylococcus aureus were not included. All patients were given antibiotics until culture results were available, after which a targeted therapy was used to discontinue, reduce or resume antibiotics.

The researchers found that the two groups were similar in terms of mortality, rates of targeted therapy, days alive without antibiotics, maximum organ-dysfunction scores and length of stay in the hospital or ICU.

"Given the rapid emergence of antimicrobial resistance and the limited number of new antimicrobial agents, clinicians treating patients with suspected ventilator-associated pneumonia not only must prescribe appropriate initial antimicrobial regimens to optimize outcomes but also must minimize the development of resistance by rigorously using a de-escalation strategy," states an accompanying editorial. "When applied properly, bronchoalveolar lavage and endotracheal aspiration are tools that can facilitate de-escalation."

The study was supported by AstraZeneca and Bayer.

AbstractFull Text (subscription or payment may be required)Editorial

Antibiotic May Be Superior in Preventing Surgical Infection

Ertapenem better than cefotetan in preventing infection in study of colorectal surgery

The antibiotic ertapenem may be more effective than cefotetan in preventing surgical-site infections in patients undergoing colorectal surgery, according to study findings published in the Dec. 21 issue of the New England Journal of Medicine.

Kamal M.F. Itani, M.D., from Boston University Medical School, and colleagues randomly assigned 1,002 patients undergoing elective colorectal surgery to a single dose of 1 gram of ertapenem or 2 grams of cefotetan given within an hour before the first surgical incision. The final analysis included 334 cefotetan patients and 338 ertapenem patients who were evaluated four weeks after surgery.

The researchers found that prophylactic failure occurred in 42.8 percent of cefotetan patients and 28 percent of ertapenem patients. Surgical site infection was the most common reason for failure, occurring in 26.2 percent and 17.1 percent of cefotetan and ertapenem patients, respectively. There was a statistically insignificant increase in Clostridium difficile infection in the ertapenem patients (1.7 vs. 0.6 percent).

"Even though the authors demonstrated that ertapenem was superior to cefotetan in this trial, is it reasonable to conclude that ertapenem should be a preferred agent for prophylaxis before colorectal surgery?" according to an accompanying editorial. "Only one-third of Medicare patients undergoing colorectal surgery currently receive cefotetan as prophylaxis, and there are numerous other antibiotic regimens with a long track record of safety and efficacy."

The study was supported by Merck.

AbstractFull Text (subscription or payment may be required)Editorial

Biomarkers Only Small Help in Predicting Heart, Stroke Risk

Biomarkers not much more useful than conventional risk factors

A study of 10 biomarkers has found that they are not much more useful than conventional risk factors in determining the risk of cardiovascular disease and death, according to a report in the Dec. 21 issue of the New England Journal of Medicine.

Thomas J. Wang, M.D., from Massachusetts General Hospital in Boston, and colleagues examined the levels of 10 biomarkers from different biological pathways in 3,209 individuals in the Framingham Heart Study. The biomarkers were C-reactive protein, B-type natriuretic peptide, N-terminal pro-atrial natriuretic peptide, aldosterone, renin, fibrinogen, D-dimer, plasminogen-activator inhibitor type 1, homocysteine, and the urinary albumin-to-creatinine ratio.

After a median follow-up of 7.4 years, 207 individuals died and 169 had a first major cardiovascular event. Six biomarkers most strongly predicted risk of death, with adjusted hazard ratios per one standard deviation increment ranging from 1.17 to 1.4. Two biomarkers most strongly predicted major cardiovascular events, with adjusted hazard ratios of 1.25 and 1.2.

Using multimarker scores, the investigators found that those in the highest 20 percent had significantly higher risks of death (adjusted hazard ratio 4.08) and major cardiovascular events (adjusted hazard ratio 1.84) compared with the bottom 40 percent. However, this score only slightly increased the ability to classify risk compared with conventional risk factors.

The study "shows us how difficult it is to achieve effective risk stratification with respect to multifactorial disease processes," states an accompanying editorial.

AbstractFull Text (subscription or payment may be required)Editorial

PET Imaging Can Identify Alzheimer Disease

Imaging can differentiate between healthy people and various levels of cognitive impairment

Positron-emission tomography (PET) imaging using a particular ligand can differentiate between healthy patients, those with mild cognitive impairment and those with Alzheimer disease, according to the results of a study published in the Dec. 21 issue of the New England Journal of Medicine.

Gary W. Small, M.D., and colleagues from the University of California Los Angeles performed PET imaging in 83 volunteers with self-reported memory problems using a small molecule called 2-(1-(6-(2-F-18 fluoroethyl)(methyl)amino-2-naphthyl)ethylidene)malononitrile, or FDDNP, which binds to plaques and tangles in vitro, and 2-deoxy-2-F-18 fluoro-D-glucose (FDG).

Seventy-two volunteers also underwent magnetic resonance imaging. Cognitive testing showed that 25 volunteers had Alzheimer disease, 28 had mild cognitive impairment and 30 had no cognitive impairment.

The researchers found significantly higher global FDDNP binding (average of four brain regions) in volunteers with Alzheimer disease, followed by less binding in those with mild cognitive impairment, and even less in healthy controls. FDDNP binding correlated better with diagnosis than FDG binding or magnetic resonance imaging, according to the study.

"FDDNP-PET scanning can differentiate persons with mild cognitive impairment from those with Alzheimer disease and those with no cognitive impairment," Small and colleagues conclude. "This technique is potentially useful as a non-invasive method to determine regional cerebral patterns of amyloid plaques and tau neurofibrillary tangles."

UCLA owns a U.S. patent, Methods for Labeling Beta-Amyloid Plaques and Neurofibrillary Tangles, that uses the approach described in this article.

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Agalsidase-Beta Effective for Fabry Disease

Drug lowers risk of clinical events in patients with advanced Fabry disease

Agalsidase-beta lowers the risk of clinical events in patients with advanced Fabry disease, a rare, X-linked lysosomal storage disorder that affects heart and kidney function, according to a study in the Jan. 16 issue of the Annals of Internal Medicine.

Robert J. Desnick, M.D., Ph.D., from Mount Sinai School of Medicine in New York City, and colleagues randomized 82 patients with Fabry disease and mild to moderate kidney disease to intravenous placebo (31 patients) or agalsidase-beta (1 mg/kg, 51 patients) every two weeks for a median of 18.5 months. Nearly 90 percent of the patients were men.

Forty-two percent of placebo patients compared with 27 percent of agalsidase-beta patients had a clinical event (renal, cardiac or cerebrovascular event, or death). In the 74 protocol-adherent patients, after adjusting for baseline proteinuria, agalsidase-beta significantly delayed the time to first clinical event (hazard ratio 0.39). This risk reduction was most pronounced in patients with a preserved baseline glomerular filtration rate of more than 55 mL/min per 1.73 square meters (hazard ratio 0.19). Most adverse events were infusion-associated reactions.

The study "provides a crucial path toward lowering the morbidity of Fabry disease," states the author of an accompanying editorial.

The study was funded by the National Center for Research Resources and the Genzyme Corporation.

AbstractFull Text (subscription or payment may be required)Editorial

Black Cohosh Ineffective in Treating Menopause

Herbal supplement no more effective than placebo in well-designed trial

The herbal supplement black cohosh alone or combined with other supplements is ineffective at reducing the frequency or severity of menopausal symptoms, according to the results of a randomized, controlled trial published in the Dec. 19 issue of the Annals of Internal Medicine.

Katherine M. Newton, Ph.D., from the University of Washington in Seattle, and colleagues studied 351 women who were either postmenopausal or in menopausal transition and who had at least two vasomotor symptoms per day. The women were randomly assigned to black cohosh, a multibotanical with black cohosh and nine other ingredients, a multibotanical plus dietary soy counseling, estrogen plus or minus medroxyprogesterone acetate, or placebo for one year.

None of the three herbal interventions had any effect on the frequency or intensity of vasomotor symptoms compared with placebo, apart from significantly worse symptom intensity after 12 months with the multibotanical plus soy intervention. In contrast, hormone therapy significantly reduced the frequency and severity of symptoms compared with placebo.

"The study is a well-designed, adequately powered randomized controlled trial that makes an important contribution, albeit one that will disappoint women who have been hoping for an effective, safe alternative to estrogen," states the author of an accompanying editorial. However, the editorialist notes that women in the placebo group had a 30 percent reduction in the severity and frequency of symptoms, suggesting some women "may not need treatment at all."

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Not-for-Profit Hospitals Deliver Better Patient Care

Facilities with more nurses and more investment in technology also have better service quality

Not-for-profit hospitals and hospitals with high nurse ratios and greater investment in technology deliver better patient care, according to a report published in the Dec. 11/25 issue of the Archives of Internal Medicine.

Bruce Landon, M.D., M.B.A, of Harvard Medical School in Boston, and colleagues analyzed data submitted for the first half of 2004 to the American Hospital Association from over 4,000 hospitals on treatment of patients with congestive heart failure, acute myocardial infarction and pneumonia, creating composite scales for each disease.

For patients with each condition, profit-making hospitals underperformed their not-for-profit counterparts. Teaching hospitals scored better performance in terms of treatment and diagnosis but had worse performance in counseling and prevention compared to non-teaching facilities. Hospitals with higher registered nurse staffing and more technology performed better as well. Higher performance was also noted in hospitals with federal/military designation, a finding that indicates there are valuable lessons to be learned from the last decade of quality improvement undertaken by the Veterans Health Administration.

"Our results also suggest that characteristics of hospitals, including ownership, teaching status, location and accreditation, are significant predictors of performance," the authors conclude. "Because payments and sources of payments affect some of these factors (e.g., investments in technology and staffing ratios), policy makers should evaluate the effect of alternative payment approaches on quality."

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Caloric Restriction-Induced Weight Loss Harms Bones

Weight loss through exercise has no deleterious effect on bone

Men and women who lose weight by reducing their caloric intake may lose bone mineral density, but people who shed pounds by exercising do not, according to the results of a study published in the Dec. 11/25 issue of the Archives of Internal Medicine.

Dennis T. Villareal, M.D., of Washington University School of Medicine in St. Louis, and colleagues studied the effects of weight loss on bone density in 48 adults. Participants who followed a calorie-restricted diet lost an average of 10.7 percent of their body weight after one year. Participants in the exercise group lost an average of 8.4 percent of their body weight, and participants in the control group who received information on healthy lifestyles upon request maintained their weight at one year.

Individuals in the caloric-restriction group also lost an average of 2.2 percent of their bone density in the lower spine, 2.2 percent at the hip and 2.1 percent at the top end of the femur. By contrast, there were no significant changes in bone mineral density in the exercise or control groups. Bone turnover increased in both weight-loss groups.

"These data suggest that exercise should be an important component of a weight-loss program to offset adverse effects of caloric restriction on bone," the authors conclude.

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Massage Therapy May Relieve Pain of Knee Osteoarthritis

Swedish massage induces more flexibility and less pain

Swedish massage can effectively reduce pain and increase flexibility in patients with osteoarthritis of the knee, according to a report published in the Dec. 11/25 issue of the Archives of Internal Medicine.

David L. Katz, M.D., M.P.H., of the Yale Prevention Research Center of Yale University School of Medicine in Derby, Conn., and colleagues conducted a study of 68 adults with osteoarthritis who were randomized to receive either twice-weekly sessions of Swedish massage for four weeks followed by once-weekly sessions for four weeks, or to a control group with delayed intervention.

Scores for pain, stiffness and physical function all improved significantly in the massage group, according to scores on the Western Ontario and McMaster Universities Osteoarthritis Index. The visual analog scale of pain assessment, range of motion in degrees, and time to walk 50 feet in seconds were also improved. The results remained consistent even when demographic factors were taken into account.

"Massage therapy seems to be efficacious in the treatment of osteoarthritis of the knee," the authors conclude. "Further study of cost effectiveness and duration of treatment effect is clearly warranted."

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All-Cause Mortality Lower in Moderate Alcohol Consumers

Benefits disappear beyond a couple of glasses of wine or beer a day

Moderate alcohol consumption, defined as a maximum of one to two glasses a day for women and two to four glasses a day for men, is associated with lower all-cause mortality compared to those who don't drink, according to a report published in the Dec. 11/25 issue of the Archives of Internal Medicine.

Licia Iacoviello, M.D., Ph.D., of the Catholic University in Campobasso, Italy, and colleagues conducted a meta-analysis of 34 studies including a total of 1,015,835 men and women and 94,533 deaths.

There was an inverse association between daily consumption of up to four alcoholic drinks for men and one or two for women and total mortality. The maximum protection was 18 percent in women and 17 percent in men. However, daily consumption of alcohol in larger amounts was associated with increased mortality and women were susceptible to the negative effects of alcohol at lower doses than men.

"It might be a fact linked to the metabolism. We know that women metabolize alcohol in a different way and the blood concentration reaches higher levels. Therefore, consuming more than two doses might lead to several harmful effects, such as liver diseases or increased risk of certain forms of tumor," said Iacoviello in a statement.

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Height Loss in Older Men Linked to Mortality Risk

Men who shrink more than 3 centimeters have higher rates of coronary artery disease

Men who lose 3 centimeters or more in height as they age are more likely to develop coronary artery disease and have higher all-cause mortality than those who do not lose height, researchers report in the Dec. 11 issue of the Archives of Internal Medicine.

S. Goya Wannamethee, Ph.D., of the Royal Free and University College Medical School in London, U.K., and colleagues studied 4,213 men whose height was measured when they were aged 40 to 59 and then measured again 20 years later. During the mean six-year follow-up period, 760 men in the sample died.

Among men who lost 3 centimeters in height or more, there was a 1.64 times higher risk of mortality compared with men who lost less than 1 centimeter in height. The increased number of deaths was attributed to cardiovascular and respiratory disease. Adjustments for age, other cardiovascular risk factors, lung function, pre-existing cardiovascular disease, albumin concentration, self-reported poor health and weight loss had only a modest impact, with an adjusted relative risk of 1.45.

"Despite a strong association between height loss and weight loss, we observed no association between height loss and cancer mortality," the authors note. "Height loss may be a marker for sarcopenia and frailty in older men," they conclude.

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Postmenopausal Breast Cancer Risk Lower with Exercise

Positive effects of exercise more potent in ER+/PR- tumors

Postmenopausal women who report high levels of physical activity are at reduced risk of developing breast cancer, especially estrogen receptor-positive/progesterone receptor-negative tumors (ER+/PR-), than women who are less active, according to data from the Iowa Women's Health Study published in the Dec. 11/25 issue of the Archives of Internal Medicine.

Aditya Bardia, M.D., M.P.H., of the Mayo Clinic College of Medicine in Rochester, Minn., and colleagues tracked women's self-reported levels of physical activity and breast cancer incidence, including tumor status, in a cohort of 41,836 women over 18 years.

Women who reported high levels of physical activity had a 14 percent lower risk of developing breast cancer, compared with their less-active counterparts, and a 9 percent lower risk of breast cancer after researchers controlled for body mass index (BMI). This suggests that not all of the association was due to the effect of exercise on body weight. The association was strongest among women with ER+/PR- tumors. Specifically, women with high physical activity levels had a 34 percent lower risk of developing this type of cancer after adjusting for BMI.

"If found to be causally related to breast cancer, physical activity would have a substantial public health effect on the prevention of this disease, along with its other positive health benefits," the authors conclude.

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Children With High IQ More Likely to Become Vegetarians

Higher IQ at age 10 associated with preference for meat-free diet at age 30

Children with high IQ scores are more likely to become vegetarians as adults, compared to their counterparts with normal or lower IQ, according to a study published online Dec. 15 in BMJ.

Catharine R. Gale, Ph.D., of the University of Southampton in Southampton, U.K., and colleagues conducted a study of 8,170 men and women who participated in the 1970 British cohort study and who were 30 when interviewed regarding their dietary habits.

A vegetarian diet was reported by 366 (4.5 percent) of the subjects, of whom 123 (33.6 percent) said they also ate fish and chicken. Female sex, higher social class both at birth and at the time of the study, and higher educational level at the time of the study, whether or not these factors were reflected in current income, were all associated with vegetarianism.

Men and women who reported being vegetarian had mean childhood IQ scores of 106.1 and 104.0, respectively, compared to 100.6 and 99.0 for non-vegetarian men and women, respectively.

The report did not draw any firm conclusions on the cause of the link, suggesting that vegetarianism may mediate the association between coronary heart disease in adulthood and childhood IQ. Alternatively, "the association between IQ and vegetarianism may be merely an example of many other lifestyle preferences that may be expected to vary with intelligence," they write.

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Animals Models for Human Drug Trials of Limited Use

Biological differences and bias may explain discordance with human studies

The results of animal studies for new drugs are often out of step with those from human trials, limiting their usefulness, according to a report published online Dec. 15 in BMJ.

Ian Roberts, M.D., Ph.D., of the London School of Hygiene and Tropical Medicine in the U.K., and colleagues conducted a systematic review of trials with unambiguous results for various interventions including treatment for stroke, head injury, respiratory distress and osteoporosis.

There were several striking examples of discordance between animal and human trials, such as those studying the effect of corticosteroids in the treatment of head injury, which showed no benefit in clinical trials despite showing benefit in animal models. Similarly, animals trials of tirilazad to treat stroke had positive results, but human trials contradicted the findings, suggesting no benefit and possible harm.

"That there is a gap between clinical research and clinical practice is well established. Our work highlights another gap -- specifically the lack of communication between those involved in animal research and clinical trialists," the authors conclude. "Systematic reviews could help identify and improve deficiencies in the conduct and reporting of animal research."

Some support was received by Pharmacia, Upjohn and Boehringer Ingelheim.

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Sleeping in Car Seat Can Be Dangerous for Infants

Report describes nine infants in New Zealand who experienced potentially life-threatening events

Young infants should not be allowed to fall asleep in car safety seats for extended periods since this can cause potentially life-threatening breathing problems, according to a report in the Dec. 9 issue of BMJ.

Alistair J. Gunn, M.D., Ph.D., from the University of Auckland in New Zealand, and colleagues describe the cases of nine infants (age range 3 days to 6 months) who had been restrained in an age-appropriate car safety seat and subsequently had apparently life-threatening events and turning blue. Only one of the infants had been born prematurely and in all but one case the infant had been left in the car seat indoors and allowed to fall asleep in a relatively upright position.

The researchers reconstructed the scene, using each infant's own car seat. They found that sleeping in the car seat caused the jaw to press on the chest, leading to pressure on the upper airway and subsequent breathing problems. The infants were followed-up with apnea monitors and parents were given advice on how to appropriately position the infant and told not to leave the infant in the car seat for excessive periods. There were no similar events over the next year, the report indicates.

"Half of the mothers in our study were smokers, and nicotine exposure could have reduced hypoxic arousal," the authors write. "Repeated episodes of mild hypoxia may lead to an 'habituation' effect, with failure to arouse to subsequent episodes."

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Breast Cancer Survivors Can Attempt Pregnancy Sooner

Waiting six months after treatment, rather than two years, seems to be safe

Women who have survived localized breast cancer may be able to safely attempt pregnancy within a relatively short period of time, such as six months after treatment, rather than waiting at least two years as is currently recommended, according to a study published online Dec. 8 in BMJ.

Angela Ives, M.Sc., from the University of Western Australia in Crawley, and colleagues identified 123 women under 45 years old who survived breast cancer and had at least one subsequent pregnancy. Fifty-four percent conceived less than two years after being diagnosed with breast cancer.

The researchers found that survival was better in women who conceived (hazard ratio, 0.59) than those who did not. When they looked at time-to-pregnancy after treatment ended, they found that women who waited at least 24 months to conceive had a significant protective effect (hazard ratio, 0.48) compared to women who did not become pregnant, and there was a non-significant protective effect for those who waited at least six months.

"Our study does not support the current medical advice given to premenopausal women with a diagnosis of breast cancer to wait two years before attempting to conceive," Ives and colleagues conclude. "This recommendation may be valid for women who are receiving treatment or have systemic disease at diagnosis, but for women with localized disease early conception, six months after completing their treatment, is unlikely to reduce survival."

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Two Types of Heart Disease Imaging Complementary

Scan identifies atherosclerosis while perfusion imaging detects ischemia

Multi-slice computed tomography (MSCT) and myocardial perfusion imaging (MPI) play complementary roles in providing information about coronary artery disease, according to study findings published in the Dec. 19 issue of the Journal of the American College of Cardiology.

Jeroen J. Bax, M.D., Ph.D., of Leiden University Medical Center in the Netherlands, and colleagues conducted a study of 114 patients, most of whom had intermediate likelihood of coronary artery disease, and who all underwent both MSCT and MPI. The results of the MSCTs were classified as showing no coronary artery disease, non-obstructive coronary artery disease with less than 50 percent luminal narrowing, or obstructive coronary artery disease. The MPI results were classified as showing either normal or abnormal results. Invasive coronary angiography was performed in a subset of 58 patients.

A total of 41 patients (36 percent) had no coronary artery disease based on the MSCT data, of whom 90 percent had normal MPI. Thirty-three patients (29 percent) had non-obstructive coronary artery disease and 40 patients (35 percent) had at least one significant lesion. Among the patients with abnormal MSCT results, only 45 percent had abnormal MPI; and 50 percent of those with an obstructive coronary artery disease result from the MSCT had a normal MPI. The correlation with MSCT was 90 percent in those undergoing angiography.

"MPI and MSCT provide different and complementary information on coronary artery disease, namely, detection of atherosclerosis versus detection of ischemia," the authors conclude. "As compared to invasive angiography, MSCT has a high accuracy for detecting coronary artery disease in patients with an intermediate likelihood of coronary artery disease."

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Nicotine Can Spur New Blood Vessel Growth

The chemical mobilizes endothelial progenitor cells in animals

Nicotine can stimulate the growth of endothelial progenitor cells in bone marrow, and can induce capillary growth in ischemic tissue, according to the results of a mouse study published in the Dec. 19 issue of the Journal of the American College of Cardiology.

John P. Cooke, M.D., Ph.D., of Stanford University School of Medicine in Stanford, Calif., and colleagues administered nicotine to mice that had induced unilateral hind leg ischemia. The investigators found it increased the density of the capillaries in that area. Systemic delivery of nicotine produced a 76 percent increase in capillary density versus 45 percent for local delivery compared with vehicle control.

While there were rare instances of ischemia-induced incorporation of endothelial progenitor cells in capillaries in the control group, this increased fivefold when the mice were administered systemic nicotine. Nicotine also increased the number of endothelial progenitor cells in the bone marrow and spleen.

"Administration of nicotine increased markers of endothelial progenitor cell mobilization. This study indicates that the known angiogenic effect of nicotine may be mediated in part by mobilization of precursor cells," the authors conclude.

In an accompanying editorial, Angelo Avogaro, M.D., Ph.D. and Gian Paolo Fadini, M.D., of the University of Padova in Italy, comment that there are still unanswered questions, such as why nicotine did not stimulate mobilization of endothelial progenitor cells except in the presence of acute ischemia.

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Heart Disease and Stroke Should Be Reportable Diseases

American Heart Association suggests annual, national reporting needed on progress in fight against cardiovascular disease

If stroke and heart disease were to become reportable diseases, efforts to reduce incidence could be more accurately measured, according to a statement by the American Heart Association published Dec. 18 in Circulation: Journal of the American Heart Association.

"We believe that we know so much about how to prevent heart disease that, when it occurs, it represents a failure of the public health and medical systems that should be reported to the appropriate agency," David C. Goff, Jr., M.D., Ph.D. of Wake Forest University School of Medicine in Winston Salem, N.C., said in a statement. "We already have some information based on hospitalizations, but that can be hard to interpret. For example, if the data doesn't distinguish between first heart attacks and subsequent attacks, it can be misleading."

Goff and colleagues classified a number of overall and goal-specific recommendations according to their priority and capacity to cut costs.

A National Heart Disease and Stroke Surveillance unit is needed to publish information on prevention and management of the two conditions, a move that the authors afforded high priority. Compulsory reporting of a range of cardiovascular disease conditions was also given top priority although this was not as urgent a task as setting up national surveillance. Data collection also requires standardization, the statement said.

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Quicker Time to CPR Improves Survival

New resuscitation protocol recommends longer CPR initiated immediately after defibrillation

A new protocol in which cardiopulmonary resuscitation (CPR) is given immediately after defibrillation and for a longer period of time significantly improves survival of cardiac arrest patients compared with multiple shocks, pulse checks and shorter CPR, according to a report published online Dec. 11 in Circulation: Journal of the American Heart Association.

The protocol is in line with the 2005 American Heart Association guidelines, which placed more emphasis on CPR. A year before the guidelines were introduced, Thomas D. Rea, M.D., M.P.H., of the University of Washington in Seattle, and colleagues implemented a new protocol calling for a single shock from a defibrillator immediately followed by two minutes of CPR. The old protocol called for multiple shocks and pulse checks before starting CPR and continuing for one minute.

The new protocol was tested for one year on 134 individuals who had a bystander-witnessed out-of-hospital ventricular fibrillation arrest because of heart disease. The results were compared with results from 374 individuals from the previous three years.

The new protocol significantly improved survival to hospital discharge (46 percent versus 33 percent), which correlated with the fact that chest compressions were started significantly sooner after defibrillation (7 seconds versus 28 seconds).

"These results suggest the new resuscitation guidelines will alter the interface between defibrillation and cardiopulmonary resuscitation and may in turn improve outcomes," Rea and colleagues conclude.

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Drawing Impairment Associated with COPD Mortality

Test results might predict cognitive decline, mortality in COPD patients

Chronic obstructive pulmonary disease (COPD) patients unable to copy certain drawings as part of neuropsychological testing have a higher rate of mortality compared to those who can complete the test, according to a report in the December issue of Chest.

Andrea Corsonello, M.D., of the Italian National Research Center on Aging in Cosenza, Italy, and colleagues tracked 134 patients with stable COPD for 32 months to evaluate the impact of cognitive impairment on survival.

The researchers found that 58.6 percent of those who died during the observation period had abnormal scores on complex drawing tests compared with 35.2 percent of survivors. Only drawing scores and six-minute walking distance were associated with mortality.

"In conclusion, the copying of a drawing with landmarks test can be used as a prognostic marker in COPD patients," the authors write. "Future research should verify whether this finding reflects a distinctive impairment of executive dysfunction in patients with severe COPD or, alternatively and mimicking the early stages of Alzheimer disease, a constructional dyspraxia due to right insular involvement."

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Depression Common in Patients with Chronic Cough

Over half of patients evaluated for chronic cough have depressive symptoms

Physicians and caregivers should be aware of the significant risk of clinical depression in patients with chronic cough, researchers report in the December issue of Chest.

Peter Dicpinigaitis, M.D., from the Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, N.Y., and colleagues conducted a prospective, non-randomized evaluation of patients seeking treatment for chronic cough to determine the prevalence of depressive symptomatology in this group.

The investigators found that 53 of 100 patients scored positive on the Center for Epidemiologic Studies Depression Scale exam, with a mean score of 18.3. Both cough and depressive symptoms improved during a three-month follow-up and were significantly correlated with each other.

"Clinicians should exercise judgment in deciding whether appropriate mental health referral is necessary, regardless of the outcome of treatment for chronic cough," the authors conclude.

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Being Male and Overweight Increases Habitual Snoring Risk

Cigarette smoking and asthma also increase chances of problem snoring

Men who are obese, who gain weight, start smoking or develop asthma are at risk for becoming habitual snorers, researchers report in the December issue of Chest.

Matthew Knuiman, Ph.D., of the University of Western Australia in Perth, and colleagues compared body weight and respiratory risk factors in 967 adults between 25 and 74 years of age who did not report snoring in a 1981 survey and who were reassessed in a 1994-1995 survey.

The researchers found that 13 percent of the initial non-snorers snored habitually when followed up in 1994-1995. Key risk factors were being male (odds ratio, 3.5) and body mass index at baseline (OR, 1.4 per 3.4 kilograms per square meter).

Other habitual snoring risk factors included starting smoking, development of asthma, and body mass index changes during the 14-year follow-up, the report indicates.

"This study has confirmed male gender, obesity and weight gain as key determinants of habitual snoring, and has indicated that development of asthma and taking up smoking also play a role," the authors write. "Maintaining a healthy weight and not smoking are recommended lifestyle preventive strategies to reduce the risk of sleep-disordered breathing and its sequelae."

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Sleep Apnea Therapy Improves Memory Performance

Regular CPAP users show nearly eightfold increase in performance compared with irregular users

Patients with obstructive sleep apnea who adhere to their nightly positive airway pressure treatments may improve their verbal memory performance during the day, researchers report in the December issue of Chest.

Molly Zimmerman, Ph.D., of Albert Einstein College of Medicine, Bronx, N.Y., performed neuropsychological tests on 58 memory-impaired patients with obstructive sleep apnea before and after a three-month period of continuous positive airway pressure (CPAP) treatment. Patients were categorized based on their adherence to treatment guidelines, which was covertly monitored with a microchip processor.

The investigators found that optimal users increased their memory performance 7.9-fold over poor users and were more likely to exhibit clinically normal memory performance. Optimal therapy use was defined as greater than six hours per night.

"CPAP has proven to be an effective treatment for patients with obstructive sleep apnea yet adherence to treatment remains poor," said Mark J. Rosen, M.D., F.C.C.P., president of the American College of Chest Physicians, in a statement. "Physicians should educate their patients with obstructive sleep apnea about the importance of using CPAP consistently and discuss ways to overcome obstacles to adherence."

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