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Latest Research


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

Genetic Polymorphisms Affect Antidepressant Response

Findings could lead to pharmacogenetic selection of antidepressants

In patients with late-life depression, antidepressant response is significantly affected by the presence of monoamine transporter gene polymorphisms, according to the results of a preliminary study published in the Oct. 4 issue of the Journal of the American Medical Association. If the findings are confirmed, they could lead to a more refined selection of antidepressant treatment, the authors write.

Hyeran Kim, M.D., of Sungkyunkwan University School of Medicine in Seoul, Korea, and colleagues studied 241 older Korean patients who were treated for six weeks with either a selective serotonin reuptake inhibitor (SSRI; fluoxetine or sertraline) or a norepinephrine reuptake inhibitor (nortriptyline).

The researchers found that response to nortriptyline was associated with the NET G1287A polymorphism (odds ratio, 7.54) and that patients who carried this polymorphism had a significantly higher response to nortriptyline treatment than to SSRI treatment (83.3 percent versus 58.7 percent). They also found that the 5-HTTLPR s/l variation was associated with an SSRI response (odds ratio, 20.11) and that the 5-HTTLPR polymorphism was associated with an SSRI response (odds ratio, 3.34).

"The results of this study need to be confirmed in other populations, using selective norepinephrine reuptake inhibitors other than nortriptyline. Additional studies in younger populations with depression are also needed," the authors write. "Confirmation of these preliminary findings would permit refined pharmacogenetic selection of antidepressant treatment," they conclude.

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MRI Scans Recommended for Children with Cerebral Palsy

Scans show pathologic basis of condition and may help predict children's function and future needs

All children with cerebral palsy should have a magnetic resonance imaging (MRI) scan because there is a strong correlation with clinical findings and the scan can help predict children's future needs, as well as possibly help prevent future cases, researchers report in the Oct. 4 issue of the Journal of the American Medical Association. More than 40 percent of such children have white-matter damage of immaturity and only about 12 percent have no abnormalities on MRI.

Martin Bax, D.M., of Imperial College London in the U.K., and colleagues clinically assessed 431 children with cerebral palsy and examined MRI scans from 351 that were conducted at 18 months or later. Scans were scored by two reviewers blinded to the clinical findings.

The researchers found a high rate of infections (39.5 percent) reported by the children's mothers during pregnancy and that 12 percent of the children were from multiple pregnancies. The most common clinical diagnosis was diplegia (34.4 percent) and the most common MRI finding was white-matter damage of immaturity (42.5 percent) followed by a variety of lesions, malformations and infarcts.

"The report by Bax and colleagues in this issue of JAMA is a major advance," states the author of an accompanying editorial. "By obtaining MRI scans at 18 months, the completion of the early developmental stages of central nervous system structural integrity can be linked to the expanded neuromotor classification. Because of the large sample, this study provides some preliminary observations of timing, clinical risks, and functional impact on sitting balance, hand function, and communicative skills."

AbstractFull Text (subscription or payment may be required)Editorial

Sudden Cardiac Deaths Decline in Young Italian Athletes

Researchers credit introduction of screening program to detect structural heart disease

After the 1982 introduction of a systematic, nationwide cardiovascular screening program for young athletes in Italy, the annual incidence of sudden cardiovascular deaths has significantly declined, according to a study published in the Oct. 4 issue of the Journal of the American Medical Association.

Domenico Corrado, M.D., of the University of Padua Medical School in Italy, and colleagues analyzed cardiovascular death in young athletes, aged 12 to 35, between 1979 and 2004.

The researchers identified 55 sudden cardiovascular deaths in screened athletes (1.9 deaths/100,000 person-years) and 265 sudden deaths in unscreened non-athletes (0.79 deaths/100,000 person-years). Between 1979-1980 and 2003-2004, they calculated that the annual incidence of sudden cardiovascular death in athletes decreased by 89 percent.

"The study by Corrado et al. provides the best evidence to date supporting the pre-participation screening of athletes and provocative evidence for including ECGs in this process," state the authors of an accompanying editorial. "However, cardiologists and other physicians involved in the evaluation of athletes can take a valuable lesson from Corrado et al., and collaborate to develop a rigorous, comprehensive regional or national registry to study the pre-participation screening process prospectively and directly, and to determine how to implement such programs most effectively and how to manage asymptomatic athletes with cardiac abnormalities detected by the screening process."

AbstractFull TextEditorial

Psoriasis Associated with Myocardial Infarction Risk

Younger patients with severe disease at higher risk

Psoriasis may increase the risk of having a myocardial infarction, particularly in younger patients with severe disease, according to study results published in the Oct. 11 issue of the Journal of the American Medical Association.

Joel M. Gelfand, M.D., and colleagues from the University of Pennsylvania in Philadelphia, examined the association between psoriasis and myocardial infarction in 127,139 patients with mild psoriasis, 3,837 patients with severe psoriasis and 556,995 matched controls. Subjects were 20 to 90 years of age and lived in the United Kingdom.

After a mean follow-up of 5.4 years, the researchers found that the incidence of myocardial infarction per 1,000 person-years was 4.04 for patients with mild psoriasis, 5.13 for patients with severe psoriasis and 3.58 for controls. The relative risk of having a myocardial infarction in patients with psoriasis varied with age and was highest for younger patients with severe psoriasis, with a relative risk of 3.10 for a 30-year-old and a relative risk of 1.36 for a 60-year-old patient.

"Psoriasis may confer an independent risk of myocardial infarction," Gelfand and colleagues conclude. "The magnitude of association between severe psoriasis and myocardial infarction in those patients younger than 50 years is similar to the magnitude of association for other major cardiac risk factors."

The study was supported in part by Biogen Idec.

AbstractFull Text

Vaccination Exemptions Linked to Pertussis Infections

States that allow personal exemptions have a 50 percent higher rate of pertussis infection

States that allow exemptions from school immunizations too easily, or that allow exemptions for personal beliefs, have about a 50 percent higher rate of pertussis infection, according to a report in the Oct. 11 issue of the Journal of the American Medical Association.

Daniel A. Salmon, Ph.D., M.P.H., from the University of Florida in Gainesville, and colleagues examined the state-level non-medical exemption rates (for personal or religious beliefs) from school immunization between 1991 and 2004, as well as pertussis incidence between 1986 and 2004 for children younger than 18.

States that allowed exemptions for personal beliefs had higher exemption rates than states only allowing exemptions for religious beliefs, with the mean exemption rate increasing an average of 6 percent a year from 1991 to 2004 for states with personal-belief exemptions. States that more easily granted exemptions had higher exemption rates than those where exemptions were more difficult, with the mean exemption rate increasing an average of 5 percent a year from 1991 to 2004 for states that easily granted exemptions.

States that granted exemptions more easily or allowed exemptions for personal beliefs had a higher incidence of pertussis (incidence rate ratio 1.53 and 1.48, respectively).

"States should examine their exemption policies to ensure control of pertussis and other vaccine-preventable diseases," Salmon and colleagues conclude.

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Health of Bar Workers Improves After Smoking Ban

Respiratory function, inflammation, quality-of-life scores improve in bar workers in Scotland

Since Scotland banned smoking in public places, bar workers have shown improvements in respiratory function and inflammation, according to the results of a study published in the Oct. 11 issue of the Journal of the American Medical Association.

Daniel Menzies, M.B.Ch.B., and colleagues from Ninewells Hospital and Medical School in Dundee, Scotland, examined respiratory function in 77 asthmatic and non-asthmatic non-smoking bar workers in Tayside, Scotland, from February to June 2006. They note that Scotland enacted a ban on smoking in public places on March 26, 2006.

The researchers found that fewer workers had respiratory and sensory symptoms after the ban (79.2 percent before versus 53.2 percent after). There were also significant improvements in spirometry measurements, a drop in serum cotinine levels, a reduction in total white blood cell and neutrophil counts, less airway inflammation and improved quality-of-life scores.

"The comprehensive body of research documenting the serious adverse health effects of passive smoking provides a powerful rationale for prohibiting smoking in all public places," writes Mark D. Eisner, M.D., M.P.H., of the University of California San Francisco, in an accompanying editorial. "The time has come to clear the air."

AbstractFull Text (subscription or payment may be required)Editorial

Lenalidomide Improves Myelodysplastic Syndrome

Some treated patients show complete cytogenetic recovery, and no longer need transfusions

Lenalidomide can promote cytogenetic recovery and reduce or eliminate the need for transfusion due to chronic anemia in some patients with myelodysplastic syndrome associated with 5q31 deletion, according to a report in the Oct. 5 issue of the New England Journal of Medicine.

Alan List, M.D., of the University of South Florida College of Medicine in Tampa, and the Myelodysplastic Syndrome-003 Study Investigators, treated 148 patients with 5q-associated myelodysplastic syndrome with 10 mg of lenalidomide per day for 21 days every four weeks or daily to see if treatment could reduce the requirement for transfusion and suppress the abnormal 5q31 clone.

After 24 weeks, the investigators found that 76 percent of patients had a reduced need for transfusions and 67 percent became transfusion independent. In addition, 62 of 85 evaluated patients had cytogenetic improvement with 38 showing complete cytogenetic recovery. Neutropenia and thrombocytopenia were the most common side-effects associated with treatment interruption.

"We conclude that lenalidomide is effective in lower-risk, transfusion-dependent patients with the myelodysplastic syndrome and a 5q deletion," the authors write. They note that some of their data suggests that lenalidomide may extend survival in higher risk patients as well.

The study was sponsored by Celgene, the manufacturer of lenalidomide, and some of the authors are employees of the company.

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Ranibizumab Slows Macular Degeneration

Two randomized studies show ranibizumab injections improve visual acuity in some patients with age-related macular degeneration

Ranibizumab -- a humanized monoclonal antibody Fab targeting vascular endothelial growth factor A -- prevents visual decay and can even improve visual acuity in patients with neovascular age-related macular degeneration, according to the results of two large, randomized trials published in the Oct. 5 issue of the New England Journal of Medicine.

Philip Rosenfeld, M.D., Ph.D., of the University of Miami, and the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular Age-Related Macular Degeneration (MARINA) Study Group show that only about 6 percent of patients treated with ranibizumab for one year had reduced visual acuity compared to 38 percent of controls. Acuity improved in 33.8 percent of those treated at the highest dose compared with 5 percent of controls.

Similar results were seen in a study by David Brown, M.D., of Methodist Hospital in Houston, and the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in Age-Related Macular Degeneration (ANCHOR) Study Group where ranibizumab was compared to verteporfin therapy. Again, only about 5 percent of ranibizumab-treated patients lost visual acuity after one year compared to 36 percent of verteporfin-treated patients with many in the ranibizumab group showing acuity improvements.

Although the results are "exciting" and may seem "miraculous," a head-to-head study of ranibizumab and bevacizumab with "careful evaluation of an 'induction and follow-up' strategy with either drug are probably the next most useful steps in this field," writes Edwin M. Stone, M.D., Ph.D., in an accompanying editorial.

Both studies were supported by Genentech and Novartis Pharma.

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

Ragweed Vaccine Shows Promise for Allergic Rhinitis

Six-week injection regimen before ragweed season shows positive benefits extending into subsequent seasons

A pilot study of a ragweed pollen vaccine has shown promising long-term results for treatment of allergic rhinitis, according to a report in the Oct. 5 issue of the New England Journal of Medicine.

Peter S. Creticos, M.D., of the Johns Hopkins University School of Medicine in Baltimore, and members of the Immune Tolerance Network Group, conducted a randomized, double-blind, placebo-controlled trial of the vaccine, which consisted of the ragweed pollen Amb a1 conjugated to an immunostimulatory sequence of DNA.

Twenty-five adults who were allergic to ragweed received six weekly injections of the vaccine or placebo before the start of ragweed season. Those randomized to vaccine had better peak-season rhinitis scores and overall quality-of-life scores than the placebo group, and the improvements were still apparent in the following ragweed season. The vaccine was shown to suppress the seasonal increase of Amb a1-specific IgE antibodies.

"This study provides preliminary evidence that a six-injection regimen of [the vaccine] reduces allergic rhinitis symptoms during the ragweed season" and induces "long-lasting immune modulation," the authors conclude. The vaccine "has properties that make it qualitatively superior to standard allergen immunotherapy."

Some of the authors were supported or employed by Dynavax Technologies or Greer Laboratories, which helped in production of the vaccine.

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Sputum Test Quick, Accurate for Drug-Resistant TB

Microscopic-observation drug-susceptibility assay shows greater sensitivity and quicker results

A single microscopic-observation drug-susceptibility (MODS) assay of a sputum sample provides more sensitive and faster detection of tuberculosis and multi-drug-resistant tuberculosis than conventional methods, according to study findings published in the Oct. 12 issue of the New England Journal of Medicine.

David A.J. Moore, M.D., of the Centre for Clinical Tropical Medicine at Imperial College London in the U.K., and colleagues tested the MODS assay in three target groups of Peruvian patients: unselected patients with suspected tuberculosis, prescreened patients at high risk for tuberculosis or multi-drug-resistant tuberculosis, and unselected hospitalized patients infected with HIV.

The researchers found that 401 (10.7 percent) of 3,760 sputum samples tested positive for Mycobacterium tuberculosis. They found that MODS had a greater sensitivity (97.8 percent) compared to automated mycobacterial culture and Lowenstein-Jensen culture (89 and 84 percent, respectively) and a more rapid median time to culture positivity (seven days, compared with 13 and 26 days, respectively).

"The establishment of microbiology laboratories in countries with a high prevalence of tuberculosis and growing rates of drug-resistant tuberculosis should become one of the urgent priorities in the global fight against tuberculosis epidemics, especially in countries with limited resources," state the authors of an accompanying editorial. "The MODS technique may well move this process forward."

AbstractFull Text (subscription or payment may be required)Editorial

Weight Maintenance Program Helps Dieters Keep Weight Off

Program increases daily self-weighing and cuts 18-month weight gain compared to control

A daily self-regulated weight management program seems to help those who recently lost weight keep the pounds off, according to a report in the Oct. 12 New England Journal of Medicine.

Since many successful dieters eventually regain their weight, Rena R. Wing, Ph.D., of Brown Medical School in Providence, R.I., and colleagues developed and tested a weight management program that involved face-to-face or Internet-based counseling and the use of a color-zoned scale. The study included 314 participants who lost an average of 19.3 kg within the past two years and who were assigned either to a control group that received a quarterly newsletter, a group that received face-to-face intervention, or a group that received Internet-based intervention. The two latter groups emphasized daily self-weighing and self-regulation.

After 18 months, the face-to-face study group gained an average of 2.5 kg, while the Internet-based and control groups gained 4.7 kg and 4.9 kg, respectively. Both interventions increased daily self-weighing and helped reduce the number of participants regaining 2.3 kg or more.

"As compared with receiving quarterly newsletters, a self-regulation program based on daily weighing improved maintenance of weight loss, particularly when delivered face-to-face," the authors write. "Future studies should examine ways to refine these interventions in order to improve their efficacy."

Some of the authors have received consulting or lecturing fees from Sanofi, Pfizer or Unilever.

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Atypical Antipsychotics Don't Help Alzheimer Patients

Study shows high intolerability, minimal clinical benefit of atypical drugs for treatment of Alzheimer disease outpatients

Adverse side effects outweigh the clinical benefits of second-generation atypical antipsychotics for treatment of psychosis, aggression or agitation in patients with Alzheimer disease, according to the results of a 42-center, double-blind, placebo-controlled trial published in the Oct. 12 New England Journal of Medicine.

Lon S. Schneider, M.D., from the University of Southern California Los Angeles, and members of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study group compared the benefits of the atypical antipsychotic drugs olanzapine, quetiapine and risperidone, with a placebo in treating Alzheimer disease outpatients.

After 36 weeks, the investigators found no differences in treatment outcome for any of the drugs compared with the control, which was measured by the time to discontinuation of treatment for any reason. In fact, the time to discontinuation of treatment for reasons of patient intolerability favored the placebo. Although more patients treated with the antipsychotics showed improvement by Clinical Global Impression of Change scale measures, the differences were not significant.

An accompanying editorial commends the study for using "real-world" clinical events, noting that the study "is an exemplar of the clinical trial's revolutionary role in shaping therapeutics" and "a model for how to spend our taxes on research, particularly now that taxes also pay for prescriptions."

Several drug companies provided medications for the study.

AbstractFull Text (subscription or payment may be required)Editorial

Childhood Cancer Survivors Have Lifelong Health Problems

Nearly three-fourths of survivors have chronic health conditions as adults

Most survivors of childhood cancer experience additional chronic and life-threatening conditions in adulthood, according to a report in the Oct. 12 issue of the New England Journal of Medicine. Monitoring survivors should be an important part of their overall care, the authors suggest.

In the study, Kevin C. Oeffinger, M.D., of Memorial Sloan-Kettering Cancer Center in New York City, and members of the Childhood Cancer Survivor Study calculated the frequency of chronic conditions in 10,397 childhood cancer survivors and 3,034 of their siblings.

Overall, 62 percent of survivors had one or more chronic health conditions compared with about 37 percent of siblings, while cancer survivors had more than five times as many severe, life-threatening or disabling conditions -- such as major joint replacement and congestive heart failure -- as siblings (27.5 percent and 5.2 percent, respectively). Those who had bone or central nervous system tumors and those treated with chest irradiation, with or without chemotherapy, were at greatest risk for severe or multiple conditions.

"Thirty years after a diagnosis of cancer, almost three-fourths of survivors have a chronic health condition, more than 40 percent have a serious health problem, and one-third have multiple conditions," the authors write. "The incidence of health conditions reported by this population increases with time and does not appear to plateau."

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Misoprostol Can Reduce Acute Postpartum Hemorrhage

Stomach ulcer drug can reduce maternal mortality in developing countries

Oral administration of misoprostol immediately after childbirth significantly reduces the rate of acute postpartum hemorrhage in low-resources settings, according to a report published in the Oct. 7 issue of The Lancet.

Stacie E. Geller, Ph.D., of the University of Illinois at Chicago, and colleagues conducted a placebo-controlled trial of 1,620 women in rural India, in which 812 received oral misoprostol and 808 received placebo after delivery. The primary outcome of acute postpartum hemorrhage was defined as blood loss of at least 500 mL within the first two hours after delivery.

The drug reduced the rate of acute postpartum hemorrhage by almost half, from 12 percent to 6.4 percent, and reduced the rate of severe acute postpartum hemorrhage from 1.2 percent to 0.2 percent. It was also associated with a reduction in mean postpartum blood loss from 262.3 mL to 214.3 mL. However, among the misoprostol group there was a higher rate of chills and fever compared with those in the control group.

"Our results show that oral misoprostol is safe, effective and inexpensive for women giving birth in low-resources settings, and is currently the only available pharmacological option for preventing postpartum hemorrhage and reducing postpartum blood loss in these communities," the authors conclude.

AbstractFull Text (subscription or payment may be required)Editorial

Complications Linked to Weight Gain Between Pregnancies

Even modest weight gain can increase risk for adverse outcomes in second pregnancy

Gaining weight between a first and second pregnancy is likely to raise a woman's risk for adverse outcomes during the second, according to study findings published in the Sept. 30 issue of The Lancet. The results suggest a causal relationship between obesity and pregnancy complications.

To determine if temporal changes in weight affects the risk for adverse pregnancy outcomes, Eduardo Villamor, M.D., of Harvard School of Public Health in Boston, and Sven Cnattingius, M.D., from the Karolinska Institute in Stockholm, Sweden, measured body mass index (BMI) change and pregnancy complications in a population of 151,025 Swedish women having two pregnancies between 1992 and 2001.

The investigators found that women gaining three or more BMI units between their pregnancies were at increased risk for preeclampsia (adjusted odds ratio, 1.78), gestational hypertension (1.76), gestational diabetes (2.09), Caesarean delivery (1.32), stillbirth (1.63), and large-for-gestational-age birth (1.87). The associations were linear and remained even if BMIs during both pregnancies were within the healthy range.

The findings "should lead to a call for more randomized trials of weight loss interventions before pregnancy, as well as weight loss postpartum," according to a comment by Aaron Caughey, M.D., from the University of California San Francisco. "With the recent sustained increase in obesity, particularly in the developed world, such interventions are likely to affect not only future pregnancy outcomes but also long-term outcomes in women's health."

AbstractFull Text (subscription or payment may be required)Editorial

Prior ICU Occupants Pass on Antibiotic-Resistant S. aureus

Use of room by MRSA-positive or VRE-positive patients raises odds of infection for next occupant by 40 percent

Patients with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) can increase the odds of infecting subsequent users of their rooms in intensive care units by 40 percent, according to a report in the Oct. 9 issue of the Archives of Internal Medicine.

Susan S. Huang, M.D., M.P.H., of Brigham and Women's Hospital and Harvard Medical School in Boston, and colleagues conducted a retrospective cohort study of 11,528 ICU stays involving patients who were screened on admission and then weekly for MRSA and VRE. The study compared the odds of picking up either infection in a room previously occupied by an infected patient compared with admission to a room previously occupied by an MRSA- or VRE-negative patient.

MRSA was acquired by 3.9 percent of patients in rooms with previous MRSA patients, compared to 2.9 percent in rooms with previous MRSA-negative patients. For those in rooms previously occupied by VRE-positive or VRE-negative patients, the odds of infection were 4.5 percent and 2.8 percent, respectively. Previous occupants were a minor contributor to infection, accounting for 5.1 percent of all MRSA cases and 6.8 percent of all VRE cases. But the longer a patient stayed in the ICU, the higher the risk of acquiring MRSA or VRE.

The findings strongly suggest "a role for environmental contamination, despite room cleaning methods that exceeded national standards," the authors conclude.

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FDA Needs 'Sweeping Changes' to Safely Regulate Drugs

Regulatory body lacks legal clout and is too close to big drug companies, critics warn

The U.S. Food and Drug Administration needs to undergo radical change to effectively regulate drug safety, according to a special article in the Oct. 9 issue of the Archives of Internal Medicine.

Curt D. Furberg, M.D., Ph.D., of Wake Forest University School of Medicine in Winston-Salem, N.C., and colleagues highlight major problems with the current FDA structure that include faulty pre-approval study design that results in serious adverse effects going undetected, massive under-reporting of adverse events once drugs reach the market, and lax monitoring of manufacturers' commitments to provide post-study safety data.

"The FDA lacks authority to pursue sponsors who violate regulations and ignore post-marketing safety study commitments," the authors write. "The public increasingly perceives the FDA as having become too close to the regulated pharmaceutical industry; the FDA's safety oversight structure is suboptimal; and the FDA's expertise and resources in drug safety and public health are limited."

The paper makes five recommendations to Congress that would give the FDA more legal powers to pursue violators, provide extra funding for safety operations, mandate reorganization of the body, broaden the range of safety experts, and authorize a conditional drug approval policy.

The authors are current or former members of the FDA Drug Safety and Risk Management Advisory Committee.

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Undiagnosed Stroke Symptoms Common, Especially in Blacks

Findings suggest aggressive stroke prophylaxis could be beneficial

Undiagnosed stroke symptoms are common in the general U.S. population, with a higher prevalence among blacks and those with lower incomes, according to study findings published in the Oct. 9 issue of the Archives of Internal Medicine.

Virginia J. Howard, M.S.P.H., of the University of Alabama at Birmingham, and colleagues analyzed data from a randomly sampled national cohort of 18,462 people with no reported history of stroke or transient ischemic attack. The mean age of the cohort was 65.8 years, 51 percent were female and 41 percent were black.

There was a 17.8 percent prevalence of one or more stroke symptoms. For sudden painless hemibody weakness, the prevalence was 5.8 percent, while 8.5 percent experienced sudden hemibody numbness, 4.6 percent sudden painless loss of vision and 3.1 percent sudden hemifield visual loss. Sudden inability to understand speech affected 2.7 percent, and 3.8 percent experienced sudden inability to speak.

Blacks had a higher prevalence of stroke symptoms compared with white participants, and rates were also higher among those with lower income, lower education and fair-to-poor perceived health status.

"Targeted education on the warning signs of stroke and risk factor reduction efforts for individuals who report stroke symptoms may be helpful in improving early recognition and in the prevention of stroke," the authors conclude.

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Four Care Standards Prolong Hemodialysis Patients' Lives

Seven percent of those getting highest-quality care die, versus 29 percent without quality care

Hemodialysis patients treated according to four quality standards for the care of patients with end-stage renal disease are less likely to die or go to the hospital than those whose care reaches no such standards, researchers report in the Oct. 3 issue of the Annals of Internal Medicine.

Michael V. Rocco, M.D., of Wake Forest University School of Medicine in Winston-Salem, N.C., and colleagues evaluated deaths and hospitalizations involving 15,287 long-term hemodialysis patients. Clinical care targets included threshold levels of serum albumin, hemoglobin and urea, as well as fistula use.

The researchers found that one in five patients died and more than half went to the hospital within a year. Treatment for only seven percent of patients met four quality care standards; care for six percent of patients met no standards.

Seven percent of patients whose care reached four quality standards died, versus 29 percent meeting none. Patients with care meeting no targets were 4.6 times more likely to die than those reaching four targets.

"In patients receiving long-term hemodialysis, meeting multiple clinical measure targets is associated with a decrease in hospitalization and mortality rates," the authors conclude.

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Psychiatry Team Doesn't Improve Depression Outcome

Patients do no better with intervention than those who had standard care

Depressed patients who are treated by a primary care physician aided by a support team including a psychiatrist and nurse are more likely to be satisfied with care and to receive antidepressants, but these patients are no more likely to have an improvement in depression than patients whose doctors don't have the extra support, according to a report in the Oct. 3 issue of the Annals of Internal Medicine.

Steven K. Dobscha, M.D., of Portland Veterans Affairs Medical Center in Portland, Ore., and colleagues evaluated the outcomes in 189 depressed patients who were treated by clinicians along with a decision support team and compared those patients with 186 patients who had usual care. The support team phoned the patient, conducted education, reviewed records monthly and issued a progress report to the clinician every three months. The patients were assessed for changes in depression scores at six and 12 months.

Although depression scores improved for both groups, the decision support intervention was not clinically or significantly more effective than usual care. At one year, more patients in the intervention group reported increased satisfaction, had seen a mental health specialist at least once and received antidepressants compared with those in usual care.

"Decision support improved processes of care but not depression outcomes. More intensive care management or specialty treatment may be needed to improve depression outcomes," the authors conclude.

AbstractFull Text

Failure to Order Test Common Mistake in Malpractice Claims

Individual and system factors all contribute to errors in ambulatory setting

A failure to order an appropriate diagnostic test is the most common mistake that results in harm to patients in the ambulatory care setting, although multiple breakdowns and individual and system factors play a role, according to a review of malpractice claims in the Oct. 3 issue of the Annals of Internal Medicine.

Tejal K. Gandhi, M.D., of the Brigham and Women's Hospital and Harvard School of Public Health in Boston, and colleagues retrospectively reviewed 307 closed malpractice claims alleging delayed or missed diagnosis in an ambulatory setting. The claims involved four malpractice insurance companies.

Overall, 181 claims (59 percent) alleged harmful diagnostic errors, and 106 of these were linked to serious harm, with 55 of those fatal. At 59 percent, cancer was most often involved, most frequently breast cancer (44 claims) and colorectal cancer (13 claims). Failure to order correct diagnostic tests caused 55 percent of breakdowns; an inadequate follow-up accounted for 45 percent; lack of adequate history and inadequate physical examination were linked with 42 percent of claims; and incorrect interpretation of the tests, 37 percent. Failures in judgment, memory or vigilance, and knowledge were among the most common factors for errors.

"Like other medical errors, diagnostic errors are multi-factorial. They arise from multiple process breakdowns, usually involving multiple providers. The results highlight the challenge of finding effective ways to reduce diagnostic errors as a component of improving health care quality," the editors note.

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Patients' Insurance Status Affects Clinical Decision-Making

Physicians frequently alter clinical management to take insurance into account

Physicians frequently take into account a patient's insurance status during the course of clinical decision-making and management, according to a study published in the September/October issue of the Annals of Family Medicine.

David S. Meyers, M.D., of the Agency for Healthcare Research and Quality in Rockville, Md., and colleagues conducted a survey of 25 primary care physicians in metropolitan Washington, D.C., who completed a brief questionnaire after seeing each patient during two half-day sessions.

In all, 88 percent of participants made at least one change to clinical management because of the insurance status of the patient. Out of 409 patient encounters, they made changes in 99 cases (24.2 percent). The most affected were uninsured patients: changes were made in 43.5 percent of uninsured patients' cases, versus 29.5 percent for publicly insured patients and 18.7 percent for privately insured patients. Insurance issues were discussed with patients in 62.6 percent of visits.

"Additional research is needed to understand the effect of these changes on patient health and to assist both doctors and patients in enhancing the quality of care delivered within the constraints of the current insurance system," the authors conclude.

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Drug Company Reviews Should Be Read with Caution

Industry-supported reviews are more likely than independent research to reach favorable conclusions

Drug reviews supported by the pharmaceutical industry are less transparent and more likely to reach a favorable conclusion compared with independent research, and as such should be read with caution, according to a report published online Oct. 6 in BMJ.

Peter Gotzsche, M.D., of the Nordic Cochrane Center in Copenhagen, Denmark, and colleagues conducted a systematic review of pairs of meta-analyses that were published less than two years apart and studied the same drugs for the same disease. Of the 24 studies that were matched with reviews undertaken by the independent Cochrane Collaboration, eight were supported by the pharmaceutical industry, seven were unsupported or were supported by non-industry sources and nine had undeclared support.

The Cochrane reviews more often took into consideration the potential for bias, and none of the Cochrane reviews unreservedly recommended the drug under review, compared with seven out of the seven industry reviews that reached a conclusion about the drug in question. Studies that were unsupported or had not-for-profit support reached similarly cautious conclusions as the Cochrane reviews.

"Industry-supported reviews of drugs should be read with caution as they were less transparent, had few reservations about methodological limitations of the included trials and had more favorable conclusions than the corresponding Cochrane reviews," the authors conclude.

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Physical Activity Doesn't Prevent Obesity in Preschoolers

Improvements in motor skills may have longer-term health benefits

Physical activity does not have an impact on obesity levels among preschool children but the benefits it confers in terms of motor and movement skills may help to foster an increase in activity levels and therefore have long-term benefits, according to a study published online Oct. 6 in BMJ.

John J. Reilly, Ph.D., of the University of Glasgow, and colleagues conducted a study of 545 preschoolers in 36 nurseries in Glasgow, Scotland, who were randomized to participate in an enhanced physical activity program of three 30-minute sessions a week over 24 weeks, as well as education to boost home-based physical activity, or a control group with no intervention. The main outcome was body mass index.

When body mass index was measured at six and 12 months, the intervention had no impact, nor did it reduce sedentary behavior. However, participants in the intervention group performed significantly better than their control counterparts in terms of movement skills. In the long-term, this could foster greater confidence in carrying out physical activities, the report indicates.

"Time in nursery is limited and there is pressure on the curriculum. Successful interventions to prevent obesity in early childhood may require changes not just at nursery, school and home but in the wider environment. Changes in other behavior, including diet, may also be necessary," the authors conclude.

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Twins and Singletons Evenly Matched Academically

Ninth-grade test scores comparable although twins weigh slightly less at birth

Although previous studies have suggested otherwise, twins have academic test scores similar to singletons when tested in the ninth grade, researchers report in the Sept. 29 Online First edition of BMJ.

Kaare Christensen, M.D., Ph.D., of the University of Southern Denmark in Odense, and colleagues compared ninth-grade test scores, birth weight and other factors in 3,411 twins and 7,796 singletons born between 1986 and 1988 in Denmark.

The researchers found that both groups tested normally in ninth grade, with a mean test score of 8.02 for both groups, and a 1.05 standard deviation for twins versus 1.06 for singletons. Newborn twins generally weighed almost a kilogram (908 grams) less than singletons.

The similarity in test scores held firm after researchers adjusted for factors such as parents' age, and the gestational age and weight of newborns. Although the researchers found a significant link between birth weight and test scores, the standard deviation in test scores was only 0.06 to 0.12 for each additional kilogram at birth.

"Although older cohorts of twins have been found to have lower mean IQ scores than singletons, twins in recent Danish cohorts show similar academic performance in adolescence to that of singletons," the authors write.

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Breast-Feeding Does Not Boost Offspring's IQ

Maternal IQ explains breast-feeding's effect on a child's intelligence

Breast-feeding does not affect a child's intelligence after correction for maternal IQ, according to the results of the largest-ever study to explore this connection. The findings were published online Oct. 4 in BMJ.

Geoff Der, Ph.D., of the Medical Research Council Social and Public Health Sciences Unit in Glasgow, Scotland, and colleagues found that when they controlled for maternal intelligence, most of the effect that breast-feeding was thought to have on a child's intelligence disappeared. They conducted a prospective study among 5,475 children from 3,161 mothers, a sibling-pairs analysis, and a meta-analysis.

One standard deviation advantage in maternal IQ score more than doubled a newborn's chance of being breast-fed. Before adjustment, breast-feeding was associated with a four-point increase in mental ability, but controlling for maternal intelligence accounted for most of this effect. When all confounders (including level of cognitive stimulation at home, mother's educational attainment and age at child's birth, birth order and finances) were considered, the effect of breast-feeding on intelligence was "small" and "non-significant."

However "breast-feeding remains an 'an unequalled way of providing ideal food for the healthy growth and development of infants,'" the authors conclude.

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Corticosteroid Injections Don't Help Tennis Elbow in Long Run

Study shows short-term benefits of injections lost after 52 weeks

Tennis elbow, which affects up to 3 percent of the general population and 15 percent of workers in at-risk industries, is better treated with physiotherapy than with corticosteroid injections, according to a report published online Sept. 29 in BMJ.

Bill Vicenzino, Ph.D., of the University of Queensland in Australia, and colleagues randomized 198 participants with a clinical diagnosis of tennis elbow to eight sessions of either corticosteroid injections, physiotherapy or a "wait and see" approach, and followed their improvement at six weeks and 52 weeks.

In the short term, 78 percent of patients receiving corticosteroid injections reported functional improvement compared to 65 percent who received physiotherapy and only 27 percent in the "wait and see" group. However, the researchers found that the recurrence rates were highest (72 percent) and recovery was delayed over the long term in patients receiving corticosteroid injections. No difference was seen at 52 weeks between the physiotherapy and "wait and see" groups.

"The significant short-term benefits of corticosteroid injection are paradoxically reversed after six weeks, with high recurrence rates, implying that this treatment should be used with caution in the management of tennis elbow," the authors write. The "poor overall performance with corticosteroid injections should be taken under consideration by both patients and their doctors in the management of tennis elbow."

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Walnuts May Help Reverse Effects of High-Fat Meal

Walnuts and olive oil protect arterial endothelial cells; only walnuts improve vasoactivity

Walnuts improve arterial flow-mediated dilation (FMD) immediately after a high-fat meal, and walnuts and olive oil acutely conserve protective arterial endothelial cells after such a meal, according to a report published online Oct. 9 in the Journal of the American College of Cardiology.

Berenice Cortes, B.S., of the Universitat Autonoma de Barcelona in Spain, and colleagues analyzed the effect of walnuts and olive oil on postprandial endothelial dysfunction in 12 normolipidemic volunteers and 12 hypercholesterolemia patients. Both groups ate two high-fat meals (35 percent saturated fat) to which 25 grams of olive oil or 40 grams of walnuts were added.

Ultrasound measurements of the brachial artery endothelial function showed postprandial FMD was impaired after the olive oil meal in both groups. However, walnuts did not change FMD in the healthy subjects, and improved it in 24 percent of the hypercholesterolemic group. Blood testing showed the concentrations of inflammatory cytokines and adhesion molecules decreased after both meals.

"Adding walnuts to a high-fat meal acutely improves FMD independently of changes in oxidation, inflammation, or plasma asymmetric dimethylarginine. Both walnuts and olive oil preserve the protective phenotype of endothelial cells," the authors conclude.

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Sirolimus-Eluting Stents Best for Coronary Lesions

Lower rates of major adverse cardiac events than with paclitaxel-eluting stents

Sirolimus-eluting stents (SES) result in lower rates of major adverse cardiac events compared with paclitaxel-eluting stents (PES), according to a report in the Oct. 3 issue of the Journal of the American College of Cardiology.

Francesco Saia, M.D., Ph.D., of the University of Bologna in Italy, and colleagues analyzed data from 1,676 patients with de novo coronary lesions whose treatment solely entailed the use of drug-eluting stents (992 with SES and 684 with PES). The study compared the two types of stents in terms of major adverse cardiac events, which included death, myocardial infarction and target vessel revascularization.

Among the cohort, 29 percent also had diabetes, 23 percent had previous history of myocardial infarction and 9 percent had poor left ventricular function. One year after treatment, the incidence of major adverse cardiac events was 9.2 percent among those treated with SES, compared with 14.1 percent for those treated with PES. The rate of target vessel revascularization was 5 percent for SES and 10 percent for PES. However, rates of death and myocardial infarction were similar for the two treatment groups.

"In this large and complex real-world population, the use of SES reduced the one-year incidence of adverse cardiac events as compared with PES, mainly by decreasing the need for repeat revascularizations," the authors conclude.

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Polyunsaturated Fats May Help Heart Failure Patients

Dietary supplementation with PUFAs improves bradycardia in stable congestive heart failure

Heart failure patients who take supplemental polyunsaturated fatty acids, or PUFAs, have an improvement in arterial baroreflex function in cardiac and peripheral vasculature as well as heart rate variability, according to a report published online Oct. 9 in the Journal of the American College of Cardiology.

Alberto Radaelli, M.D., of the Universita di Milano-Bicocca in Milan, Italy, and colleagues compared the effects of PUFA dietary supplementation (2 grams/day) or a placebo for four months in 25 patients with chronic post-myocardial infarction systolic heart failure, all of whom were taking beta-blockers or angiotensin-converting enzyme inhibitors. The researchers evaluated beat-to-beat blood pressure, R-R interval and baroreceptor reflexes measured by bradycardic and depressor responses to neck suction and the alpha "spontaneous" baroreflex sensitivity index.

Only those patients who received PUFA supplementation had increased spontaneous baroreflex sensitivity as well as increased reflex depressor and bradycardic responses to neck suction. The PUFA group also showed significantly increased R-R interval total variance, while the placebo group did not.

"Dietary PUFA supplementation markedly potentiates baroreflex function and enhances heart rate variability in patients with stable congestive heart failure," the authors conclude.

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Source of Ethnic Disparity in Medicare Claims Unclear

Preventive screening discrepancies found between Medicare claims records and patient reports

Ethnic disparities in preventive screening tests are larger when estimated with Medicare claims than patient self-reports, according to a report published Sept. 29 in BioMed Central Health Services Research.

Kevin Fiscella, M.D., and colleagues from the University of Rochester School of Medicine and Dentistry in Rochester, N.Y., evaluated 49,645 patient records of preventive procedures and compared those with the patients' matched Medicare claims. The authors analyzed six preventive procedures: PSA testing, Pap smear testing, influenza vaccination, cholesterol testing, mammography and colorectal cancer tests.

Except for PSA testing, ethnic disparities in the preventive procedures were larger when based on Medicare claims compared to patient self-reports. After demographic and health status adjustments, the investigators found that minorities were more likely to report preventive procedure receipts without a submitted Medicare claim.

"This study shows that estimates of racial/ethnic disparities, across a variety of preventive care procedures, vary depending on whether self-report or claims are used to assess them. Whether these differences reflect biases in participant report or in billing claims is unclear. These competing explanations have profoundly different policy implications, and thus warrant careful study. Future monitoring of disparities in screening will require more careful distinction of screening from diagnostic uses of preventive procedures," the authors conclude.

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Family History of Lung Cancer Increases Lung Cancer Risk

Risk higher for women and non-smokers

Having a family history of lung cancer increases the risk of developing lung cancer, particularly for women and non-smokers, researchers report in the October issue of Chest.

Manami Inoue, M.D., Ph.D., from the National Cancer Center in Tokyo, Japan, and colleagues examined the association between lung cancer and a family history of the disease in 102,255 Japanese adults aged 40 to 69 years. After 13 years of follow-up, they identified 791 new cases of lung cancer.

The researchers found that having a first-degree relative with lung cancer, but not other cancers, increased lung cancer risk by nearly twofold (hazard ratio, 1.95), particularly for squamous cell carcinoma (HR, 2.79). Women were at higher risk than men (HR, 2.65 versus 1.69), and those who had never smoked were at higher risk than current smokers (HR, 2.48 versus 1.73). There was no link, however, between a family history of overall cancer and increased risk of lung cancer.

"These results suggest that those with a family history of lung cancer are more likely to acquire lung cancer themselves," Inoue and colleagues conclude.

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Intranasal Flu Vaccine May Help Patients with COPD

There may be some benefit to adding intranasal vaccine to conventional flu shot

A combination of an intranasal influenza vaccine and a conventional intramuscular flu shot may improve airflow obstruction and functional status in patients with chronic obstructive pulmonary disease (COPD) who develop acute respiratory illness during flu season, according to a study in the October issue of Chest.

Geoffrey J. Gorse, M.D., from St. Louis University Health Sciences Center, and colleagues examined the effect of influenza vaccination on the health of 2,215 veterans with COPD. All patients were vaccinated with a trivalent inactivated influenza virus vaccine and were randomly assigned to also receive either an intranasal, live attenuated influenza virus vaccine or a placebo.

The researchers found that acute respiratory illness, of which some cases were caused by influenza infection, was associated with airflow obstruction, worse lung disease severity scores and more frequent hospitalization. Those who had received the combination of vaccines, or who did not become ill, had better lung disease severity scores at the end of the study.

"Acute respiratory illness was associated with increased health care utilization and obstruction to airflow, and worse functional status and well-being," Gorse and colleagues conclude. "At the end of the study, receipt of [the intranasal vaccine] was associated with improvement, and acute respiratory illness was associated with worsening in functional status and well-being."

The study was supported by Aviron, now MedImmune Vaccines, Inc., manufacturer of the intranasal trivalent, live-attenuated, cold-adapted influenza virus vaccine.

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Gastroesophageal Reflux May Worsen COPD

Rate of exacerbations twice as high as in those with chronic obstructive pulmonary disease alone

Patients with gastroesophageal reflux disease (GERD) and chronic obstructive pulmonary disease (COPD) have twice the rate of COPD exacerbations as patients with COPD alone, according to the results of a study published in the October issue of Chest.

Kenneth J. Vega, M.D., and colleagues from the University of Florida Health Science Center in Jacksonville examined the effect of GERD on COPD in 86 patients diagnosed with COPD. GERD was assessed through the Mayo Clinic GERD questionnaire and was considered clinically significant if heartburn and/or acid regurgitation occurred on a weekly basis.

The researchers found that 37 percent of patients had symptoms of GERD. These patients had a twofold higher rate of COPD exacerbations (3.2/year versus 1.6/year). Those with and without GERD did not differ in their mean forced expiratory volume in one second percentage predicted, according to the report.

"The presence of gastroesophageal reflux symptoms appears to be associated with increased exacerbations of COPD," Vega and colleagues conclude.

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

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