A summary of the "must-read" articles from the journals in that pile on your desk.
No Interaction Seen Between Clopidogrel and Statins
Secondary analysis of CHARISMA study suggests that co-administration of two drugs is safe
Contrary to concerns that certain statins may reduce the effectiveness of clopidogrel because both are metabolized by CYP3A4, there is no evidence that the drugs interact, according to a report in the July 24 issue of the Journal of the American College of Cardiology.
Jacqueline Saw, M.D., of the University of British Columbia in Vancouver, Canada, and colleagues performed a secondary analysis of the CHARISMA study, in which 10,078 of the 15,603 enrollees received clopidogrel and a statin, some that were metabolized by CYP3A4 (atorvastatin, lovastatin, simvastatin) and some not (pravastatin, fluvastatin).
After a median follow-up of 28 months, the researchers found that rates for the primary end point -- a composite of myocardial infarction, stroke, or cardiovascular death -- were similar among patients taking a CYP3A4-metabolized statin and clopidogrel (5.9 percent statin/clopidogrel versus 6.6 percent statin/placebo) and other statins (5.7 percent statin/clopidogrel versus 7.2 percent statin/placebo).
"Data currently available suggest that clopidogrel response variability is clinically more important than the possibility of interaction with other CYP3A4-metabolized drugs," state the authors of an accompanying editorial. "Therefore, clinicians should continue to prescribe clopidogrel and statins where clinically indicated and disregard selecting statins on the basis of CYP3A4 metabolism. Nevertheless, prospective studies are still required to fully elucidate the potential clinical impact of coadministration of CYP3A4-metabolized drugs, including clopidogrel and lipophilic statins."
Modified Antibody Effective in Treating Crohn's Disease
Certolizumab pegol binds tumor necrosis factor-alpha
The experimental drug certolizumab pegol, a pegylated antibody fragment that binds tumor necrosis factor-alpha (TNF-α), is more effective than placebo in treating patients with Crohn's disease, according to two studies in the July 19 issue of the New England Journal of Medicine.
In the first study, William J. Sandborn, M.D., from the Mayo Clinic in Rochester, Minn., and colleagues randomized 662 adults with moderate-to-severe Crohn's disease to either placebo or 400 mg certolizumab pegol at weeks 0, 2 and 4, then every four weeks to week 24. After six weeks, the response rate was significantly higher in the certolizumab pegol group (35 versus 27 percent). Remission rates were similar in both groups.
In the second study, Stefan Schreiber, M.D., from Christian Albrechts University in Kiel, Germany, and colleagues treated 668 adults with moderate-to-severe Crohn's disease with 400 mg certolizumab pegol at weeks 0, 2 and 4. Patients who responded were then randomized to placebo or certolizumab every four weeks to week 24. The researchers found that 64 percent of patients initially responded, which was maintained until the end of the study in more patients who received certolizumab pegol and whose C-reactive protein level was at least 10 mg/L (63 versus 36 percent).
The "evidence points toward the conclusion that certolizumab is an effective therapy for patients with Crohn's disease," according to an accompanying editorial. If the drug is approved, it is unlikely that anti-TNF-α agents will be compared in head-to-head trials, so "choice of therapy will probably be driven by other factors, such as perceived relative effectiveness, economics, and convenience for patients."
Both studies were partially supported by a grant from UCB Pharma.
Drug Combo Boosts Risk in Peripheral Arterial Disease
Antiplatelet plus anticoagulants has no benefit, and increases bleeding
Patients with peripheral arterial disease who take an oral anticoagulant in combination with an antiplatelet drug do not benefit in terms of cardiovascular events and are more likely to experience life-threatening bleeding, including hemorrhagic stroke, than patients on antiplatelet therapy alone. The findings are published in the July 19 issue of the New England Journal of Medicine.
Sonia Anand, M.D., Ph.D., of McMaster University in Hamilton, Ontario, Canada, and colleagues from the Warfarin Antiplatelet Vascular Evaluation (WAVE) Trial followed 2,161 patients with peripheral arterial disease for up to 3.5 years (mean age 64 years; 73.6 percent men). About half of the patients took an antiplatelet agent (aspirin, ticlopidine or clopidogrel) and an oral anticoagulant (warfarin or acenocoumarol), while the other half took antiplatelets alone.
There were no differences in the rate of myocardial infarction, stroke, severe ischemia or death from cardiovascular causes in the two groups. However, those taking a combination of drugs had higher incidences of minor and moderate, as well as life-threatening, bleeding (4.0 versus 1.2 percent; relative risk, 3.41).
"The totality of evidence shows clearly that the addition of an anticoagulant to an antiplatelet drug results in increased rates of bleeding complications," writes Emile R. Mohler III, M.D., of the University of Pennsylvania School of Medicine in Philadelphia, in an accompanying editorial.
Sperm Injection for IVF Increased Sharply Over Decade
Data suggest technique is becoming more common in cases without male-factor infertility issues
The use of intracytoplasmic sperm injection (ICSI) during in vitro fertilization rose steeply between 1995 and 2004, even though diagnoses of infertility attributable to male-factor issues stayed steady during that period, researchers report in the July 19 issue of the New England Journal of Medicine.
Tarun Jain, M.D., of the University of Illinois at Chicago College of Medicine, and Ruchi S. Gupta, M.D., of the Feinberg School of Medicine at Northwestern University in Chicago, analyzed data collected from fertility centers throughout the United States and reported to the U.S. Centers for Disease Control and Prevention.
The researchers found that the use of ICSI rose from 11 percent of in vitro fertilization cycles in 1995 to 57.5 percent in 2004. However, diagnoses of male-factor infertility remained stable between 1999 and 2004, suggesting that ICSI is increasingly being used in cases that aren't attributed to male factors. In addition, they found that ICSI is more common for cases not attributed to male factors in states that mandate health insurance coverage for in vitro fertilization.
Other research has found that "clinical outcomes are not improved with ICSI for infertility that is not attributed to male-factor conditions," the authors point out. Also, ICSI has been associated with increased risk of imprinting disorders and serious congenital anomalies.
Gene Variant Associated with Restless Legs Syndrome
Variant also found in people with periodic movements in sleep without disorder
Researchers have identified a gene variant strongly associated with periodic limb movements in sleep and restless legs syndrome, according to a report published online July 18 in the New England Journal of Medicine.
Kari Stefansson, M.D., from deCODE Genetics in Reykjavik, Iceland, and colleagues examined the whole genome for gene variants associated with restless legs syndrome in 306 Icelandic patients with objectively documented evidence of the disorder and 15,633 controls.
The investigators found a highly significant association between restless legs syndrome and a common variant in an intron of the BTBD9 gene on chromosome 6p21.2 (odds ratio, 1.8), which was validated in additional Icelandic and American samples. The population attributable risk of developing the disorder was about 50 percent in individuals with the variant. The variant was also associated with periodic movements in sleep in patients without the disorder (OR, 1.9).
The study "offers hope to patients with periodic limb movements in sleep and restless legs syndrome that the syndrome's pathophysiology will be understood and that such knowledge will lead to additional effective and durable treatments," John W. Winkelman, M.D., Ph.D., from Brigham and Women's Hospital and Harvard Medical School in Boston, writes in an accompanying editorial.
HIV Patients Can Achieve Normal CD4 Cell Counts
Combination antiretroviral therapy that strongly suppresses HIV viral load may be key
In most HIV-positive patients, long-term combination antiretroviral therapy that suppresses HIV viral load to below 50 copies per milliliter may restore CD4 cell counts to levels found in HIV-negative subjects, according to study findings published online July 19 in The Lancet.
Amanda Mocroft, M.D., of the Royal Free and University College London Medical Schools in the United Kingdom, and colleagues studied 1,835 patients with an initial mean CD4 cell count of 204 cells per μL of blood who responded well to combination antiretroviral therapy.
After one year of combination antiretroviral therapy, the researchers found that CD4 cell counts increased an average of 100 cells per μL. During years two through five, cell counts continued to increase at an annual rate of about 50 cells per μL in patients with initial counts below 500 cells per μL and also significantly increased in patients with counts below 200 cells per μL. After three years of therapy, patients with initial counts above 350 cells per μL achieved levels comparable to those of HIV-negative subjects.
"The findings are important because they imply that patients maintaining maximum virological suppression on combination antiretroviral therapy will eventually achieve normal CD4 counts, even those with low baseline CD4 counts," state the authors of an accompanying editorial.
Gene Variant Strongly Linked to Macular Degeneration
Polymorphism in complement gene associated with twofold to threefold increase in risk
A single-nucleotide polymorphism in the C3 complement gene is strongly linked to an increase in the risk of age-related macular degeneration, according to research published online July 18 in the New England Journal of Medicine.
John R.W. Yates, F.R.C.P., of the University of Cambridge in the United Kingdom, and colleagues genotyped 12 single-nucleotide polymorphisms spanning the complement genes C3 and C5 among a group of 446 U.K. subjects with late-stage age-related macular degeneration, and 267 controls. In addition, the researchers genotyped 662 additional subjects with either late-stage macular degeneration or age-related maculopathy.
Patients with a single copy of the rs2230199 (Arg80Gly) polymorphism in the C3 gene, known as C3 fast (C3F), were 1.7 times as likely to have age-related macular degeneration as those without the allele. Subjects with two copies of C3F had 2.6 times the risk. The association with age-related maculopathy fell just short of significance, suggesting that C3F exerts a greater influence as the disease progresses.
The authors estimate that about 20 percent of white populations carry the C3F allele, but the percentage is lower in other groups. "This finding further underscores the influence of the complement pathway in the pathogenesis of this disease," they conclude.
Genome Scan Finds Genes Linked to Heart Disease
Chromosome 9p21.3 had strongest association with coronary artery disease, myocardial infarction
A scan of the human genome has identified several gene variants that are associated with coronary artery disease, according to a study published online July 18 in the New England Journal of Medicine.
Nilesh J. Samani, F.Med.Sci., from the University of Leicester in the United Kingdom, and colleagues scanned the genome of 1,926 patients with coronary artery disease and 2,938 controls from the Wellcome Trust Case Control Consortium. They tried to replicate the findings in 875 patients with myocardial infarction and 1,644 controls from the German Myocardial Infarction Family Study.
The researchers found that gene variants on chromosome 9p21.3, 6q25.1, and 2q36.3 were modestly (unadjusted odds ratios 1.20-1.37) but significantly associated with coronary artery disease in both groups. Combining data from both groups identified four additional variants on chromosomes 1, 10, and 15 that were significantly associated with coronary artery disease in either study.
This and other recent studies "are an important advance in the application of genetics to coronary disease and are likely to represent the leading edge of intense activity in this area," Anthony Rosenzweig, M.D., from Beth Israel Deaconess Medical Center in Boston, writes in an accompanying editorial.
Protocol Improves Survival in Infants with Leukemia
Hybrid treatment for acute lymphoblastic leukemia borrows some elements from acute myeloid leukemia
A new hybrid treatment for acute lymphoblastic leukemia (ALL) that borrows some elements from the treatment of acute myeloid leukemia may improve survival in infants with the disease, according to new data published in the July 21 issue of The Lancet.
Rob Pieters, Ph.D., of Erasmus MC-Sophia Children's Hospital in Rotterdam, the Netherlands, and colleagues evaluated a hybrid regimen in 482 patients under 1 year of age. The infants were arranged in risk order after receiving prednisone pretreatment for seven days. They were then given the hybrid treatment regimen, which involved standard ALL therapy plus the use of cytarabine in low-dose and high-dose sequences and methotrexate.
Overall, 58 percent of the 482 patients who received the hybrid treatment were in complete remission in just over three years. The typical event-free survival for infants with ALL ranges from 17 percent to 45 percent, but in the new study the four-year event-free survival was 47 percent.
Patients who did not do well tended to have rearrangements in the mixed lineage leukemia gene, very high white blood cell counts, developed ALL when they were younger than six months of age and did not respond well to prednisone pretreatment.
"We believe that this hybrid treatment protocol will be used as the standard for continuing international collaborative studies that aim to further improve outcomes for acute lymphoblastic leukemia in infants," the study authors conclude.
Two Drugs Best For Chronic Lymphocytic Leukemia
Combination therapy increases progression-free survival in chronic lymphocytic leukemia
Combining fludarabine and cyclophosphamide increases progression-free survival and complete response rates among patients with chronic lymphocytic leukemia (CLL), when compared to treatments with either fludarabine or chlorambucil alone, researchers report in the July 21 issue of The Lancet.
Daniel Catovsky, F.R.C.P., of the Institute of Cancer Research in Sutton, U.K., and colleagues divided 777 CLL patients into three groups with 196 receiving fludarabine and cyclophosphamide, 194 receiving fludarabine alone and 387 receiving chlorambucil alone.
While there were no significant differences in overall survival among the three groups, progression-free survival was higher in the combination group. Specifically, progression-free survival was 36 percent in the combination group, compared with 10 percent in each of the other two groups.
Moreover, 38 percent of patients in the combination group showed complete response rates. By contrast, 15 percent of patients in the fludarabine group and 7 percent in the chlorambucil group showed complete response rates, the report indicates. Side effects varied between the groups.
"Fludarabine plus cyclophosphamide should now become the standard for chronic lymphocytic leukemia and the basis for new protocols that incorporate monoclonal antibodies," the study authors conclude.
Aliskiren Plus Valsartan Controls Blood Pressure
However, combination therapy may also cause dangerous increase in serum potassium
Aliskiren and valsartan given together at their maximum recommended doses pack a powerful one-two punch against hypertension, resulting in greater reductions than either drug alone, according to a report in the July 21 issue of The Lancet. However, the combination may also cause potentially life-threatening increases in serum potassium.
Suzanne Oparil, M.D., of the University of Alabama at Birmingham, and colleagues divided 1,797 patients with hypertension into four groups. The first group received 150 mg of aliskiren once daily, the second group received 160 mg of valsartan once daily, the third group received a combination of 150 mg of aliskiren and 160 mg of valsartan once daily, and the fourth group received placebo. Patients received these treatments for four weeks, followed by four weeks of double doses.
The group receiving the maximum dose of aliskiren and valsartan experienced a mean drop in sitting diastolic blood pressure of 12.2 mm Hg, compared to a 9 mm Hg drop in the aliskiren group, a 9.7 mm Hg drop in the valsartan group and a 4.1 mm Hg decrease in the placebo group. Adverse events were similar across the groups.
But more patients in the combination group showed transient increases in potassium that could potentially lead to hyperkalaemia and its resulting severe complications, stressed editorialists from the University of Leuven in Belgium. "Because of the potential life-threatening side effects, which require biochemical monitoring, this concept of treatment is unlikely to make it to general practice or even to primary prevention in specialist care," the editorialists write.
Patient Lives Normal Life Despite Thin Cortex
Scans of man in his 40s reveal 'grossly enlarged' cerebral ventricles
A middle-aged man of normal intelligence was found to have grossly enlarged cerebral ventricles and an extremely thin cortex after experiencing a bout of leg weakness at age 44, according to a case study in the July 21 issue of The Lancet.
Lionel Feuillet, M.D., of the Universite de la Mediterranee in Marseille, France, and colleagues report that the man, a married civil servant with two children, complained of mild left leg weakness. Computed tomography and magnetic resonance imaging examinations revealed "massive enlargement of the lateral, third, and fourth ventricles" as well as "a very thin cortical mantle and a posterior fossa cyst."
The patient's previous medical history included an unexplained hydrocephalic episode at 6 months of age, which was treated with a ventriculoatrial shunt. The shunt was revised at age 14 when the patient experienced ataxia and paresis of the left leg. He demonstrated no other abnormalities. Testing indicated an overall IQ of 75, with a verbal IQ of 84 and a performance IQ of 70.
"We diagnosed a non-communicating hydrocephalus, with probable stenosis of Magendie's foramen," the authors conclude. They inserted a ventriculoperitoneal shunt and "the findings on neurological examination became normal within a few weeks. The findings on neuropsychological testing and computed tomography did not change."
Residents' Decreased Duty-Hours May Have Downside
Duty-hour restrictions for residents may increase workload for faculty
Most internal medicine faculty members believe that decreased resident duty-hours have had adverse effects on both residents and faculty, according to a report published in the July 23 issue of the Archives of Internal Medicine.
Darcy A. Reed, M.D., of the Mayo Clinic College of Medicine in Rochester, Minn., and colleagues surveyed 111 key clinical faculty from 39 internal medicine residency programs.
Although 50 percent of the faculty believed that decreased duty-hours had improved the residents' well-being, strong majorities agreed that it had compromised the residents' continuity of care (87 percent), physician-patient relationships (75 percent), education (66 percent) and professionalism (73 percent). Many of them also agreed that the reduced workload for residents had increased their own workload (47 percent), and decreased their satisfaction with teaching (56 percent), ability to develop relationships with residents (40 percent), and overall career satisfaction (31 percent).
"The duty-hour restrictions have improved the well-being of the residents but may be worsening the well-being of faculty members," states the author of an accompanying editorial. "To unravel the key determinants of physician education that lead to safe, responsible, patient-centered, quality health care, considerable research will be needed. In the meantime, transferring responsibility to faculty may lead to faculty burnout and dissatisfaction."
Outpatient Blood Clots Present Public Health Challenge
Nearly three out of four patients who develop venous thromboembolism are in outpatient setting
Outpatients are more likely than inpatients to develop venous thromboembolism, indicating a need for more aggressive anticoagulant prophylaxis, according to a study published in the July 23 issue of the Archives of Internal Medicine.
Frederick A. Spencer, M.D., of McMaster University Medical Center in Hamilton, Ontario, Canada, and colleagues studied 1,897 subjects with a confirmed episode of venous thromboembolism, 73.7 percent of whom developed the condition in an outpatient setting.
The researchers found that major risk factors for venous thromboembolism in an outpatient setting included hospitalization (36.8 percent) or surgery (23.1 percent) within the previous three months, active cancer (29 percent), and a previous venous thromboembolism (19.9 percent). Of the 516 recently hospitalized patients who later developed venous thromboembolism, only 42.8 received anticoagulant prophylaxis during their hospital stay.
"I predict that preventing outpatient venous thromboembolism will be the 'hot button' issue in 2008," states Samuel Z. Goldhaber, M.D., of Brigham and Women's Hospital in Boston, in an accompanying editorial. "We must start collecting relevant data at the time of hospital discharge so that we can provide these vulnerable patients with proper and comprehensive venous thromboembolism prophylaxis. Recognizing the public health threat of outpatient venous thromboembolism and breaking down artificial barriers between outpatient and inpatient venous thromboembolism prophylaxis are vital first steps."
Drinking Soda Associated with Metabolic Syndrome
Study finds drinking diet soda does little to lower risk
Consumption of at least one soda per day is associated with a higher risk of metabolic syndrome in middle-aged adults, according to a report published in the July 31 issue of Circulation: Journal of the American Heart Association.
Ramachandran Vasan, M.D., of Boston University School of Medicine, and colleagues used data from over 6,000 person-observations from the Framingham Heart Study to determine the effect of soft drink consumption on the development of metabolic syndrome. This syndrome is characterized by increases in waist circumference, blood pressure, serum triglyercides and blood glucose as well as aberrations in cholesterol levels.
Individuals who drank one or more soft drinks per day had a 48 percent increased risk of having metabolic syndrome compared to those who drank less than one soda per day. Rates of new-onset metabolic syndrome were also higher in patients who drank one or more sodas per day. Using parallel data obtained through a questionnaire, prevalence and incidence of metabolic syndrome is largely identical regardless of whether drinking diet or regular soda.
"The present observational data raise the possibility that public health policy measures to limit the rising consumption of soft drinks in the community may be associated with a lowering of the burden of metabolic risk factors in adults," the authors write.
Prophylactic Anticoagulation Reduces Clots, Not Deaths
Meta-analysis shows that hospital patients benefit from reduced venous thromboembolic risks
Routine prophylactic anticoagulation in hospitalized patients can reduce venous thromboembolic risks compared to placebo, but not mortality, according to study findings published in the July 23 issue of the Archives of Internal Medicine.
Henry Krum, Ph.D., of Monash University and Alfred Hospital in Melbourne, Australia, and colleagues conducted a meta-analysis of 36 randomized controlled trials. Fourteen trials compared unfractionated heparin with a control, 11 compared low-molecular-weight heparin to a control, 10 compared the two types of heparin to each other, and one compared fondaparinux sodium with placebo.
Compared to placebo, the researchers found that both unfractionated heparin and low-molecular-weight heparin were associated with lower risks of deep vein thrombosis (67 percent and 44 percent, respectively) and pulmonary embolism (36 percent and 63 percent, respectively). They also found that low-molecular-weight heparin was associated with lower risks compared to unfractionated heparin for deep vein thrombosis (32 percent) and hematoma (53 percent). Neither therapy, however, was associated with lower death rates compared to placebo.
"We believe that routine prophylactic anticoagulation has an important place in the medical setting," the authors conclude. "Although such therapy may not necessarily decrease mortality among hospitalized medical patients, it will reduce the occurrence of deep vein thrombosis and pulmonary embolism and therefore the burden of illness currently caused by these events."
Health Literacy Affects Survival in Elderly
Those with inadequate literacy have higher risk of all-cause mortality and cardiovascular death
In older patients, an inability to read and understand basic health information independently predicts an increased five-year risk of all-cause mortality and cardiovascular death, according to research published in the July 23 issue of the Archives of Internal Medicine.
David W. Baker, M.D., of Northwestern University Feinberg School of Medicine in Chicago, and colleagues interviewed 3,260 Medicare patients in 1997 and determined that 2,094 (64.2 percent) had adequate health literacy, 366 (11.2 percent) had marginal health literacy and 800 (24.5 percent) had inadequate health literacy. They used the National Death Index to identify subjects who died through 2003.
The researchers found that the crude mortality rates were significantly higher for subjects with inadequate or marginal health literacy (39.4 and 28.7 percent, respectively) compared to those with adequate literacy (18.9 percent). After adjusting for other factors, the investigators found that the rates for all-cause mortality and cardiovascular death were still considerably higher in those with inadequate or marginal literacy.
"Widespread improvements in health and health care communication will likely be necessary to reduce the association between health literacy and mortality," the authors conclude. "To achieve this goal, we must further elucidate the causal pathways linking health literacy and adverse health outcomes and use this information to design more comprehensive and effective interventions."
Benefits of Drug-Eluting Stents May Outweigh Risks
Reduced target lesion revascularization seen as more important than slightly increased risk of myocardial infarction
The benefit of drug-eluting stents, a reduction in the risk of clinically necessary target lesion revascularization, appears to outweigh the slightly increased risk of later stent thrombosis and myocardial infarction, according to a report published in the July 31 issue of the Journal of the American College of Cardiology.
Lisette Okkels Jensen, M.D., Ph.D., of Odense University Hospital in Odense, Denmark, and colleagues analyzed 2002-2005 data from the Western Denmark Heart Registry on 12,395 patients, including 3,548 who received drug-eluting stents and 8,847 who received bare metal stents.
During the 12 to 15 months after implantation, the researchers found that patients who received drug-eluting stents were more likely than those who received bare metal stents to experience late definite stent thrombosis (hazard ratio, 10.93) or myocardial infarction (HR, 4.0).
"The overall rates of stent thrombosis, myocardial infarction, and death were similar among the patients treated with the two stent types," the authors write. "Furthermore, use of drug-eluting stents reduced the risk of clinically necessary target lesion revascularization by 43 percent. The minor risk of stent thrombosis and myocardial infarction within 15 months after implantation of drug-eluting stents seems unlikely to outweigh the benefit of these stents."
Thyroid Function Linked to Death Risk in Cardiac Patients
Even mild forms of dysfunction may increase risk of cardiac and other forms of death
In patients with heart disease, even mild thyroid dysfunction may be associated with an increased risk of death, according to the results of a study published in the July 23 issue of the Archives of Internal Medicine.
Giorgio Iervasi, M.D., of the Clinical Physiology Institute in Pisa, Italy, and colleagues studied 3,121 cardiac patients who were divided into four groups: euthyroidism, subclinical hypothyroidism, subclinical hyperthyroidism, and low triiodothyronine syndrome.
After adjusting for other risk factors, the researchers found that the risk of cardiac death was higher in the subclinical hypothyroidism group, subclinical hyperthyroidism group and low triiodothyronine group (hazard ratios, 2.40, 2.32 and 1.63, respectively) than in euthyroidism. They also found that the risk of overall death was higher in subclinical hypothyroidism and low triiodothyronine syndrome (HR, 2.01 and 1.57, respectively).
"The observed negative prognostic impact of any form of mild thyroid dysfunction in cardiac patients reinforces the hypothesis that a normal thyroid status is essential for maintaining systemic and cardiovascular homeostasis; when a normal thyroid status is persistently lost, increased whole-body and cardiovascular vulnerability is observed," the authors conclude.
Cardioverter Defibrillators Showing Greater Benefit
In hypertrophic cardiomyopathy patients with just one risk factor, the implantable devices help prevent sudden cardiac death
In patients with hypertrophic cardiomyopathy, the risk of sudden cardiac death is lower in those who have an implantable cardioverter-defibrillator (ICD), according to a study published in the July 25 issue of the Journal of the American Medical Association.
Barry J. Maron, M.D., of the Minneapolis Heart Institute Foundation, and colleagues analyzed data on 506 patients with hypertrophic cardiomyopathy -- including 51 with only a single risk factor for sudden death -- who received an ICD between 1986 and 2003.
The researchers found that the ICDs appropriately terminated ventricular tachycardia/fibrillation in 103 (20 percent) of the patients. They also found that appropriate ICD discharge rates were similar for patients with one, two, and three or more risk factors (3.83, 2.65, and 4.82 per 100 person-years, respectively).
"Patients with two or more risk factors likely present a high enough risk to warrant implantation of an ICD," state the authors of an accompanying editorial. "However, the decision to implant an ICD in any patient, especially one with a single risk factor, must include a thorough and earnest discussion of the accuracy of the current risk assessment tools, the risks and benefits of ICD therapy, and the individual patient's viewpoints on procedures, devices, and death. Such an approach will allow the patient-physician team to arrive at an individualized decision regarding ICD implantation."
Some of the authors report serving as consultants and receiving speakers' fees and honoraria from ICD manufacturing companies.
Hip Protector Ineffective for Nursing Home Residents
No significant difference seen in fracture rates for protected versus unprotected hips
Among elderly nursing home residents, the use of a hip protector does not reduce the incidence of fracture, according to study findings published in the July 25 issue of the Journal of the American Medical Association.
Douglas P. Kiel, M.D., of Hebrew SeniorLife and Harvard Medical School in Boston, and colleagues studied 1,042 residents (average age 85) of 37 nursing homes who wore a hip protector on one hip only so they could serve as their own controls. Overall participant adherence was 73.8 percent and mean participation duration was 7.8 months.
After 20 months of follow-up, the researchers terminated the study because there was no significant difference in fracture rates between protected and unprotected hips (3.1 percent versus 2.5 percent). In a subanalysis of 334 residents with greater than 80 percent adherence, they also found no significant difference in fracture rates between protected and unprotected hips (5.3 percent versus 3.5 percent).
"Although Kiel et al. provide useful data from an important trial, these findings and those from past studies are not sufficient to make evidence-based recommendations for or against use of hip protectors among frail, nursing home residents," state the authors of an accompanying editorial, who argue that more randomized studies are needed to settle the issue.
Meta-Analyses Often Contain Data-Extraction Errors
Researchers find errors in up to 63 percent of studies based on standardized mean differences
A high percentage of meta-analyses based on standardized mean differences may contain data-extraction errors that negate or even reverse their findings, researchers report in the July 25 issue of the Journal of the American Medical Association.
Peter C. Gotzsche, M.D., of the Nordic Cochrane Centre in Copenhagen, Denmark, and colleagues conducted a systematic review of 27 meta-analyses published in 2004 that reported a result as a standardized mean difference. They randomly selected two trials from each meta-analysis and tried to duplicate the results by independently calculating the standardized mean difference using Hedges adjusted g. Their primary outcome was the proportion of meta-analyses that differed from that of the authors by 0.1 or more in at least one of the two selected trials.
The researchers found that 10 (37 percent) of the meta-analyses did not meet the primary outcome. After performing their own meta-analysis, Gotzsche's team found that the results in seven of these 10 meta-analyses were erroneous. They also found that 17 (63 percent) of the meta-analyses contained an error in at least one of the two trials.
"This has implications for researchers and implies that all readers, including journal reviewers and policy makers, should approach such meta-analyses with caution," the authors conclude.
Pulmonary Artery Catheterizations Fall Sharply
Since 1993, the rate at which hospitals perform the procedure has decreased by 65 percent
Since 1993, pulmonary artery catheterization has dramatically declined in hospitals within the United States in response to a growing body of evidence that the procedure does not benefit and may even harm patients, according to a report published in the July 25 issue of the Journal of the American Medical Association.
Renda Soylemez Wiener, M.D., and H. Gilbert Welch, M.D., of the Department of Veterans Affairs Medical Center in White River Junction, Vt., assessed data from the Nationwide Inpatient Sample.
Between 1993 and 2004, the researchers found that pulmonary artery catheterizations decreased from 5.66 to 1.99 per 1,000 medical admissions, representing a decline of 65 percent. Among diagnoses often associated with pulmonary artery catheterization, they observed the most precipitous declines in myocardial infarction (81 percent) and septicemia (54 percent).
"The 40-year story of the pulmonary artery catheter is nearing its end," state the authors of an accompanying editorial. "It is a cautionary tale of rapid adoption and slow evaluation of a monitoring device that, when used correctly, provides exquisitely detailed physiological data that, regrettably, does not appear to benefit patients. Older clinicians will look back wistfully on the hours spent placing, troubleshooting, and debating the data from the pulmonary artery catheter. Younger colleagues will just wonder what all the fuss was about."
Link Seen Between Low Cholesterol and Cancer
Statin users who achieve low LDL levels have slightly higher risk of newly diagnosed cancer
Cardiac patients who achieve low LDL levels with statin therapy may have a slightly increased risk of cancer, but the cardiovascular benefits of statin therapy still outweigh the risks, according to study findings published in the July 31 issue of the Journal of the American College of Cardiology.
Richard H. Karas, M.D., of the Tufts University School of Medicine in Boston, and colleagues analyzed 23 statin treatment arms that included 75,317 patients to assess the link between low-density lipoprotein (LDL) lowering and liver or muscle damage, and 13 treatment arms that included 41,173 patients to assess the link between LDL lowering and cancer.
The researchers found no link between LDL lowering and liver or muscle damage, but found a significant association between high statin doses and elevated liver enzymes. In patients with lower achieved LDL levels, they found a higher rate of newly diagnosed cancer, about one extra incident per 1,000 patients.
"These current findings provide insufficient evidence that there is any problem with LDL lowering that outweighs its significant benefits on vascular disease," states the author of one of two accompanying editorials. However, "we must continue to be vigilant in ensuring that its benefit clearly outweighs its risk."
Steroid Similar to Placebo for Bronchiolitis in Infants
Drug does not improve rates of hospital admission, respiratory status or later outcomes
Dexamethasone does not improve rates of hospital admission, respiratory status or later outcomes such as adverse events in infants with moderate-to-severe bronchiolitis compared with placebo, according to the results of a study published in the July 26 issue of the New England Journal of Medicine.
Howard M. Corneli, M.D., from the University of Utah in Salt Lake City, and colleagues randomized 600 infants (two to 12 months old) with moderate-to-severe bronchiolitis diagnosed in the emergency department to placebo or a single dose of dexamethasone (1 mg/kg).
The researchers found the rate of hospital admission within four hours of the emergency department visit was similar in the placebo and dexamethasone groups (41 percent versus 39.7 percent, respectively). Respiratory status improved to a similar extent in both groups, as assessed by the four-hour Respiratory Assessment Change Score. Later outcomes such as length of hospital stay, adverse events and later medical visits or admissions were also similar in both groups.
"Despite the value of this study, the long history of therapies and recommendations attending bronchiolitis suggest that the study's results will not appreciably change the nature of the care provided by the primary physician faced with a young, distressed infant and anxious parents," Caroline B. Hall, M.D., from the University of Rochester School of Medicine and Dentistry in Rochester, N.Y., writes in an accompanying editorial.
Vioxx Increases Cardiovascular Events in Cancer Patients
Risk increased within two weeks of treatment
Vioxx (rofecoxib), a cyclooxygenase-2 inhibitor, increases the risk of adverse cardiovascular events within two weeks of treatment, according to a report in the July 26 issue of the New England Journal of Medicine. The study authors note that the trial was ended early due to withdrawal of Vioxx from the worldwide market.
David J. Kerr, M.D., from the University of Oxford in the United Kingdom, and colleagues examined the frequency of adverse cardiovascular events in 2,434 patients with stage II or III colorectal cancer who had been randomized to either placebo or 25 milligrams of rofecoxib daily.
The researchers found that after a median treatment of 7.4 months, there were 23 confirmed cardiovascular thrombotic events. Of these, 16 occurred in the rofecoxib group within 14 days of treatment (estimated relative risk 2.66). Four rofecoxib patients and two placebo patients died from thrombotic causes within 14 days of treatment. There were 14 additional cardiovascular thrombotic events, six of which were in the rofecoxib group, in the two years after trial closure (unadjusted relative risk 1.50), though this was not statistically significant.
"Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months' duration," Kerr and colleagues conclude.
The authors of this study report receiving consulting fees and honoraria from Merck and other pharmaceutical companies.
Aortic Dissection Mortality Higher with Lumen Thrombosis
Increased risk seen from acute aortic dissection after hospital discharge
Partial thrombosis of the false lumen after acute aortic dissection is associated with an increased risk of death after hospital discharge, according to a report in the July 26 issue of the New England Journal of Medicine.
Thomas T. Tsai, M.D., from the University of Michigan Cardiovascular Center in Ann Arbor, and colleagues examined outcomes in 201 patients with type B acute aortic dissection after hospital discharge based on patency or thrombosis of the false lumen.
The researchers found that 56.7 percent of patients had a patent false lumen, 33.8 percent had a partial thrombosis of the false lumen, and 9.5 percent had complete thrombosis of the false lumen. The mean three-year post-discharge mortality rate ranged from 13.7 to 31.6 percent for these conditions and was highest for partial thrombosis. Post-discharge mortality was independently predicted by partial thrombosis of the false lumen (relative risk 2.69), a history of aortic aneurysm (RR, 2.05), and a history of atherosclerosis (RR, 1.87).
"Mortality is high after discharge from the hospital among patients with type B acute aortic dissection," Tsai and colleagues conclude. "Partial thrombosis of the false lumen, as compared with complete patency, is a significant independent predictor of post-discharge mortality in these patients."
The authors report receiving consulting and lecture fees from medical device and pharmaceutical companies.
Obese Friends, Family Boosts Personal Obesity Risk
Obese 'network' can extend to three degrees of separation
People who have obese siblings, friends or spouses are more likely to become obese themselves, researchers report in the July 26 issue of the New England Journal of Medicine.
Nicholas A. Christakis, M.D., Ph.D., from Harvard Medical School in Boston, and James H. Fowler, Ph.D., from the University of California San Diego, examined whether weight gain in one person was associated with weight gain in their siblings, spouses, neighbors and friends in 12,067 socially connected individuals from 1971 to 2003.
The researchers found clusters of obese persons (body mass index of 30 or more) that extended to three degrees of separation. Having an obese friend increased the risk of becoming obese by 57 percent, having an obese sibling increased the risk by 40 percent, and having an obese spouse increased the risk by 37 percent. The influence was greater among people of the same gender.
"Networks, in this case those that pertain to social influence, may have just as strong an impact on the development of obesity as the otherwise strong genetic effects," Albert-Laszlo Barabasi, Ph.D., from the University of Notre Dame in Indiana, writes in an accompanying editorial.
Prepared jointly by the editors of Medical Economics and HealthDay's Physicians' Briefing (www.physicianbriefing.com)