Latest Research

September 7, 2007

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

Some Aortic Dissections May Need Earlier Intervention

Initial false lumen diameters equal to or greater than 22 mm may predict adverse outcomes

Acute distal aortic dissection patients with large false lumen diameters may be at higher risk for aneurysm or death and as such make better candidates for early intervention than other such patients, according to a report in the Aug. 21 issue of the Journal of the American College of Cardiology.

Jong-Min Song, M.D., Ph.D., of the University of Ulsan College of Medicine in Seoul, South Korea, and colleagues sought to identify early predictors for aneurysm or death among 100 patients with aortic dissection.

Patients who had a large (22 mm or more diameter) initial false lumen at the upper descending thoracic aorta were most likely to show accelerated aorta dilation, develop aortic aneurysms and/or die. This finding had a sensitivity of 100 percent and a specificity of 76 percent. As such, these are the patients who could benefit from early surgical or percutaneous interventions including stent grafting.

A forthcoming trial should add a subgroup analysis comparing the outcomes of false lumen diameter of less than 21 mm to those equal to or greater than 22 mm, suggested Eric M. Isselbacher, M.D., of Massachusetts General Hospital in Boston, in an accompanying editorial. "Doing so would maximize the likelihood that this pivotal trial will succeed in identifying, at the very least, a subgroup of acute distal aortic dissection patients that significantly benefit from prophylactic aortic stent-grafting."

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In COPD, Men More Likely to Have Severe Emphysema

At all stages of severity, men have significantly more computed tomography emphysema

Among patients with chronic obstructive pulmonary disease (COPD), men are more likely than women to have more extensive computed tomography emphysema at all stages of severity, according to research published in the August issue of Chest.

Mark T. Dransfield, M.D., of the University of Alabama at Birmingham, and colleagues studied 396 patients, including 246 men and 150 women. All were current and former smokers enrolled in the National Lung Screening Trial.

The researchers found that men had more regional and total computed tomography emphysema than women at stage 0 (3.9 percent versus 2.4 percent), stage I (7 percent versus 3.7 percent), stage II (7.8 percent versus 5.5 percent), and stages III/IV (15.8 percent versus 8.7 percent). Their multivariate regression analysis found that only gender and the forced expiratory volume in one second/forced vital capacity ratio predicted the total percentage of low attenuation areas.

"These data argue that computed tomography emphysema develops more quickly in men than in women and that smoking alone does not explain the discrepancy," the authors conclude. "It is possible that this gender difference in radiologic expression of COPD may in part explain the differences between men and women in the natural history of the disease. Gender differences in the pathophysiology and treatment of COPD warrant additional study."

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Implantable Defibrillators May Reduce Mortality

However, device failure rates may be underestimated in randomized controlled trials, observational studies

In adult patients with left ventricular systolic dysfunction, implantable cardioverter defibrillators, or ICDs, effectively reduce the risk of death, according to a systematic review published in the Aug. 21 issue of the Annals of Internal Medicine.

Finlay A. McAlister, M.D., of the University of Alberta Hospital in Edmonton, Alberta, Canada, and colleagues performed a meta-analysis of 12 randomized controlled trials involving 8,516 patients that assessed mortality and 76 observational studies involving 96,951 patients that assessed safety or effectiveness.

The researchers found that ICDs reduced all-cause mortality in the randomized controlled trials and observational studies by 20 percent and 46 percent, respectively. They also found that the most common post-implantation complications per 100 patient-years were lead problems (1.5), device malfunctions (1.4) and site infections (0.6). Inappropriate discharges per 100 patient-years ranged from 19.1 in the randomized controlled trials to 4.9 in the observational studies.

"While we report on patient and device-related complication rates in this review, it should be recognized that it is difficult to estimate the true incidence of ICD device failure. The observed failure rates are probably underestimated because of the tendency to attribute patient deaths to the underlying disease process rather than unrecognized device malfunction," the authors write. "Improved risk stratification to identify patients who are most likely to benefit from ICD are needed."

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Remote Navigation, Ablation Corrects Atrial Fibrillation

Particularly effective in cases of pulmonary vein antrum isolation

Remote magnetic navigation and ablation of the pulmonary veins can treat drug-refractory atrial fibrillation, and is more likely to succeed with complete pulmonary vein antrum isolation, according to study findings published in the Aug. 28 issue of the Journal of the American College of Cardiology.

Andrea Natale, M.D., and colleagues from The Cleveland Clinic in Ohio tested the effectiveness of remote magnetic navigation and ablation of atrial fibrillation in 45 patients. A stepwise approach was used: circumferential pulmonary vein ablation, pulmonary vein antrum isolation (PVAI), and PVAI using the conventional approach if unsuccessful. They used a Niobe II remote magnetic system made by Stereotaxis in St. Louis.

The researchers found that remote navigation using the wand rather than the coordinate approach was successful in reaching the target location in all cases. Charring on the ablation catheter tip, which could cause an embolism, was observed in 33 percent of cases. After a mean follow-up of 11 months, 22 percent of patients with complete PVAI and 90 percent of patients with incomplete PVAI had a recurrence.

"The study…demonstrates that when PVAI is the standard, complete isolation of the pulmonary vein antrum portends a modest risk of atrial fibrillation but that recurrence rates are very high when this end point is not achieved," Bruce D. Lindsay, M.D., from Washington University School of Medicine in St. Louis, writes in an accompanying editorial.

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On-Demand Surgery for Peritonitis Less Costly

Similar morbidity, mortality as planned relaparotomy but less costly

In patients with severe secondary peritonitis, on-demand relaparotomy has similar rates of morbidity and mortality as planned relaparotomy but with shorter hospital stays and lower medical costs, according to a report in the Aug. 22/29 issue of the Journal of the American Medical Association.

Marja A. Boermeester, M.D., Ph.D., from the Academic Medical Center in Amsterdam, the Netherlands, and colleagues randomized 232 patients with severe secondary peritonitis to on-demand or planned relaparotomy.

The researchers found that 12-month morbidity and mortality were similar in the on-demand and planned groups (57 versus 65 percent). Forty-two percent of the on-demand group and 94 percent of the planned group had a relaparotomy. The on-demand group had significantly shorter median stays in the intensive care unit, shorter median hospital stays, and 23 percent lower direct medical costs per patient.

"The results are consistent with the notion that an on-demand relaparotomy approach may improve outcomes and save health care resources," David R. Flum, M.D., and Farhood Farjah, M.D., from the University of Washington in Seattle, write in an accompanying editorial.

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Hypertension Frequently Undiagnosed in Children

Age, frequency of abnormal blood pressure readings increase odds of diagnosis

Hypertension and prehypertension are frequently undiagnosed in children and adolescents, with factors such as age and frequency of abnormal blood pressure readings increasing the likelihood of diagnosis, researchers report in the Aug. 22/29 issue of the Journal of the American Medical Association.

David C. Kaelber, M.D., Ph.D., from Harvard Medical School in Boston, and colleagues assessed the frequency of prehypertension or hypertension in 14,187 children and adolescents aged 3 to 18 years, who were seen at least three times for well-child care.

The researchers found that 3.6 percent of children or adolescents had hypertension, of whom 26 percent had documented high blood pressure, and 3.4 percent of children had prehypertension, which was documented in 11 percent of cases. Older age and frequency of elevated blood pressure readings increased the likelihood of being diagnosed with prehypertension, while greater height-for-age percentile and having an obesity-related diagnosis increased the likelihood of being diagnosed with hypertension.

"Hypertension and prehypertension were frequently undiagnosed in this pediatric population," Kaelber and colleagues conclude. "Patient age, height, obesity-related diagnoses, and magnitude and frequency of abnormal blood pressure readings all increased the odds of diagnosis."

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Genetic Studies Claiming Gender Differences Often Flawed

Many insufficiently documented or spurious

Studies that claim that the genetic effects for common diseases or traits vary depending on gender are often insufficiently documented or spurious, researchers report in the Aug. 22/29 issue of the Journal of the American Medical Association.

John P.A. Ioannidis, M.D., from the University of Ioannina in Greece, and colleagues reviewed 77 published genetic-association studies containing 432 claims of sex differences for genetic effects.

The researchers found that 66.2 percent of studies claimed that sex comparisons were decided a priori. Only 12.7 percent of claims had appropriate documentation of gene-sex interaction, while the remainder of claims were insufficient or spurious. Of 188 claims with data for reanalysis, 44.1 percent were nominally statistically significant (p=0.05 threshold), and 53 percent of these had modest p values of 0.01 to 0.05. Only one of 60 claims that appeared to have good internal validity was consistently replicated in at least two other studies.

"In this sample of highly prominent claims of sex-related differences in genetic associations, most claims were insufficiently documented or spurious, and claims with documented good internal and external validity were uncommon," the authors conclude.

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Ultrasound Device Stimulates Heart Without Pacing Lead

Device safe and effective in short term

A new ultrasound device that achieves cardiac stimulation without a pacing lead is safe and effective in patients in the short term, researchers report in a study published in the Aug. 28 issue of the Journal of the American College of Cardiology.

Kathy L. Lee, M.B.B.S., from the University of Hong Kong in China, and colleagues examined whether a device inserted transvenously into the heart that converts ultrasound energy to electrical energy could achieve cardiac stimulation without the use of a pacing lead. The device was tested in 80 pacing sites in 24 patients during or after electrophysiology procedures.

The researchers found that pacing was successful at all sites, with consistent capture at 77 sites. The mean transmit-to-receive distance was 11.3 centimeters, the mean mechanical index during pacing was 0.5, and the mean ultrasound-mediated capture threshold was 1.01 volts. There were no adverse events or reports of patient discomfort.

"The feasibility and safety of cardiac stimulation using a remote energy source, without pain or discomfort, has been shown in the short term in patients for the first time," Lee and colleagues conclude.

The study was supported by a grant from EBR Systems Inc.

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Bariatric Surgery Increases Longevity for Obese

Studies show that surgical patients lose more weight and live longer than non-surgical patients

In severely obese patients, bariatric surgery leads to sustained weight loss and reduces the risk of death, according to two studies published in the Aug. 23 issue of the New England Journal of Medicine.

Lena M.S. Carlsson, M.D., Ph.D., of Gothenburg University in Sweden, and colleagues compared outcomes in 2,010 patients who underwent bariatric surgery and 2,037 control patients who received conventional treatment. The investigators found that the surgical patients lost 14 percent to 25 percent of their body weight after 10 years while the control group's change in body weight was less than plus or minus 2 percent. The surgical group also had a lower adjusted risk of death (hazard ratio, 0.71), the report indicates.

Ted D. Adams, Ph.D., of the University of Utah School of Medicine in Salt Lake City, and colleagues compared outcomes in 9,949 patients who underwent bariatric surgery and 9,628 controls. After a mean follow-up of 7.1 years, the researchers found that the adjusted long-term mortality from any cause was 40 percent lower in the surgical group.

These studies "show that weight loss saves lives in obese patients," states the author of an accompanying editorial. "Thus, the question as to whether intentional weight loss improves life span has been answered, and the answer appears to be a resounding yes."

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Sexual Activity Often Continues into Older Age

One-quarter of people aged 75 to 85 are still sexually active

Many older adults in the United States continue to have sex into their 70s and 80s, although they do have a high prevalence of sexual problems compared to younger patients, researchers report in the Aug. 23 issue of the New England Journal of Medicine.

Stacy Tessler Lindau, M.D., of the University of Chicago, and colleagues surveyed 3,005 U.S. adults, including 1,550 women and 1,455 men, aged 57 to 85.

The researchers found that the prevalence of sexual activity was 73 percent in subjects aged 57 to 64 years, 53 percent in those aged 65 to 74, and 26 percent in those aged 75 to 85. Among those who were sexually active, the most common sexual problem for women was low desire (43 percent) and the most common problem for men was erectile dysfunction (37 percent). Only 22 percent of women and 38 percent of men reported discussing sexual problems with a physician after age 50.

"For some older couples, sex can continue to play an important part in their relationship and well-being, and some may benefit from counseling or medication for that purpose," states the author of an accompanying editorial. "The medical profession should encourage older patients to feel comfortable in discussing sexual problems and in choosing whichever of these two options suits them best."

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Soldiers' Eardrum Perforation Linked to Brain Injury

Study of blast-injury survivors shows association between perforation and unconsciousness

Eardrum perforation is a significant marker of concussive brain injury in U.S. soldiers who are exposed to explosive devices in Iraq, according to a letter published in the Aug. 23 issue of the New England Journal of Medicine.

Michael S. Xydakis, M.D., Lt. Col., of the Air Force Theater Hospital, Balad Air Base in Iraq, and colleagues evaluated 210 male blast-injury survivors who were evaluated for tympanic-membrane perforation and loss of consciousness.

Xydakis and colleagues found that the overall incidences of tympanic-membrane perforation and loss of consciousness were 35.2 percent and 35.7 percent, respectively, and that the two factors were strongly associated (relative risk, 2.76).

"Our observation that there was a significant association between barotraumatic tympanic-membrane perforation and concussive brain injury suggests that physicians who are treating blast survivors with tympanic-membrane perforation need to have a high index of suspicion for concomitant neurologic injury," the authors conclude.

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Metabolic Syndrome Increases Death After Bypass Surgery

Risk also higher in those with metabolic syndrome plus diabetes

Patients with metabolic syndrome alone or with diabetes have a higher risk of death after coronary artery bypass grafting surgery than those who do not, according to the results of a study published in the Aug. 28 issue of the Journal of the American College of Cardiology.

Patrick Mathieu, M.D., from the Hopital Laval in Quebec, Canada, and colleagues retrospectively examined mortality in 5,304 patients who had undergone coronary artery bypass grafting surgery, of which 46 percent had metabolic syndrome.

The researchers found that after adjusting for other risk factors, the risk of operative mortality was significantly higher in those with metabolic syndrome (relative risk, 2.36) and metabolic syndrome plus diabetes (relative risk, 2.69). The risk was not significantly higher in patients with diabetes alone. About 2.4 percent of patients with metabolic syndrome died after surgery, compared with 0.9 percent of those without metabolic syndrome.

"This is the first study to report that metabolic syndrome is a highly prevalent and powerful risk factor for operative mortality in patients undergoing a coronary artery bypass grafting surgery," Mathieu and colleagues conclude.

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Recent Myocardial Infarction Linked to Diabetes Risk

One-third of such patients develop impaired fasting glucose or diabetes

In patients with recent myocardial infarction, one-third develop impaired fasting glucose or diabetes within 3.5 years, researchers report in the August issue of The Lancet. Lifestyle factors of smoking and higher body mass index appear to be independent risk factors for developing diabetes, whereas a Mediterranean-type diet appears to confer protection.

Dariush Mozaffarian, M.D., of Harvard Medical School in Boston, and colleagues analyzed data from 8,291 Italian patients with myocardial infarction within the previous three months who did not have diabetes at baseline.

Of 7,533 patients without impaired fasting glucose at baseline, one-third developed new impaired fasting glucose or diabetes during a mean follow-up of 3.2 years. Risk factors included older age, hypertension, beta-blocker use, diuretic use, higher body mass index, current smoking and lower Mediterranean diet score. The annual risk of developing diabetes was increased in patients with recent myocardial infarction compared to the general population (1.8 percent versus 27.5 percent).

"The high risk of incident impaired fasting glucose and diabetes in patients who had a myocardial infarction has clinical implications, indicating the importance of both surveillance and prevention of prediabetes and diabetes in these individuals," the authors conclude.

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Calcium, Vitamin D Reduce Fracture Risk in People Over 50

Supplements also reduce rate of bone loss

Calcium supplementation alone or with vitamin D reduces the risk of fracture and the rate of bone loss in middle-aged and elderly individuals, according to a review of published studies in the Aug. 25 issue of The Lancet.

Benjamin M.P. Tang, M.D., from the University of Sydney in Australia, and colleagues performed a meta-analysis of 29 randomized trials involving 63,897 patients aged 50 years or older. They looked at whether calcium alone or with vitamin D could prevent fracture and osteoporotic bone loss.

The researchers found a 12 percent lower risk of fracture (24 percent where compliance was high) in the 17 trials examining fracture. In the 23 trials that examined bone mineral density, the rate of bone loss was reduced by 0.54 percent in the hip and by 1.19 percent in the spine. Better results were obtained with calcium doses of at least 1200 mg and vitamin D doses of at least 800 IU.

"Evidence supports the use of calcium, or calcium in combination with vitamin D supplementation, in the preventive treatment of osteoporosis in people aged 50 years or older," the authors conclude. "For best therapeutic effect, we recommend minimum doses of 1200 mg of calcium, and 800 IU of vitamin D (for combined calcium plus vitamin D supplementation)."

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Most Cardiac Arrests in Schools Occur in Adults

School-based CPR and automated external defibrillators may benefit staff and visitors more than students

About 90 percent of cases of cardiac arrest in schools occur in adults -- such as faculty, staff and other adults including visitors -- not students, according to study findings published online Aug. 27 in Circulation: Journal of the American Heart Association.

Lindsay White, M.P.H., from Public Health Seattle and King County in Seattle, and colleagues examined the characteristics of cardiac arrests at schools in Seattle and King County treated by emergency medical services from 1990 to 2005.

The researchers found that there were 97 cases of cardiac arrest at schools during this period, accounting for 2.6 percent of public location cardiac arrests, of which 12 occurred in students, 33 occurred in faculty and staff, and 45 occurred in other adults. Many of these were witnessed and received bystander cardiopulmonary resuscitation (CPR). The annual incidence of cardiac arrest was about 25 times higher in faculty and staff than students (4.51 versus 0.18 per 100,000 person-years).

The study "supports the assertion that school-based CPR and automated external defibrillator programs would benefit faculty and staff members, as well as visitors to the school who, because of their age, are at greater risk of cardiac arrest than the students," White and colleagues conclude.

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Risky Coronary Artery Lesions Counted, Located

Thin-capped fibroatheroma and ruptured plaques common, but not plentiful

Lesions believed to precipitate heart attacks can be found in many hearts, but within individual hearts they are limited in number and concentrated in specific areas of the coronary arteries, according to study findings published in the Sept. 4 issue of the Journal of the American College of Cardiology.

Aloke V. Finn, M.D., of Massachusetts General Hospital in Boston, and colleagues dissected 50 hearts: 33 from those who died of cardiovascular causes, 13 from those who died from non-cardiovascular causes and four from those who died of unknown causes (64 percent male; mean age 73 years). Longitudinal arterial sections were analyzed to identify advanced coronary lesions.

At least one thin-capped fibroatheroma or ruptured plaque was found in 20 of the hearts examined (40 percent), but an average of only 2.1 lesions of either type was found in each of those 20 hearts. Most thin-capped fibroatheroma or ruptured plaques were clustered in the proximal left anterior descending and left circumflex arteries. In a variety of advanced lesions, an inverse relationship was observed between necrotic core size and cap thickness.

"Assessing several characteristics of a given plaque could potentially enhance invasive risk stratification by identifying very high-risk plaques," note the authors of an accompanying editorial, "thereby lowering the number of vulnerable plaques that deserve to be followed over time and ultimately treated."

Several of the study authors are employed by or own stock in InfraReDx Inc., which funded the study.

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Coronary Calcium Riskier for Blacks Than Other Groups

High readings predict earlier mortality for many ethnicities

High levels of coronary artery calcium are significant predictors of early mortality across a broad range of ethnic groups, but some ethnicities are more profoundly affected than others, according to a population study published in the Sept. 4 issue of the Journal of the American College of Cardiology.

Khurram Nasir, M.D., of the Harvard School of Medicine in Boston, and colleagues followed 14,812 asymptomatic individuals who were referred by their primary care physicians for coronary artery calcium screening between 1991 and 2004 because of risk factors. The study sample included 637 blacks, 1,065 Asians, 1,334 Hispanics and 11,776 non-Hispanic whites. The study's primary end point was death from all causes (505 individuals) after a follow-up period of 10 years.

Coronary artery calcium was found to be the single greatest predictor of time to mortality for all the ethnicities. Death rates were low or very low across all ethnic groups for individuals with coronary artery calcium scores in the low range (up to 10). When coronary artery calcium scores were in the very high range (1,000 or higher) survival rates were 80 percent for Asians, 60 percent for Hispanics, 57 percent for non-Hispanic whites and 30 percent in blacks.

"As with all translational research, the current study is but one more step in understanding the nature of coronary atherosclerosis and its individual consequences," states the author of an accompanying editorial.

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Family, Friends Learn CPR When Young Teens Given Kits

But training has no effect on incidence of bystander CPR in short term

Distributing kits and instructional materials for cardiopulmonary resuscitation (CPR) to young adolescents increases CPR training among their family and friends, too, though it has no effect on the incidence of bystander CPR in the short term, according to a report published online Aug. 27 in Circulation: Journal of the American Heart Association.

Dan L. Isbye, M.D., from Copenhagen University Hospital in Denmark, and colleagues evaluated questionnaires from 6,947 schoolchildren (aged 12 to 14 years) who had been given CPR resuscitation manikins and an instructional DVD. They determined if students had used the kit to learn CPR.

The researchers found that the kits had been used to train 17,140 family and friends (mean, 2.5 persons per student). The students' teachers spent a mean of 64 minutes to prepare and a mean of 13 minutes to clean up. The incidence of bystander CPR in the months after training did not significantly increase compared with the previous year, the authors note.

"CPR training can be disseminated in a population by distributing personal resuscitation manikins among children in primary schools," Isbye and colleagues conclude.

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Labor Induction May Lower Caesarean Delivery Rates

Half as many women offered induced labor have Caesareans compared to those not given the option

Greater use of prostaglandin-induced labor may cut Caesarean delivery rates by half, researchers report in the July/August issue of the Annals of Family Medicine.

James Nicholson, M.D., of the University of Pennsylvania Health System in Philadelphia, and colleagues compared birth outcomes and Caesarean delivery rates over four years in 794 women offered prostaglandin-induced labor with 1,075 non-exposed women not given the alternative.

The researchers found that 31.4 percent of women given the induced labor option had induced labor, 23.3 percent used prostaglandin, and 5.3 percent had Caesarean deliveries, versus 20.4 percent, 15.7 percent and 11.8 percent of non-exposed women, respectively.

"A preventive approach to reducing Caesarean deliveries may be possible," the authors write. "This study found that practitioners who often used risk-guided, prostaglandin-assisted labor induction had a lower Caesarean delivery rate without increases in rates of other adverse birth outcomes."

In an accompanying editorial, Aaron Caughey, M.D., Ph.D., of the University of California San Francisco, notes that if studies back these findings, "scheduled induction of labor may provide a tool for clinicians delivering babies to decrease both the maternal and neonatal complications in term pregnancies."

The authors of this study report receiving financial support and supplies from Forest Pharmaceuticals.

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Newer Device Provides Support Until Heart Transplant

Improves function and quality of life

A smaller, newer type of left ventricular assist device developed with continuous-flow technology is effective for at least six months and can improve function and quality of life while patients are awaiting a heart transplant, researchers report in the Aug. 30 issue of the New England Journal of Medicine.

Leslie W. Miller, M.D., from the University of Minnesota in Minneapolis, and colleagues implanted a continuous-flow pump (HeartMate II LVAD, made by Thoratec) in 133 patients who were on a waiting list for a heart transplant.

After six months, 75 percent of patients underwent transplantation, had cardiac recovery or continued to receive mechanical support while remaining eligible for transplantation. The device was used for a median of 126 days, with a survival rate of 68 percent at 12 months during support. After three months, functional status and quality of life significantly improved. Major adverse events included stroke, right heart failure, pump thrombosis, postoperative bleeding and percutaneous lead infection.

"A continuous-flow left ventricular assist device can provide effective hemodynamic support for a period of at least six months in patients awaiting heart transplantation, with improved functional status and quality of life," Miller and colleagues conclude.

The study was supported by Thoratec.

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Risk of Death Higher After Albumin for Brain Injury

Lower risk with saline resuscitation

Resuscitating traumatic brain injury patients with albumin instead of saline can increase the risk of death by nearly twofold, according to study findings published in the Aug. 30 issue of the New England Journal of Medicine.

John Myburgh, M.D., Ph.D., from ANZICS Clinical Trials Group in Carlton, Victoria, Australia, and colleagues randomized 460 patients with traumatic brain injury to resuscitation with albumin or saline. The 318 patients with Glasgow Coma Scale (GCS) scores of 3-8 were classified as having severe brain injury.

After 24 months, the researchers found that significantly more patients in the albumin group died (33.2 versus 20.4 percent, relative risk 1.63). Similar results were observed in patients with severe brain injury (41.8 versus 22.2 percent, relative risk 1.88). Fewer patients with a GCS score of 9-12 treated with albumin died (16 versus 21.6 percent, relative risk 0.74), though this was not statistically significant.

"In this post-hoc study of critically ill patients with traumatic brain injury, fluid resuscitation with albumin was associated with higher mortality rates than was resuscitation with saline," Myburgh and colleagues conclude.

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Hypogonadism Reversal After Halting Hormone Treatment

Patients should periodically discontinue treatment to assess their hormone secretion

Because hypogonadism can spontaneously reverse, patients undergoing hormonal therapy for the condition should periodically discontinue treatment to assess if their own gonadotropin secretion has normalized, according to two studies published in the Aug. 30 issue of the New England Journal of Medicine.

Nelly Pitteloud, M.D., from Massachusetts General Hospital in Boston, and colleagues identified 15 men with absent or partial puberty whose idiopathic hypogonadotropic hypogonadism reversed after hormonal treatment and was sustained after discontinuing treatment. This included five prospectively identified men out of 50 with the disorder. The men had significant increases in serum testosterone, luteinizing hormone, follicle-stimulating hormone and testicular volume.

Adriana Lofrano-Porto, M.D., from University Hospital of Brasilia, and colleagues describe three siblings (two men, one woman) with hypogonadism due to a deficiency of luteinizing hormone. The siblings had a homozygous mutation in the luteinizing hormone beta-subunit gene, which disrupted the splicing of the gene and led to a lack of hormone secretion. The woman had normal pubertal development, but secondary amenorrhea and infertility.

Many of these patients spontaneously undergo puberty, states the author of an accompanying editorial, adding that patients "should periodically undergo a brief discontinuation of hormonal therapy to assess whether their endogenous gonadotropin secretion has normalized."

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Long-Term Health Good in Rabies Patient Treated by Coma

Few physical, no mental difficulties after induced coma and antiviral agents

A 15-year-old girl treated with induced coma and antiviral agents after contracting rabies is in good health more than two years later, with few physical and no mental difficulties, according to a letter to the editor published in the Aug. 30 issue of the New England Journal of Medicine.

William T. Hu, M.D., Ph.D., from the Mayo Clinic College of Medicine in Rochester, Minn., and colleagues describe the 27-month follow-up of a 15-year-old girl who developed rabies encephalitis in 2005 after being bitten by a rabid bat. She recovered after being treated with a regimen that included ketamine, ribavirin and amantadine, and induced coma.

The researchers found that the patient still had fluctuating dysarthria, gait difficulties and the occasional feeling of cold in the feet. She had no difficulty with normal daily activities including driving, took several college-level courses, scored well on a national college achievement test, graduated from high school and planned to attend college.

"The combined treatment with antiexcitatory agents (ketamine, midazolam and phenobarbital) and antiviral agents (ketamine, amantadine and ribavirin) used by Willoughby et al. [the authors of the original report describing the girl's case] may have contributed to this patient's favorable outcome, and such treatment warrants further evaluation," Hu and colleagues conclude.

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