Medical Students Favor Lifestyle Over Money in Choice of Specialty

By Ben Klayman

CHICAGO (Reuters) Sept 02 - An increasing number of medical students are picking their specialty based on the lifestyle it permits, including more time to spend with family, rather than such traditional factors as pay and prestige, according to a study published in the September 3 issue of the Journal of the American Medical Association.

"We're being told essentially that it's not the number of hours or the intensity of the work, it's the ability at the end of the day to close out the work day and go home and be away from professional responsibilities," Dr. Gregory Rutecki, one of the study's authors, said.

"The trend may also represent the increasing number of women in the profession," who seek a closer balance between family and professional duties, Dr. Rutecki said.

The finding points to potential shortages of doctors in specialties such as family practice, surgery, and obstetrics, as medical students shun fields where they are required to be on-call during many off hours, the report said.

"We're going to have person-power shortages in the next 10 years in critical areas. Where are the primary care doctors going to come from?" said Dr. Rutecki, a professor at Northwestern University.

The report said previous studies have also detected the trend, with students more inclined to select specialties with fewer work hours per week and fewer nights on-call.

Researchers collected 6 years of data from matching programs that direct graduating medical students to hospital residencies in their chosen specialties. Programs offering defined hours gained in favor over that period.

From 1996 to 2002, the percentage of students surveyed who chose anesthesiology grew to 6.4% from 1.1%; dermatology was picked by 2.3%, up from 0.2%: and radiology was chosen by 6.1% in 2002 versus 3.3% in 1996.

On the other hand, 9.5% chose family practice in 2002 compared to 16.1% in 1996, and 7.6% chose general surgery versus 10.4% six years earlier.

Over the study period, 55% of students' choices related to lifestyle factors, compared to 9% basing their decisions on potential income.

The increasing number of women doctors and general practitioners' loss of decision-making to insurance companies will likely exacerbate the trend, Dr. Rutecki said.

JAMA 2003;290:1173-1178,1179-1182.

Cough-CPR Proposed as New Technique for at-Home Resuscitation

Peggy Peck

Sept. 3, 2003 (Vienna) — The developer of a novel approach to cardiopulmonary resuscitation (CPR) in cardiac arrest, a program called Cough-CPR, claims that with specific training, patients at risk for sudden cardiac death can be trained to initiate a cough protocol that will preserve consciousness until medical help arrives — but other cardiologists are not convinced.

Tadeusz K. Petelenz, MD, professor of cardiology at the Cardiological Foundation, Silesian Medical School, in Katowice, Poland, said that his study of 115 patients with a history of cardiac arrest symptoms successfully used the Cough-CPR strategy in 365 cases of perceived prodromal symptoms of fainting. "And symptoms disappeared in 292 cases," he told Medscape. Dr. Petelenz presented his findings Wednesday at the European Society of Cardiology (ESC) Congress 2003 and discussed them during an ESC press conference Tuesday.

Coughing can support circulation when the heart is in ventricular fibrillation because coughing causes "abrupt upswings of pressure in the thorax and abdomen" that act much like external CPR, he said.

To demonstrate the effect, he asked a London-based reporter attending the press conference to find her pulse. "Now cough and feel the difference." The journalist said she did feel a difference in her pulse.

He describes his program this way: the patient is trained to cough every one to two seconds in bouts of five coughs. This process is repeated in regular morning and evening training sessions until the patient can cough for as many as 10 to 30 coughs in each bout. But learning the cough is only one part of the program — patients are also taught to recognize symptoms of sudden cardiac arrest: shortness of breath, sudden nausea, dizziness, inappropriate sweating, blurred vision, sudden weakness, and trembling hands.

To prove his point, Dr. Petelenz taught 115 patients who have a history of cardiac arrest symptoms to recognize the symptoms and initiate coughing. The patients used the cough in "365 instances of perceived [warning] symptoms of fainting. As a result, symptoms disappeared in 292 cases and only 73 cases needed additional medical assistance," he said. Moreover, all the patients "survived until follow-up therapy was initiated. Only 73 patients needed additional treatment; those treatments included pacemakers, corrective surgery, and medical therapy."

Dr. Petelenz, who carries stacks of pamphlets that describe the Cough-CPR program, said he wants community organizations to teach his program just as CPR is taught.

But Leo Bossaert, MD, executive director of the European Resuscitation Council and professor of medicine at University Hospital Antwerp in Belgium, was openly skeptical and said he would need to "see evidence before I could recommend Cough-CPR."

He said the Petelenz study failed to offer convincing evidence — "there is no control group and we don't even know if these patients had true cardiac arrest."

Dr. Bossaert said he is not questioning the pathophysiology because he agrees that cough can be used to keep a patient conscious. "We've been doing this for years in the cath lab," he said. But he noted that the cath lab is much different than "a patient's home."

Given the lack of evidence, Dr. Bossaert said it would be irresponsible to recommend Cough-CPR training now. He also worries that introducing a program like Cough-CPR could confuse the public, which would further delay treatment. "We don't want someone to be coughing rather than dialing the emergency number," he said.

ESC Congress 2003: Abstract 3751. Presented Sept. 3, 2003.

Reviewed by Brunilda Nazario, MD

Green Tea Appears to Protect Against Breast Cancer

NEW YORK (Reuters Health) Sept 02 - Among Asian-American women, consumption of green tea is associated with a reduced risk of breast cancer, according to a report in the September 10th issue of the International Journal of Cancer.

In a population-based, case-control study, Dr. Anna H. Wu, of the University of Southern California, Los Angeles, and colleagues examined the consumption of green tea among 501 Asian-American women with breast cancer and 594 matched controls. The investigators also collected data on menstrual and reproductive factors, dietary habits, and other lifestyle factors.

There was no association between consumption of black tea and the risk of breast cancer. Green tea, however, was associated with a significant reduction of breast cancer risk. This association was maintained after adjustments for age, specific Asian ethnicity, birthplace, age at menarche, parity, menopausal status, use of hormones, body size, and intake of total calories.

"Compared to women who did not drink tea (either black or green) regularly (i.e., less than once a month), risk of breast cancer was lowest among those who drank green tea only (odds ratio = 0.57), intermediate among those who drank both green and black tea (odds ratio = 0.69), and unchanged among those who drank black tea only (odds ratio = 1.00) after adjustment for the covariates mentioned above," Dr. Wu and colleagues report.

The inverse relationship between breast cancer risk and green tea consumption remained significant after adjusting for smoking; intake of alcohol, coffee, black tea, soy, and dark green vegetables; family history of breast cancer; and physical activity, according to the investigators.

Both green tea and soy intake were significantly and independently protective against breast cancer. However, the beneficial effect of green tea was primarily observed among those who consumed low levels of soy, and the beneficial effect of soy were primarily observed among those who did not drink green tea.

"In conclusion, our study shows that green tea may act as a chemopreventive agent against breast cancer development," the researchers write.

Int J Cancer 2003;106:574-579.

Researchers Call for Higher Use of ACE Inhibitors

By Ben Hirschler

VIENNA (Reuters) Sept 01 - All coronary disease patients should be considered for treatment with an ACE inhibitor, which has the potential of preventing hundreds of thousands of deaths, researchers said Sunday.

Professor Kim Fox of the Royal Brompton Hospital in London told the annual meeting of the European Society of Cardiology that new clinical trial data showed the clear benefits of adding an ACE inhibitor to therapy regimens that include aspirin and a statin.

The so-called Europa study found patients given the ACE inhibitor perindopril, in addition to standard treatment, had a 20 percent lower risk of cardiovascular death, heart attack and cardiac arrest.

"We are going to make a major recommendation here. We are asking the government authorities to consider giving perindopril to all people with coronary disease," Fox told reporters.

Perindopril, one of a number of rival drugs with the same mode of action, is sold under the brand Coversyl by privately owned French firm Servier, which funded the four-year study involving more than 12,000 patients -- the largest of its kind.

MILESTONE

Fox, who co-chaired the study, said the results were a "milestone in cardiology," proving for the first time the life-saving benefits of an ACE inhibitor in a broad range of patients.

In a country the size of Britain, with a population of 60 million, adding perindopril to standard therapy would stop 100,000 heart attacks or cardiovascular deaths over a four-year period, he added.

"I think governments will respond in the same way they did with statins" which are now widely used as a preventative treatment, he added.

Previous research, published four years ago, had shown the benefits of another ACE inhibitor, Aventis SA's ramipril or Altace, in coronary disease patients over 55 years old with high-risk conditions such as diabetes.

But this is the first time the benefits of the drug class have been proven across all patients with the disease. Many of those enrolled in the Europa study had no symptoms.

Professor Maarten Simoons of the Thoraxcenter Erasmus Medical Center in Rotterdam said it was too early to assess cost-effectiveness, but he noted ACE inhibitors were typically half the price of statins. Statin drugs, such as Pfizer Inc.'s Lipitor, cost around 600 euros per patient a year in the Netherlands.

ACE inhibitors work by inhibiting angiotension converting enzyme, which plays a crucial role in the production and breakdown of various chemicals involved in blood pressure regulation.

In addition, however, they can also improve heart and blood vessel wall structure and function, preventing vessel constriction and suppressing unnecessary blood clotting.

Dietary Trans Fatty Acids Increase Small, Dense LDL Particles

Laurie Barclay, MD

Sept. 2, 2003 — Consumption of dietary trans fatty acids (FAs) is associated with a deleterious increase in small, dense low-density lipoprotein (LDL) cholesterol particles, according to the results of a study published in the September issue of the American Journal of Clinical Nutrition. This finding further reinforces the importance of promoting diets low in trans FAs to improve the lipoprotein profile.

"Dietary trans FAs, which are formed during the process of hydrogenating vegetable oil, are known to increase plasma LDL-cholesterol concentrations," write Jean-François Mauger, from Laval University in Quebec, Canada, and colleagues. "Accumulating evidence indicates that the size of LDL particles confers an independent risk, with small and dense particles being more atherogenic than are larger, less dense particles."

In this study, 18 women and 18 men each consumed five different experimental diets in random order for 35-day periods. In each diet, fat accounted for 30% of total energy intake. However, the diets differed in fat composition, with two thirds of the fat in the form of semiliquid margarine (0.6 g trans FAs/100 g fat), soft margarine (9.4 g trans FAs/100 g fat), shortening (13.6 g trans FAs/100 g fat), stick margarine (26.1 g trans FAs/100 g fat), or butter, which was low in trans FAs (2.6 g trans FAs/100 g fat) but rich in saturated fat. Polyacrylamide gradient gel electrophoresis identified LDL particle size and distribution.

With increasing amounts of dietary trans FAs, LDL particle size decreased significantly and in a dose-dependent fashion compared with LDL particle size seen with the butter-enriched diet (P < .001). Cholesterol concentration in large (>260 Å) and medium (255?260 Å) size LDL particles also increased proportionately to the amount of trans FAs in the diet.

"Interestingly, compared with the four diets enriched in trans fatty acids, the diet enriched with saturated fat (butter) was associated with the highest plasma LDL-cholesterol concentrations but, paradoxically, the largest LDL particles," the authors write. "These data reinforce the importance of promoting diets that are low in saturated fat and that contain a minimal quantity of trans fatty acids from hydrogenated fat in order to favorably affect the lipoprotein profile and thus contribute to a reduced risk of cardiovascular disease."

The authors report no potential conflicts of interest in this study.

Am J Clin Nutr. 2003;78(3):370-375

Reviewed by Brunilda Nazario, MD

Chromium Supplements Appear to Improve Glucose Sensitivity in Diabetics

Ed Susman

Aug. 29, 2003 (Paris) — The dietary supplement chromium picolinate may help patients with type 2 diabetes control their disease, according to a series of presentations here at the 18th International Diabetes Foundation Congress.

The presentations described the genetic and molecular mechanisms of how chromium picolinate reduces glucose resistance, as well as how the supplement can reduce glucose levels.

"I'm not diabetic," said Dr. Zhong Wong, MD, research assistant professor at the University of Vermont in Burlington, "but I sometimes have higher glucose levels that I want. I have been taking chromium myself because I think it helps."

Dr. Wong used gene microarray GeneChip technology from Affymetrix to determine which genes are upregulated and downregulated in human skeletal muscle. "That gene expression analysis suggests that chromium picolinate may down-regulate genes in human skeletal muscle that are potentially involved in cellular insulin action, specifically tumor necrosis factor (TNF)AIP6 and ubiquitin-associated proteins," he said those proteins are implicated in dysfunctional insulin production.

"We think that chromium picolinate can influence a person's diabetic treatment so that levels of insulin required may be reduced," he said.

In another presentation, researchers from the Netherlands studied the effects of chromium picolinate intake on metabolic control in 52 patients with type 2 diabetes, in a double-blind, placebo-controlled study. The six-month study enrolled patients who had hemoglobin (HbA1c) levels greater than 8 percent and were prescribed more than 50 IU of insulin per day. In addition to their usual oral antidiabetic medication, patients were also given 500 µg chromium picolinate, 1,000 µg chromium picolinate per day, or placebo.

S. T. Houweling, MD, from the department of internal medicine at Isala Clinic's Weezenlanden office in Zwolle, found a significant decrease in HbA1c levels in the group receiving higher doses of chromium picolinate supplements. HbA1c levels decreased from 9.5% to 9% during a six-month period in patients receiving a higher dose of the supplement, a difference that was statistically significant (P = .032). The study also showed a significant reduction in cholesterol levels and trends for improvement in triglycerides in both chromium picolinate groups as well as a reduction in blood pressure in all groups.

"Chromium treatment lowered HbA1c and improved the lipid profile in patients with type 2 diabetes in poor metabolic control in a Western society," he said in his poster presentation. But the study did not reveal significant differences between the chromium groups and those who took placebo.

The failure to show differences between the placebo and chromium groups is not surprising, said Amanda Adler, MD, a clinician and epidemiologist at the University of Oxford in the U.K. "When people are in clinical trials, they tend to recognize that they are being watched closely by their doctors and nurse, so they take their medicine when they are supposed to and they try to stay on proper diets," she said.

Dr. Adler suggested that behavior by the patients receiving placebo might have blunted the true differences between treatment effects of chromium compared with placebo.

In another study from the Vermont group, William Cefalu, MD, said his study in human subjects appears to confirm Dr. Wong's work in the laboratory. "This study demonstrates that those individuals with type 2 diabetes who supplemented their diet with chromium picolinate had an enhanced activity of the protein compared to those who were on placebo," he said.

The double-blind, placebo-controlled trial studied patients with type 2 diabetes treated with sulfonylureas or a diet program. Both groups were randomized to receive either 1,000 µg chromium picolinate daily or placebo. Of the 16 subjects, those randomized to chromium picolinate had a mean increase in insulin sensitivity of 8.9%, while the placebo group had a mean decrease of 3.6%.

The researchers suggest that the potential in vivo mechanism of chromium picolinate on insulin action may be by increasing the activation of Akt phosphoration, an intracellular insulin-dependent protein that facilitates the uptake of glucose into cells.

"As this intracellular pathway is implicated in contributing to insulin resistance, this represents a possible mechanism to explain chromium picolinate's beneficial effect on insulin sensitivity as observed in several clinical studies," Dr. Cefalu said.

Dr. Wong suggested that one reason chromium supplementation improves insulin's action is that it alleviates dietary chromium deficiency. In addition to over-the-counter products, chromium can be found in nuts and in red meat. Dr. Wong said that in general the supplements do not cause adverse effects aside from infrequent and mild gastrointestinal discomfort.

The University of Vermont studies were supported by grants from Nutrition 21, a marketer of chromium.

18th IDF Congress: Abstracts 154, 756, 762. Presented Aug. 28, 2003.

Reviewed by Brunilda Nazario, MD

Ed Susman is a freelance writer for Medscape.

Chromium Supplements Appear to Improve Glucose Sensitivity in Diabetics

Ed Susman

Aug. 29, 2003 (Paris) — The dietary supplement chromium picolinate may help patients with type 2 diabetes control their disease, according to a series of presentations here at the 18th International Diabetes Foundation Congress.

The presentations described the genetic and molecular mechanisms of how chromium picolinate reduces glucose resistance, as well as how the supplement can reduce glucose levels.

"I'm not diabetic," said Dr. Zhong Wong, MD, research assistant professor at the University of Vermont in Burlington, "but I sometimes have higher glucose levels that I want. I have been taking chromium myself because I think it helps."

Dr. Wong used gene microarray GeneChip technology from Affymetrix to determine which genes are upregulated and downregulated in human skeletal muscle. "That gene expression analysis suggests that chromium picolinate may down-regulate genes in human skeletal muscle that are potentially involved in cellular insulin action, specifically tumor necrosis factor (TNF)AIP6 and ubiquitin-associated proteins," he said those proteins are implicated in dysfunctional insulin production.

"We think that chromium picolinate can influence a person's diabetic treatment so that levels of insulin required may be reduced," he said.

In another presentation, researchers from the Netherlands studied the effects of chromium picolinate intake on metabolic control in 52 patients with type 2 diabetes, in a double-blind, placebo-controlled study. The six-month study enrolled patients who had hemoglobin (HbA1c) levels greater than 8 percent and were prescribed more than 50 IU of insulin per day. In addition to their usual oral antidiabetic medication, patients were also given 500 µg chromium picolinate, 1,000 µg chromium picolinate per day, or placebo.

S. T. Houweling, MD, from the department of internal medicine at Isala Clinic's Weezenlanden office in Zwolle, found a significant decrease in HbA1c levels in the group receiving higher doses of chromium picolinate supplements. HbA1c levels decreased from 9.5% to 9% during a six-month period in patients receiving a higher dose of the supplement, a difference that was statistically significant (P = .032). The study also showed a significant reduction in cholesterol levels and trends for improvement in triglycerides in both chromium picolinate groups as well as a reduction in blood pressure in all groups.

"Chromium treatment lowered HbA1c and improved the lipid profile in patients with type 2 diabetes in poor metabolic control in a Western society," he said in his poster presentation. But the study did not reveal significant differences between the chromium groups and those who took placebo.

The failure to show differences between the placebo and chromium groups is not surprising, said Amanda Adler, MD, a clinician and epidemiologist at the University of Oxford in the U.K. "When people are in clinical trials, they tend to recognize that they are being watched closely by their doctors and nurse, so they take their medicine when they are supposed to and they try to stay on proper diets," she said.

Dr. Adler suggested that behavior by the patients receiving placebo might have blunted the true differences between treatment effects of chromium compared with placebo.

In another study from the Vermont group, William Cefalu, MD, said his study in human subjects appears to confirm Dr. Wong's work in the laboratory. "This study demonstrates that those individuals with type 2 diabetes who supplemented their diet with chromium picolinate had an enhanced activity of the protein compared to those who were on placebo," he said.

The double-blind, placebo-controlled trial studied patients with type 2 diabetes treated with sulfonylureas or a diet program. Both groups were randomized to receive either 1,000 µg chromium picolinate daily or placebo. Of the 16 subjects, those randomized to chromium picolinate had a mean increase in insulin sensitivity of 8.9%, while the placebo group had a mean decrease of 3.6%.

The researchers suggest that the potential in vivo mechanism of chromium picolinate on insulin action may be by increasing the activation of Akt phosphoration, an intracellular insulin-dependent protein that facilitates the uptake of glucose into cells.

"As this intracellular pathway is implicated in contributing to insulin resistance, this represents a possible mechanism to explain chromium picolinate's beneficial effect on insulin sensitivity as observed in several clinical studies," Dr. Cefalu said.

Dr. Wong suggested that one reason chromium supplementation improves insulin's action is that it alleviates dietary chromium deficiency. In addition to over-the-counter products, chromium can be found in nuts and in red meat. Dr. Wong said that in general the supplements do not cause adverse effects aside from infrequent and mild gastrointestinal discomfort.

The University of Vermont studies were supported by grants from Nutrition 21, a marketer of chromium.

18th IDF Congress: Abstracts 154, 756, 762. Presented Aug. 28, 2003.

Reviewed by Brunilda Nazario, MD

Ed Susman is a freelance writer for Medscape.

Heart Rate Recovery After Exercise Predicts Mortality, Independent of CAD Severity

By Anthony J. Brown, MD

NEW YORK (Reuters Health) Sept 03 - Even after accounting for the angiographic severity of coronary artery disease (CAD), heart rate recovery after exercise predicts mortality in patients with suspected CAD, new research shows.

"Several studies have looked at the predictive ability of heart rate recovery [HRR], but it was unclear if HRR was simply a reflection of underlying CAD," Dr. Michael S. Lauer, from the Cleveland Clinic Foundation, told Reuters Health. "We basically found that HRR is not a reflection of underlying CAD and that it is an independent marker for mortality risk."

The findings are based on a study of nearly 3000 consecutive patients who underwent exercise testing for suspected CAD. In all patients, a coronary angiogram was performed within 90 days of exercise testing.

Abnormal HRR was defined as a drop in heart rate of 12 beats or less in the first minute after exercise was completed. For patients who underwent stress echocardiography, a threshold of 18 beats or less was used.

The researchers' findings are published in the September 3rd issue of the Journal of the American College of Cardiology.

Nearly 30% of patients had abnormal HRR, yet only 14% had severe CAD on angiography, the researchers report.

Eleven percent of subjects died during 6 years of follow-up. Abnormal HRR and severe CAD were found to be predictors of mortality that provided additive prognostic information, the authors state.

On multivariate analysis, abnormal HRR and severe CAD were associated with a 60% and 40% increase, respectively, in the risk of death.

"Since our first report on HRR in 1999, I think use of this test has gradually increased in the medical community," Dr. Lauer noted. "It's so easy to do. It basically adds no cost and no effort to standard exercise testing."

Still, it remains to be determined "if improvements in HRR translate into improvements in outcome," Dr. Lauer said. "Our group is in the middle of a huge study looking into this," he added.

In a related editorial, Dr. Bernard R. Chaitman, from St. Louis University, comments that "a better understanding of how abnormal exercise heart rate responses result in an increased death rate could lead to newer therapeutic approaches that reduce the mortality risk."

J Am Coll Cardiol 2003;42:831-841.

Dutch Approve Cannabis as Prescription Drug

By Paul Gallagher

AMSTERDAM (Reuters) Sept 01 - The Netherlands Monday became the world's first country to make cannabis available as a prescription drug to treat cancer, HIV and multiple sclerosis patients, the Health Ministry said.

The Netherlands is making the drug widely available to chronically ill patients amid pressure on countries like Britain, Canada, Australia and the United States to relax restrictions on its supply as a medicine.

Dutch doctors will be allowed to prescribe it to treat chronic pain, nausea and loss of appetite in cancer and HIV patients, to alleviate MS sufferers' spasm pains and reduce physical or verbal tics in people suffering Tourette's syndrome.

"From September 1, 2003 pharmacies can provide medicinal cannabis to patients with a prescription from a doctor. Cannabis has a beneficial effect for many patients," the Health Ministry said.

The Netherlands, where prostitution and the sale of cannabis in coffee shops are regulated by the government, has a history of pioneering social reforms. It was also the first country to legalize euthanasia.

Two companies in the Netherlands have been given licenses to grow special strains of cannabis in laboratory-style conditions to sell to the Health Ministry, which in turn packages and labels the drug in small tubs to supply to pharmacies.

As well as pharmacies, 80 hospitals and 400 doctors will be allowed to dispense five-gram doses of SIMM18 medical marijuana for 44 euros ($48) a tub and more potent Bedrocan at 50 euros.

The Health Ministry recommends patients dilute the cannabis -- which will be in the form of dried marijuana flowers from the hemp plant rather than its hashish resin -- in tea or turn it into a spray.

HIV SUFFERERS WELCOME MOVE

A British drug firm pioneering cannabis spray medicine to give pain relief for multiple sclerosis patients is hoping to launch the product in Britain later this year.

The association of HIV patients in the Netherlands welcomed the government's move to make cannabis available in high-street pharmacies.

"We are glad the government recognizes that for some people it can improve the quality of life," said Robert Witlox, managing director of HIV Vereniging. The association has called on health insurers to cover the cost of the drug like any other.

The government, which recognized many chronically ill people were already buying cannabis from coffee shops, said it should only be prescribed by doctors when conventional treatments had been exhausted or if other drugs had side-effects.

The government said it would start distributing to pharmacies Monday. The Health Ministry's Office of Medicinal Cannabis has a monopoly on wholesale distribution of the drug, grown in laboratory-style conditions to ensure medicinal purity.

The ministry estimates up to 7,000 people in the Netherlands have used cannabis for medical reasons, buying it in coffee shops. It said this could more than double once it was available from pharmacies in pure medicinal form.

Cannabis has a long history of medicinal use. It was used as a Chinese herbal remedy around 5,000 years ago, while Britain's Queen Victoria is said to have taken cannabis tincture for menstrual pains.

But it fell out of favor because of a lack of standardized preparations and the development of more potent synthetic drugs.

Critics argue that it has not passed sufficient scientific scrutiny at a time when researchers are trying to determine if it confers the medical benefits many users claim. Some doctors say it increases the risk of depression and schizophrenia. ($1=.9145 Euro)

SARS Mortality May Be Higher Than Previously Thought

NEW YORK (Reuters Health) Sept 02 - Previous reports have estimated the mortality rate for SARS to be between 5% and 10%, but findings from a new study suggest that the rate could be as high as 12%.

The recent global outbreak of severe acute respiratory syndrome (SARS), which is caused by a coronavirus, began in southern China. Before being brought under control, thousands of SARS cases were reported, including several hundred fatalities.

In a study reported in the September 2nd online issue of the Annals of Internal Medicine, Dr. Sik To Lai, from Princess Margaret Hospital in Hong Kong, and colleagues analyzed data from 267 consecutive patients who were hospitalized between February 26 and March 31, 2003 for probable or confirmed SARS.

The patients included 227 with confirmed SARS and 40 with probable SARS, the authors note. Nearly all of the patients presented with fever. Other common symptoms included chills, malaise, and myalgia.

The most common laboratory finding, noted in 73% of patients, was lymphopenia, followed by thrombocytopenia, hyponatremia, and increased levels of lactate dehydrogenase and C-reactive protein.

During hospitalization, a rise in the rates of diarrhea, anemia, and acute renal failure was observed, the authors state. More than a quarter of patients required intensive care due to respiratory failure.

The 3-month mortality rate for the study group was 12%, the investigators note. On multivariate analysis, age older than 60 years and lactate dehydrogenase level > 3.8 kat/L were identified as independent predictors of mortality.

The current findings may have differed from previous ones, in part, because of how SARS cases were defined. In contrast to definitions used by the World Health Organization and the Centers for Disease Control and Prevention, the one used by Dr. Lai's team does not require the presence of respiratory symptoms for a SARS diagnosis.

In combating future SARS outbreaks in Hong Kong, the authors note, "we need to refine the current case definition, search for a reliable rapid diagnostic test, and explore effective and safe antiviral therapy."

Ann Intern Med 2003;139.

Clinical Context on D/D b/w Inhalational Anthrax and Viral infections

Inhalation anthrax is a rare, rapidly progressive, potentially fatal illness mediated by two toxins: an edema factor and a lethal factor. Classic findings include hemorrhagic mediastinitis and hemorrhagic meningitis. Anthrax is classified by the U.S. Centers for Disease Control and Prevention (CDC) as one of six "category A" bioterrorist agents posing the greatest civilian risk. Public health preparedness protocols and recommendations have been published that rely on rapid identification of at-risk individuals and dispensing prophylactic antibiotics. Because of the high volume of patients anticipated in such an attack, screening and triage protocols will need to rely on rapid case-finding methods that have high positive predictive value and result in effective use of limited hospital and healthcare resources. High sensitivity and specificity of screening methods are more likely to yield correct diagnoses.

The authors suggest that radiology and laboratory testing are not feasible in a mass bioterrorist event, and that assessment of presenting symptoms will be a first-line screening tool. This study systematically examines records of anthrax clinical case presentations from 1920 to 2001, compares the findings to presentations of common viral respiratory infections, and arrives at an evidence-based protocol for case detection and case exclusion, using available data.

Study Highlights

* A systematic literature search was performed using the MEDLINE and Web of Science databases with the keywords "anthrax" and "case report." Matching data on presentations of common viral respiratory tract infections were obtained from MEDLINE.
* Anthrax studies excluded from the review were asymptomatic cases that would not apply to a mass bioterrorist event screening scenario, anthrax in children, case reports on anthrax from the 1979 Russian outbreak (because of questionable validity and completeness of reports), and non-English language studies.
* 28 complete reports on anthrax (11 contemporary and 17 historical) were compared with 4,694 cases of influenza or other viral or community-acquired respiratory infection.
* PLRs and posttest probabilities were calculated with 95% confidence intervals. The posttest probability of having inhalational anthrax is influenced by both the magnitude of the PLR and the pretest probability of having anthrax (based on the level of threat to the community).
* Nonheadache neurologic symptoms such as loss of consciousness, confusion, blurred vision, and dizziness had the greatest positive predictive value (likelihood ratio cannot be calculated), followed by dypsnea (PLR, 5.3; CI, 3.7 - 7.4), nausea or vomiting (PLR, 5.1; CI, 3.0 - 8.5), and abnormal lung auscultation (PLR, 8.1; CI, 5.3 - 12.5).
* The most discriminating symptoms of negative predictive value were rhinorrhea (PLR, 0.2; CI, 0.1 - 0.4) and sore throat (PLR, 0.2; CI, 0.1 - 0.5), which are suggestive of viral infection.
* Mortality from inhalational anthrax was high for historical patients (16 of 17 patients died) compared with contemporary cases from the 2001 anthrax attacks (5 of 11 patients died).
* The suggested evidence-based screening protocol sequence is:
1. Identify patients with nonheadache neurologic symptoms (high PLR for diagnosis of inhalational anthrax) for highest need for inhalational anthrax assessment.
2. Identify patients with fever, chills, or cough. A negative response has high positive predictive value for exclusion of inhalational anthrax and such patients may be sent home with prophylactic antibiotics.
3. Screen patients with positive response to fever, chills, or cough for nausea or vomiting and dypsnea. Presence of any of these symptoms increases the likelihood of anthrax fivefold.
4. Perform lung auscultation. A positive finding increases the likelihood of having anthrax eightfold.
5. Remaining patients may be screened for rhinorrhea and sore throat. Absence of these symptoms in the presence of fevers and chills should prompt further referral; a positive finding increases the likelihood of having anthrax by fivefold.

Pearls for Practice

* Clinical presentation of nonheadache neurologic symptoms, dypsnea, nausea and vomiting, and abnormal lung auscultation are of high positive predictive value in screening for inhalational anthrax during a mass bioterrorist event.
* Presence of fevers, chills, or cough combined with absence of rhinorrhea and sore throat increases the likelihood of anthrax inhalation when anthrax exposure has occurred.

Clinical Context - Long term benfefit of Ciprofloxacin in treatment of Reactive Arthritis

Reactive arthritis represents a set of rheumatologic disorders related to a previous infection. Most of these responsible infections involve the gastrointestinal or genitourinary tracts, and causative organisms include Salmonella species, Shigella flexneri, Campylobacter jejuni, Yersinia species, and Chlamydia trachomatis. Most patients with reactive arthritis do not suffer long-term arthritis, but the authors of the current study report that 4% to 19% of affected patients will have a chronic course of the disease. Patients with the HLA-B27 gene are more likely to suffer long-term disease.

Attempts to use antibiotics to prevent long-term disease associated with reactive arthritis have met with poor results. Yli-Kerttula and colleagues, the authors of the current study, previously performed a similar trial of a three-month course of ciprofloxacin to improve the outcome of reactive arthritis. Published in the July 2000 issue of the Annals of the Rheumatic Diseases, they demonstrated that ciprofloxacin did not improve patients' self assessment, complete recovery, number of swollen joints, or erythrocyte sedimentation rate at one-year follow up. A similar trial by Sieper and colleagues, published in the July 1999 issue of Arthritis and Rheumatism, showed similar disappointing results for ciprofloxacin after three months of treatment and follow-up.

The current study evaluates the same group of patients from the original Yli-Kerttula study four to seven years later. The authors sought to determine if the ciprofloxacin therapy might carry forward some previously undiscovered positive effects on the course of reactive arthritis.
Study Highlights

* The original trial involved 71 participants with acute reactive arthritis. 60 subjects had arthritis induced by a gastrointestinal infection, and 11 patients had a previous genitourinary infection.
* Participants were randomized to receive either ciprofloxacin 500 mg or placebo twice a day for 3 months. They were followed for 1 year in the original trial and invited to be re-evaluated 4-7 years after randomization.
* Investigators were not blinded to the original treatment regimen of the study subjects.
* Primary outcome measures of the study included a clinical examination for swollen, painful joints, laboratory evaluation, including erythrocyte sedimentation rate and serum antibody levels against specific triggering pathogens, and radiographic evaluation via magnetic resonance imaging (MRI).
* 53 of the original 71 subjects were available for clinical analysis in the current study. 26 subjects were from the ciprofloxacin group, and 27 were from the placebo group. 85% of participants from the current study were HLA-B27 positive.
* 2 subjects in the ciprofloxacin group were found to have suspected inflammatory back pain on clinical examination compared with 7 patients in the placebo group. Overall, 2 patients (8%) in the ciprofloxacin group developed chronic rheumatic disease, while 11 patients (41%) in the placebo group had chronic rheumatic disease. This difference attained statistical significance.
* 10 of the 11 subjects in the placebo group with chronic rheumatic disease were HLA-B27 positive. Neither of the 2 ciprofloxacin-treated subjects with chronic disease were HLA-B27 positive.
* No particular microbe was an independent risk factor for chronic disease.
* Sacroiliitis was found on MRI in 3 patients in the placebo group but none in the ciprofloxacin group.
* 92% of subjects in the ciprofloxacin group had recovered according to the opinions of the examining physicians compared with 59% of the placebo group, a statistically significant difference. However, patients' assessment of their own recovery was similar between the 2 groups.
* There were no significant differences in laboratory findings between the 2 groups.

Pearls for Practice

* Reactive arthritis is caused by infection with certain bacteria and produce chronic symptoms in a minority of patients.
* Although previous research has demonstrated ciprofloxacin to be ineffective in preventing chronic symptoms related to reactive arthritis, the authors found some benefit four to seven years after ciprofloxacin treatment. More research will need to be conducted before a conclusion can be drawn on this controversial subject.

Studies Suggest Aspirin Resistance is More Common Than Once Believed

Peggy Peck

Sept. 4, 2003 (Vienna) — Two studies presented at the European Society of Cardiology Congress 2003 suggest that aspirin resistance is not only real, but also likely to be more common that once believed.

Robert Gabor Kiss, MD, PhD, from the National Center for Health Services in Budapest, Hungary, presented the finding that in Hungary "26.9% of the population is at risk for aspirin resistance." Thus, he said, it is shortsighted to rely on aspirin for secondary prevention.

This message was reiterated by Tina Poulsen, MD, PhD, a research fellow at Odense University Hospital in Denmark. Dr. Poulsen and colleagues took blood samples from patients admitted to her hospital with a suspected diagnosis of myocardial infarction (MI) and who were receiving aspirin therapy (150 mg/day) prior to admission. Blood from 298 patients was analyzed for "biochemical evidence of aspirin activity, that is, we measured platelet aggregation," she told Medscape.

Although all the patients were taking aspirin, "we could not find any evidence of aspirin biochemical activity in 36% of the patients with confirmed MI." And in patients who did not have an acute event, "19% had no evidence of aspirin activity," she said.

Dr. Kiss and colleagues also used a blood test to measure platelet aggregation and found similar results. They measured platelet reactivity in 2,275 patients — 2,215 patients receiving aspirin therapy, 100 to 325 mg/day, and 60 patients receiving ticlopidine 500 mg — and compared those results with platelet activity in blood samples taken from 150 MI or stroke survivors who were not receiving blood-thinning therapy. The patients were recruited at 10 participating centers.

Platelet activity was measured on a computerized Carat TX4 platelet aggregometer using fixed doses of different inductors (ADP 5 µM, collagen 2 µg/mL, epinephrine 10 µM, arachidonic acid 0.5 mM). The threshold of the measurable inhibition was defined as the mean of maximal aggregation percentage minus 2 standard deviations of the maximal values in the untreated controls. The patients were considered resistant if the results of their maximal aggregation were higher than the predetermined threshold.

Of 2,215 patients with cardiovascular disease taking aspirin alone for secondary prevention, 596 (26.9%) showed resistance compared with 4 of 60 ticlopidine patients, Dr. Kiss said.

Although both Drs. Kiss and Poulsen said they were convinced that aspirin resistance is real, both believe it is too soon to recommend universal testing to determine aspirin resistance. Moreover, Dr. Poulsen said that even if a patient is aspirin resistant by platelet aggregation measures, she "would not stop the aspirin because we really don't know if other activity of aspirin — for example, anti-inflammatory activity — could provide protection."

Freek W. A. Verheugt, MD, PhD, professor of cardiology at University Medical Center in Nijmegen, the Netherlands, told Medscape that there is a certain logic to the concept of aspirin resistance since "we have patients on aspirin and yet they have a second event. That suggests some resistance or some reason that aspirin is not enough to stop the thrombotic activity."

But Dr. Verheugt, who was not involved in the study, agreed that it would be premature to order lab tests for all aspirin patients, because "we don't have enough information. For example, perhaps something else is interfering with the aspirin." He noted that there are data to suggest that nonsteroidal anti-inflammatory drugs can interfere with aspirin's antiplatelet action and "smoking also blunts the effect of aspirin."

Nonetheless, he said that if patients have "recurrent events while on aspirin, it would be prudent to consider tailoring the therapy to add another antiplatelet."

ESC Congress 2003: Abstracts 2007, 2008. Presented Sept. 1, 2003.

Reviewed by Brunilda Nazario, MD