In the News
for the Week of 6-16-09
- Experts recommend using A1c to diagnose diabetes
- Low glucose not the problem, say ACCORD researchers
- MKSAP quiz: prostate cancer survival
- Longer androgen suppression boosts prostate cancer survival
Screening and assessment
- New self-screening test detects 93% of Alzheimer's cases
Annals of Internal Medicine
- Calcium has no weight-loss benefit for obese patients
- Lowering LDL cholesterol in statin-intolerant patients
- Study looks at establishing an upper age limit for colonoscopy
- Stents ineffective, potentially dangerous for renal function
- Skin sanitizers recalled due to presence of bacteria
- Class 1 recall for certain Medtronic pacemakers
From ACP Internist
- ACP Internist blog hosts Grand Rounds
Cartoon caption contest
- Put words in our mouth
Physician editor: Darren Taichman, ACP Member
Experts recommend using A1c to diagnose diabetes
An international committee of experts has called for the A1c assay to become the recommended method for diagnosing diabetes.
The committee included members of the American Diabetes Association, the European Association for the Study of Diabetes and the International Diabetes Federation. Their report, which was published online last week and appears in the July Diabetes Care, reviews the advantages of A1c testing over fasting glucose testing or two-hour glucose-tolerance testing. With current technology, A1c tests are as accurate and precise as the other measures, and provide a better index of overall glycemic exposure and risk for long-term complications, the experts said.
The report recommended that patients with an A1c of 6.5% or higher be diagnosed with diabetes, although the experts warned that the cutoff point is not absolute. Patients with A1c between 6.0% and 6.5% should be considered at highest risk of developing diabetes and receive demonstrably effective interventions, the committee said. They selected the cutoffs based on research showing the relationship between higher A1cs and retinopathy.
The use of retinopathy as the sole outcome is one potential problem with the recommendations, said the authors of an accompanying editorial. Additionally, the 6.5% threshold may be difficult to square with the 7% treatment target in current guidelines. Under the proposed system, there would also be controversy over the point at which to initiate metformin treatment, the editorial authors said.
The editorialists did conclude that the adoption of the A1c as a diagnostic criterion is reasonable. According to the international committee, the report is intended to serve as a stimulus to the international community and professional organizations to consider the use of A1c for diabetes diagnosis. It represents the views of its expert authors, but not necessarily the organizations that appointed them to the committee..
Low glucose not the problem, say ACCORD researchers
Neither low A1c levels nor hypoglycemia were to blame for the increased deaths found in the intensive control arm of the ACCORD trial, according to follow-up data from the study.
At the American Diabetes Association's Scientific Sessions last week, researchers presented new information about the excess deaths that occurred among patients with an A1c target under 6%. Last year, the study had reported a 20% increased death in the intensive control arm compared with patients with a target of 7% to 7.9%. However, additional analyses reported in a meeting press release found that patients who had a greater decline in A1c actually had a lower risk of death. An A1c under 7% was not a predictor of mortality risk, and for every 1% a patient's A1c increased over 6%, there was a 20% higher risk of death, the researchers reported.
Patients who had severe hypoglycemia during the trial were more likely to die, a separate analysis found. But patients in the intensive group who had hypoglycemia were less likely to die than those in the standard group who developed it. Although 7% of the 451 patients who died during the study had at least one severe hypoglycemic event, researchers identified only one case where the hypoglycemia definitely played a role in a patient's death. They theorized that patients in the intensive arm may have better learned how to recognize and treat hypoglycemia because they had more frequent episodes and greater interaction with providers.
ACCORD study authors said they are continuing to look for causes of the increased mortality. Although part of the trial was halted when the excess deaths were reported, the study has continued and will end June 30. Complete analyses, which also include research on blood pressure and lipid control, should be completed within the next year.
MKSAP quiz: prostate cancer survival
A 63-year-old man is evaluated during a routine examination. His medical history is noncontributory, and his family history is unremarkable.
Physical examination, including digital rectal examination, is normal. Laboratory studies include a serum prostate-specific antigen measurement of 4.2 ng/mL (4.2 μg/L). Biopsy of the prostate reveals adenocarcinoma with a Gleason score of 6 (3 + 3) (moderately differentiated) in two of the twelve cores obtained. Treatment options and the associated risks and benefits are discussed with the patient. The patient decides to undergo radical prostatectomy, during which a Gleason score of 8 (5 + 3) (poorly differentiated) is confirmed, with no evidence of disease in the lymph nodes.
Which of the following variables is likely to have the greatest impact on the patient's survival?
B) Lack of family history of prostate cancer
C) Gleason score
D) Asymptomatic at diagnosis
Click here or scroll to the bottom of the page for the answer and critique.
Longer androgen suppression boosts prostate cancer survival
Three years of androgen suppression after radiotherapy to treat locally advanced prostate cancer provides modestly better survival than six months of the hormone regimen, a European study concluded.
Because long-term androgen suppression can reduce the quality of life and increase the risk of fatal myocardial infarction, fractures and metabolic syndrome, researchers sought to examine the efficacy of short-term therapy. They studied men with locally advanced prostate cancer who had received external-beam radiotherapy plus six months of androgen suppression. Androgen suppression consisted of complete androgen blockade with a luteinizing hormone-releasing hormone (LHRH) analogue and an antiandrogen agent (daily 750 mg of flutamide or 50 mg of bicalutamide). Next, researchers randomized 970 men to two groups. The first (n=483) stopped treatment and the second (n=487) continued 2.5 more years of the LHRH analogue but not the antiandrogen. Researchers reported results in the New England Journal of Medicine.
After a median follow-up of 6.4 years, 132 patients in the short-term group and 98 in the long-term group died. The number of deaths due to prostate cancer was 47 in the short-term group and 29 in the long-term group. The five-year overall mortality was 19.0% for the short-term group and 15.2% for the long-term group. For prostate-specific mortality, the five-year cumulative rate was 4.7% in the short-term group (95% confidence interval [CI], 2.7 to 6.7) and 3.2% in the long-term group (95% CI, 1.6 to 4.8). Prostate-cancer-specific survival curves were significantly different (HR, 1.71; 95% CI, 1.14 to 2.57; P=0.002).
Although researchers termed the difference in the effect of short-term and long-term androgen suppression as modest, they continued that the advantage of long-term suppression is likely to be maintained at 10 years.
Screening and assessment.
New self-screening test detects 93% of Alzheimer's cases
A new self-administered screening test can accurately detect Alzheimer's disease in 93% of patients, a new study found.
Researchers assigned the TYM, or "Test Your Memory" test, to 540 control subjects age 18-95 years, and to 139 subjects attending a memory clinic. Of the latter group, 108 had Alzheimer's disease/amnestic mild cognitive impairment, and 31 had non-Alzheimer's degenerative dementias. The test involved performing a series of 10 tasks including calculation, naming, recall of a copied sentence, semantic knowledge and verbal fluency. It was designed to take minimal operator time, test a range of cognitive functions, and be sensitive to mild Alzheimer's disease. The top score was 50, including five points for the ability to do the test.
Control subjects scored 47 out of 50, on average, while patients with Alzheimer's disease scored an average of 33 out of 50. A score of 42 or less had a sensitivity of 93% and a specificity of 86% in diagnosing Alzheimer's disease, making the TYM more sensitive in detecting Alzheimer's than the mini-mental state examination, which has a 52% detection rate. The negative and positive predictive values of the TYM with a cutoff of 42 or less were 99% and 42%, with a prevalence of Alzheimer's disease of 10%. The study was published in the June 9 online British Medical Journal.
Advantages of the TYM over current bedside cognitive tests include the fact that a nurse was able to score the sheets as accurately as a specialist after 10 minutes training; it has excellent inter-rater agreement, and it is highly sensitive to Alzheimer's disease, the authors said. An editorial pointed out, however, that some items probably show cultural bias, and that people with visual impairment may have difficulty doing the test. The test should be validated in a range of settings and different populations before it is adopted widely, the editorial said.
Annals of Internal Medicine.
Calcium has no weight-loss benefit for obese patients
Researchers studied 340 overweight and obese patients to determine whether calcium supplementation might prevent weight gain or promote weight loss. The investigators weighed each participant and then randomly assigned half of them to take calcium pills (1,500 mg/d) and the other half to placebo. After two years, researchers found no difference in body weight, body mass index or body fat mass between the two groups. The researchers conclude that while calcium supplementation has health benefits, it is unlikely to prevent weight gain in overweight or obese patients..
Lowering LDL cholesterol in statin-intolerant patients
Sixty-two patients with abnormal LDL cholesterol levels and a history of statin intolerance were randomly assigned to either 1,800 mg a day of red yeast rice supplementation or placebo. Patients in both groups were enrolled in a therapeutic lifestyle change program that included weekly 3.5 hour meetings and education on cardiovascular disease, nutrition, exercise and relaxation techniques. The researchers checked LDL and total cholesterol levels in both groups at 12 and 24 weeks. They found that both cholesterol levels improved more in the red yeast rice group than in the placebo group. Pain, creatinine phosphokinase and liver enzyme levels did not differ between the groups..
Study looks at establishing an upper age limit for colonoscopy
Researchers looked at a random sample of 53,220 Medicare beneficiaries age 66 to 95 who underwent outpatient colonoscopy. Those patients were matched with individuals who did not have colonoscopy and then assessed at 30 days to determine the rate of cardiac and gastrointestinal events. Rates of adverse events following colonoscopy were low, but were greater in patients who had polyps removed, or had specific, common comorbid conditions. Adverse events also increased with age, another reason for establishing an upper age limit for colonoscopy..
Stents ineffective, potentially dangerous for renal function
Researchers studied 140 patients with atherosclerotic renal artery stenosis (ARAS) and impaired renal function to determine if stenting could help. They randomly assigned patients to medical treatment plus stenting or medical treatment only and followed them over a two-year period. Medical treatment consisted of antihypertensive treatment, a statin and aspirin. The researchers found that stent placement with medical treatment had no clear effect on progression of impaired renal function but led to a small number of significant procedure-related complications, including two deaths. The researchers conclude that stenting is not a safe or effective treatment for patients with ARAS and impaired renal function. They suggest that physicians treat these patients using a conservative therapeutic approach that focuses on managing cardiovascular risk factors.
Skin sanitizers recalled due to presence of bacteria
Several brands of skin sanitizer and skin protectant made by Clarcon Biological Chemistry Laboratory Inc. are being recalled, as high levels of disease-causing bacteria were found in the products during recent inspection, an FDA press release said.
Some of the bacteria found in the analyzed samples can cause opportunistic infections of the skin and underlying tissues which may require medical attention, and/or result in permanent damage. This is of particular concern because the products are promoted as antimicrobial agents that claim to treat open wounds and damaged skin, and to protect against various infectious diseases, the FDA said.
Following are products affected by the recall: Citrushield Lotion, Dermasentials DermaBarrier, Dermassentials by Clarcon Antimicrobial Hand Sanitizer, Iron Fist Barrier Hand Treatment, Skin Shield Restaurant, Skin Shield Industrial, Skin Shield Beauty Salon Lotion, Total Skin Care Beauty and Total Skin Care Work. All products should be discarded..
Class 1 recall for certain Medtronic pacemakers
A Class 1 recall is in effect for some Medtronic Kappa and Sigma pacemakers, which may fail due to a separation of wires that connect the electronic circuit to other pacemaker components, an FDA news release said.
Subject to recall are the Kappa Series 600/700/900 and Sigma Series 100/200/300. Patients with these models of Kappa and Sigma pacemakers should determine if their pacemaker is part of this recall by contacting Medtronic at 800-505-4636 or going to their Web site. About 21,000 pacemakers are affected by the recall, most of which have been implanted in patients for at least five years, the FDA said.
Patients with malfunctioning pacemakers may experience symptoms associated with abnormal heart rate, such as fainting or lightheadedness. In rare cases, pacemaker-dependent patients may experience serious injury or die.
From ACP Internist.
ACP Internist blog hosts Grand Rounds
ACP Internist hosts Grand Rounds, a weekly summary of the best health blog posts on the Internet, including:
- The rise of celebrities as "medical experts" and the public health menace they pose
- What should doctors say when patients ask how often they’ve performed a procedure?
- Health care reform: bloggers have all the answers
Join us on our blog for our edition of the oldest and most popular medical blog "carnival" on the Internet.
Cartoon caption contest.
Put words in our mouth
ACP InternistWeekly wants readers to create captions for this cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate good toward any ACP product, program or service.
E-mail all entries by June 18. ACP staff will choose three finalists and post them in the June 23 issue of ACP InternistWeekly for an online vote by readers. The winner will appear in the June 30 edition of ACP InternistWeekly..
MKSAP Answer and Critique
The correct answer is C) Gleason score. This item is available online to MKSAP subscribers in the Hematology and Oncology section: Item 90.
ACP's Medical Knowledge Self-Assessment Program (MKSAP) allows you to:
- Update your knowledge in all areas of internal medicine
- Prepare for ABIM certification or recertification
- Support your clinical decisions in practice
- Assess your medical knowledge with 1,200 multiple-choice questions
To order the latest edition of MKSAP, go online.
This patient's Gleason score of 8 includes a component of Gleason grade 5 and is predictive of a tumor likely to recur after local therapy. In the Gleason histologic scoring system, tumors are graded from 1 to 5 based on the degree of glandular differentiation and structural architecture. Grade 1 represents the most well-differentiated tumors, and grade 5 represents the most poorly differentiated tumors. A primary and secondary score are reported and combined to form the combined Gleason score. The composite Gleason score is derived by adding together the two most prevalent differentiation patterns (a primary and a secondary grade). In approximately 20% of cases, the Gleason score is upgraded during surgery. Total Gleason scores of 2 to 4 represent well-differentiated tumors, 5 to 6 represent moderately differentiated tumors, 7 represents moderately poorly differentiated tumors, and 8 to 10 represent poorly differentiated tumors. There is a growing belief that the first (and thus most prevalent) of the two reported Gleason grades may be the most predictive of outcome; consequently, a Gleason score of 7 (4 + 3) may be a more aggressive tumor than one with a Gleason score of 7 (3 + 4).
No randomized trials currently exist comparing surgery to radiation therapy in this population. In matched case–control studies, outcomes in patients after surgery and radiation therapy appear equal at 7 years; therefore, choice of therapy does not have an impact on this patient's outcome. Most patients do not have a family history of prostate cancer, and the lack of a family history does not have a clear impact on outcome. This patient's asymptomatic status at diagnosis does not impact the prognosis because most patients do not have symptoms at diagnosis.
- In the Gleason histologic scoring system, grade 1 represents the most well-differentiated tumors, and grade 5 represents the most poorly differentiated tumors.
- Gleason scores consist of two scores derived from the most prevalent and second most prevalent differentiated tumors, which results in a combined score.
- The first of the two reported Gleason scores in the combined score may be most predictive of outcome.
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