In the News
for the Week of 9-21-10
- Glucosamine, chondroitin not effective for hip or knee osteoarthritis
- Low-dose aspirin may protect against colorectal cancer
- MKSAP Quiz: ulcerative colitis
- Evidence lacking for routine prostate screening, but single test at 60 may help
- Exacerbation-susceptible subtype may exist in COPD
- Metabolic syndrome predicts death, cardio disease
- Correctional health care conference to be held in October
From the College
- ACP responds to Pakistan flooding tragedy
- ACP's John Tooker, MACP, blogs at KevinMD
- Candidates announced for Board of Governors Chair-elect
Cartoon caption contest
- Put words in our mouth
Physician editor: Darren Taichman, FACP
Glucosamine, chondroitin not effective for hip or knee osteoarthritis
The popular supplements glucosamine and chondroitin have no effect on pain or joint space narrowing in hip and knee osteoarthritis, according to a new study.
Researchers in the United Kingdom performed a network meta-analysis of 10 trials to determine whether glucosamine, chondroitin or the two combined helped knee or hip pain in osteoarthritis. In the network meta-analysis, the authors wrote, “Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian model that allowed the synthesis of multiple time points.” The main outcome measure was pain intensity, while the secondary outcome was change in joint space narrowing. The researchers defined −0.9 cm on a 10-cm visual analogue scale as a clinically important difference between study preparations and placebo. The results were published online Sept. 16 by BMJ.
The 10 included trials involved 3,803 patients, with an average age of 58 to 66 years. A median of 68% of patients were women. The difference in pain intensity for supplements compared with placebo was −0.4 cm (95% credible interval, −0.7 to −0.1 cm) for glucosamine, −0.3 cm (95% credible interval, −0.7 to 0.0 cm) for chondroitin and −0.5 cm (95% credible interval, −0.9 to 0.0 cm) for the combination. Trials funded by industry showed larger supplement effects than trials that were not industry funded (P=0.02). Joint space narrowing differed only minutely between groups.
The authors noted that the included trials measured joint pain with different instruments, which could have affected their results, among other limitations. However, they concluded that chondroitin and glucosamine, while not harmful, do not benefit patients with knee or hip osteoarthritis. "Coverage of costs by health authorities or health insurers for these preparations and novel prescriptions to patients who have not received other treatments should be discouraged," they wrote..
Low-dose aspirin may protect against colorectal cancer
Aspirin may protect against development of colorectal cancer even at low doses, according to a new study.
Existing evidence indicates that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, can reduce risk for colorectal cancer, but the lowest effective dose, optimal duration, and effect on survival have not yet been determined. Researchers in Scotland performed a population-based case-control study to examine the relationship between colorectal cancer risk and use of NSAIDs. Cases (n=2,279) and controls (n=2,907) matched for age, sex and residential area completed questionnaires that asked about their diet and lifestyles one year before colorectal cancer diagnosis or before study recruitment, respectively. The researchers classified NSAID use as low-dose aspirin (75 mg), non-aspirin NSAIDs and any NSAID. To be considered to have used NSAIDs, cases and controls had to have taken more than four tablets weekly for more than a month. The study results were published online Sept. 15 by Gut.
Mean age was 62.2 years for cases and 62.5 years for controls. Overall, 648 cases (28.4%) and 1,025 controls (35.3%) reported taking any NSAID. Three hundred fifty-four cases (15.5%) and 526 controls (18.1%) reported taking low-dose aspirin. Use of any NSAID conferred a lower risk for colorectal cancer (odds ratio, 0.73; 95% CI, 0.64 to 0.83). For aspirin, larger doses (>525 mg/wk) were associated with the greatest risk reduction (odds ratio, 0.66; 95% CI, 0.41 to 1.05), but low-dose aspirin also had a protective effect (odds ratio, 0.78; 95% CI, 0.65 to 0.92; P=0.001). The inverse association between low-dose aspirin and colorectal cancer increased along with duration of use (P=0.004 for trend). The authors performed a cumulative dose analysis and found that risk reduction with low-dose aspirin could be detected after one year but became statistically significant after five years of consistent use. Larger doses of NSAIDs did not appear to affect all-cause or colorectal cancer-specific survival (hazard ratios, 1.11; 95% CI, 0.94 to 1.33; P=0.22 and 1.01; 95% CI, 0.83 to 1.23; P=0.93, respectively).
The authors acknowledged that they could not tell whether patients kept taking NSAIDs after a cancer diagnosis, which would limit their findings on survival, and that they did not have data on plasma levels of NSAIDs in study participants. However, they concluded that lower doses of aspirin protect against colorectal cancer and that this effect increases over time. They called for randomized, controlled trials of incident colorectal cancer to assess the possible effect of NSAIDs on survival.
MKSAP Quiz: ulcerative colitis
A 27-year-old woman with an 8-year history of ulcerative colitis is evaluated during a follow-up examination. The initial colonoscopy after diagnosis showed pancolitis. She has been treated with mesalamine since diagnosis and has had episodes of bloody diarrhea two or three times a year but has otherwise done well. Her most recent colonoscopy 1 year ago when she had increased diarrhea and bleeding showed no progression of disease. Since then she has been clinically stable. The patient’s medical history includes nephrolithiasis, and her only medications are mesalamine, 2.4 g/d, and a multivitamin. There is no family history of inflammatory bowel disease or colorectal cancer.
On physical examination, vital signs are normal; BMI is 20.5. There is mild abdominal tenderness in the right lower quadrant without rebound or guarding. The rest of the physical examination is normal. Laboratory studies reveal a normal complete blood count, including leukocyte differential, and a serum C-reactive protein level of 0.8 mg/dL (8 mg/L).
Which of the following is the most appropriate management of this patient’s risk for colorectal cancer?
A) Annual capsule endoscopy
B) Annual flexible sigmoidoscopy
C) Colonoscopy now and annually thereafter
D) Increasing the dose of mesalamine to 3.6 g/d
Click here or scroll to the bottom of the page for the answer and critique.
Evidence lacking for routine prostate screening, but single test at 60 may help
An analysis of randomized, controlled trials did not find support for routine population screening for prostate cancer, although a single prostate-specific antigen (PSA) test at age 60 could identify those most likely to develop and die from the disease.
Researchers at the University of Florida reviewed six trials involving 387,286 participants. They found in BMJ that screening helps diagnose prostate cancer at an earlier stage, but does not significantly reduce mortality while risking overtreatment.
Six randomized, controlled trials from January 2005 to July 2010 totaled 387,286 participants. Screening was associated with increased diagnosis of prostate cancer (relative risk [RR], 1.46; 95% CI, 1.21 to 1.77; P<0.001) and stage I prostate cancer (RR, 1.95; 95% CI, 1.22 to 3.13; P=0.005). But there was no significant effect of screening on death from prostate cancer (RR, 0.88; 95% CI, 0.71 to 1.09; P=0.25) or overall mortality (RR, 0.99; 95% CI, 0.97 to 1.01; P=0.44).
All the trials had substantial methodological limitations and none provided data on the effects of screening on quality of life. The authors suggest men should be better informed about the uncertainties associated with screening, "that is, detection of cancer that will not negatively affect survival."
Instead, clinicians should focus attention on screening men at age 60 and finding out who has PSA levels above 2 ng/mL, according to a second study. Researchers in Sweden and at Memorial Sloan Kettering Cancer Center in New York determined that a single PSA test at age 60 strongly predicts a man’s lifetime risk of diagnosis and mortality.
They found in BMJ that 90% of prostate cancer deaths occurred in men who'd had the highest PSA levels at age 60. Men with average or low PSA levels had negligible rates of prostate cancer or death by age 85. Results suggest that at least half of men aged 60 and older might not need prostate cancer screening, which could reduce overdiagnosis and overtreatment.
The researchers conducted a case-control study of 1,167 Swedish men born in 1921 who'd provided blood samples in 1981 and were followed to age 85. The blood samples were of archival anticoagulated plasma. Few men in that time period had undergone PSA screening, avoiding verification bias.
There were 43 cases of metastasis and 35 deaths from prostate cancer. PSA levels at age 60 were associated with prostate cancer metastasis (area under the curve [AUC], 0.86; 95% CI, 0.79 to 0.92; P<0.001) and death from prostate cancer (AUC, 0.90; 95% CI, 0.84 to 0.96; P<0.001).
Although only a minority of the men with PSA concentrations in the top quarter (>2 ng/mL) developed fatal prostate cancer, 90% (78% to 100%) of deaths from prostate cancer occurred in these men. Conversely, men aged 60 with PSA concentrations at the median or lower (<1 ng/mL) were unlikely to have clinically relevant prostate cancer (0.5% risk of metastasis by age 85 and 0.2% risk of death from prostate cancer). Though the latter group might harbor prostate cancer, it is unlikely to become life-threatening, the researchers concluded. Overall, men with PSA levels of 2 ng/mL or greater at age 60 had 26 times (95% CI, 2 to 113 times) the odds of dying from prostate cancer.
An accompanying editorial suggested that younger men at high risk of prostate cancer, such as those with a strong family history and higher baseline PSA concentrations, should be followed closely, while elderly men and those with a low risk of disease could be tested less often, if at all. “Approaches such as these will hopefully make the next 20 years of PSA-based screening better than the first 20,” the editorialist wrote.
Exacerbation-susceptible subtype may exist in COPD
Patients who have chronic obstructive pulmonary disease (COPD) with frequent exacerbations may have a distinct phenotype in moderate and severe disease stages, researchers found.
Researchers reviewed exacerbations in 2,138 patients for three years in a large observational study, the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study. Recruitment criteria included ages 40 to 75, a history of 10 or more pack-years of smoking, forced expiratory volume in 1 second (FEV1) of less than 80% of predicted value after bronchodilator use, and FEV1 to forced vital capacity of 0.7 or less. Patients were measured at baseline, at three and six months, and every six months for three years.
Exacerbations were defined by the patients' primary doctors based on common clinical criteria, such as events that led a clinician to prescribe antibiotics and/or corticosteroids, or that led to hospitalization. Researchers applied Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages. Results appeared in the Sept. 16 New England Journal of Medicine. The study was funded by GlaxoSmithKline.
Exacerbation rates increased as GOLD stage severity did. But the single best predictor of exacerbations across all GOLD stages was an exacerbation treated in the previous year (odds ratio, 4.3; 95% CI, 3.58 to 5.17; P<0.001). Among 945 patients with moderate COPD, 208 (22%) had two or more during the first year of the study. Among the 293 patients in the study with severe COPD, 138 (47%) had two or more exacerbations during the first year of the study, and 84 (29%) had no exacerbations.
Severe COPD patients free of exacerbations one year prior to study entry were less likely to have them during the three-year study period (odds ratio, 4.53; 95% CI, 2.62 to 7.82; P<0.001). No other variables were significantly associated with exacerbations.
The study author wrote that if the exacerbation-susceptibility phenotype exists, it may represent an intrinsic susceptibility or exposure to triggers such as respiratory viral infections. Identifying this phenotype may help doctors better target patients for interventions.
Metabolic syndrome predicts death, cardio disease
Metabolic syndrome is a significant predictor of cardiovascular outcomes and all-cause mortality, according to a new systematic review and meta-analysis.
The analysis included 87 studies (with more than 900,000 patients) that assessed the relationship between metabolic syndrome and cardiovascular outcomes. Most of the studies used the 2001 National Cholesterol Education Program (NCEP) definition of metabolic syndrome, which requires three or more of five cardiovascular risk factors: central obesity, elevated triglycerides, diminished HDL cholesterol, systemic hypertension and elevated fasting glucose. The other studies used the 2004 revised (rNCEP) definition, which differs mainly in that the threshold for fasting glucose was lowered from 110 to 100 mg/dL.
After the definitions and the studies were pooled, the analysis found that metabolic syndrome was associated with a more than doubled risk of cardiovascular disease and stroke, and a 1.5-fold increase in the risk of all-cause mortality. The researchers also looked at whether this increased risk could be explained by patients with metabolic syndrome having a high rate of type 2 diabetes. They found this not to be true; even in patients without type 2 diabetes, metabolic syndrome was associated with a 62% increased risk of myocardial infarction and 86% increased risk for stroke.
There is still a need for prospective research to determine whether metabolic syndrome identifies a risk independent of that of its individual components, the study authors said. Despite that uncertainty, they recommended that health care workers use metabolic syndrome as a diagnostic tool for identifying at-risk patients.
The use of the NCEP versus the rNCEP definition of metabolic syndrome makes little difference in identifying risk, the authors noted, and they suggested that the definition of metabolic syndrome should not require type 2 diabetes as a component, because nondiabetic patients also face significantly increased risks. The analysis was published in the Sept. 20 Journal of the American College of Cardiology.
Correctional health care conference to be held in October
The National Commission on Correctional Health Care will hold its national conference Oct. 9-13, 2010 in Las Vegas.
The National Conference on Correctional Health Care is designed to help correctional health professionals improve care quality and achieve professional advancement. Preconference seminars will focus on fundamentals in correctional health care, while concurrent sessions will feature presentations on medical care, mental health care, legal issues and cost containment, among other topics. ACP is a supporting organization of the National Commission on Correctional Health Care. More information about the conference is available online.
From the College.
ACP responds to Pakistan flooding tragedy
ACP is deeply saddened by the terrible flooding in Pakistan and is encouraging all College membersthe internal medicine community in the United States and other countriesto consider donating to one or more charitable organizations that will directly benefit those affected by this disaster. A list of reputable charities is posted online.
On Aug. 31, the College sent an e-mail to all ACP members in Pakistan to express sympathy about the recent flooding there. The e-mail offered dues waivers for members affected by the flooding as well as free access to PIER for their non-member colleagues. The College has received many responses from members in Pakistan, one of which eloquently captures the dire situation..
ACP's John Tooker, MACP, blogs at KevinMD
John Tooker, MACP, ACP's associate executive vice president, begins his monthly column at KevinMD.com, one of the Web's most influential medical blogs. This month's column is titled "Primary Care Education and TrainingTime for Change?".
Candidates announced for Board of Governors Chair-elect
Michael C. Sha, FACP, and Thomas G. Tape, FACP, are seeking election as Chair-elect of the Board of Governors. The College’s Governors have been casting ballots online, with the winner to be announced October 2010. The winner will begin his term at the conclusion of Internal Medicine 2011 and take office as Chair in April 2012.
Dr. Sha received his medical degree from the Indiana University School of Medicine, where he also completed his residency and fellowship training. He is board certified by the American Board of Internal Medicine, with added qualifications in geriatric medicine. He is an assistant professor of clinical medicine at the Indiana University School of Medicine. Dr. Sha received his ACP Fellowship in 2006. He became Governor of the Indiana Chapter in 2008 and is a member of the Chapter Subcommittee and the Ethics, Professionalism and Human Rights Committee. He chaired the Council of Young Physicians and Council of Associates and has served two ex-officio terms on the Board of Regents. Dr. Sha is also a member of the Board of Trustees for the Indiana State Medical Association.
Dr. Tape received his medical degree from the Washington University Medical School in St. Louis, Mo. He completed his residency and general internal medicine at the Strong Memorial Hospital, University of Rochester. Dr. Tape is board certified by the American Board of Internal Medicine. Presently, he is a professor of medicine, chief, Section of General Internal Medicine, and vice chair for clinical affairs, Department of Internal Medicine at the University of Nebraska College of Medicine. Dr. Tape is also an attending physician at the Nebraska Medical Center and the Omaha Veterans Affairs Medical Center, Omaha, Neb. He received his ACP Fellowship in 1991. He became Governor of the Nebraska Chapter in 2008. He is the vice chair of the Medical Service Committee.
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 to email@example.com. ACP staff will choose finalists and post them online for an online vote by readers. The winner will appear in an upcoming edition..
MKSAP answer and critique
The correct answer is C) Colonoscopy now and annually thereafter. This item is available to MKSAP 15 subscribers as item 4 in the Gastroenterology and Hepatology module.
This patient has pancolitis of 8 years’ duration. The inflammation involves the ileum and proximal colon. The colon cancer risk in patients with ulcerative colitis or Crohn disease reaches a significant level after 8 years of inflammation; the annual cancer risk is estimated to be 1% to 2% per year after 8 years. The cancer risk is slightly delayed for patients with inflammation limited to the distal colon. The recommendation is to initiate a surveillance program with colonoscopy 8 years after onset of her disease, with follow-up colonoscopy every 1 to 2 years thereafter. Biopsies are performed in four-quadrant fashion throughout the entire colon.
The patient’s disease is reasonably well controlled on her current dose of mesalamine, and treatment with mesalamine does not in itself prevent colon cancer. There is no recommendation for standard screening for small-bowel carcinoma in the setting of ulcerative colitis or Crohn disease, and therefore, capsule endoscopy is not indicated. Flexible sigmoidoscopy would not reach the at-risk colonic mucosa in the proximal colon beyond the reach of the sigmoidoscope.
- Patients with inflammatory bowel disease should initiate screening for colorectal cancer after 8 years of duration of disease.
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Copyright 2010 by the American College of Physicians.
A 30-year-old woman is evaluated for difficult-to-treat migraine. She has had severe headaches, usually on the first day of menses, since menarche. The pain is hemicranial, pulsatile, and associated with severe nausea and vomiting but no aura. She frequently awakens with the attack already in progress. A series of drug regimens have become ineffective in controlling pain. Following physical and neurological exams, what is the most appropriate next step in treatment?
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