In the News
for the Week of 8-3-10
- Calcium supplements may increase cardiovascular risk
- Industry trial registrations indicate positive publication bias
- MKSAP Quiz: treating rectal cancer
- Updated guidelines issued on management of spontaneous intracerebral hemorrhage
- Insurance company’s anti-antacid project had little effect
- Physicians avoid e-prescribing even if they have access
- Low-risk, low-PSA prostate cancer receiving aggressive interventions
From the College
- Call for spring 2011 Board of Governors resolutions
- Expert panel: physicians need to practice better lifestyle medicine
- Last chance to register for Webinar on EHR meaningful use
Cartoon caption contest
- And the winner is …
Physician editor: Darren Taichman, FACP
Calcium supplements may increase cardiovascular risk
Calcium supplements may increase risk for cardiovascular events in patients with or at risk for osteoporosis, a new study reports.
Researchers performed a meta-analysis of randomized, placebo-controlled trials that looked at use of calcium supplements of at least 500 mg/d in patients older than age 40. Trials that examined calcium supplementation plus vitamin D were excluded. Primary end points were time to first myocardial infarction (MI), first stroke, and first composite end point event (MI, stroke or sudden death). All-cause mortality was the secondary end point. The study was published online July 29 by BMJ.
Fifteen trials involving more than 12,000 patients were included in the study. Of these trials, five had patient-level data and 11 had trial-level data. In the patient-level data, the hazard ratio for MI was 1.31 (95% CI, 1.02 to 1.67; P=0.035) for patients who took calcium versus those who took placebo, and incidence of stroke, the composite end point, and all-cause mortality saw nonsignificant increases in this group. In the trial-level data, the pooled relative risk for MI associated with calcium supplementation was 1.27 (95% CI, 1.01 to 1.59; P=0.038).
The authors noted that their results cannot be generalized to include calcium supplementation plus vitamin D and that the included trials did not use cardiovascular outcomes as primary end points. However, they concluded that calcium supplements are associated with an increased MI risk that could translate to a substantial disease burden, given their widespread use. The role of calcium supplements in osteoporosis management should be reassessed, the authors said.
An accompanying editorial noted that since the benefits of calcium supplements are not definitively proven, any risk associated with their use is not warranted. "On the basis of the limited evidence available, patients with osteoporosis should generally not be treated with calcium supplements, either alone or combined with vitamin D, unless they are also receiving an effective treatment for osteoporosis for a recognized indication," the editorialists concluded..
Industry trial registrations indicate positive publication bias
Clinical trials that are funded by industry are much more likely to publish positive results about the drugs they study than trials funded primarily by the government or other sources, according to a new analysis.
Researchers used the Web-based registry ClinicalTrials.gov to collect information about safety and efficacy trials of anticholesteremics, antidepressants, antipsychotics, proton-pump inhibitors and vasodilators conducted between 2000 and 2006. The analysis included 546 drug trials, 63% of which were primarily funded by industry, compared to 14% by the government and 23% by nonprofit or nonfederal organizations. Overall, the researchers were able to find published results for 66% of the registered trials. The study was published in the Aug. 3 Annals of Internal Medicine.
Of the industry-funded trials that were published, 85% showed positive outcomes, compared to 50% of government trials and 72% of the nonprofit/nonfederal group. Some of the nonprofit/nonfederal trials used contributions from industry, and those that did so were significantly more likely to report positive outcomes than those that didn’t get money from industry. Industry-funded trials were also less likely to be published within two years of completion than the other types—only 32% compared to 56% of the nonfederal/nonprofit trials.
Noting that industry trials are more likely to be in phase 3 or 4, and therefore potentially more likely to be positive than early-stage research, the researchers controlled for trial phase and still found an association between industry funding and positive outcomes. The study authors also noted that many trials were not registered until after the study got under way or, in some cases, was published. Many registrations also failed to link to resulting publications, making it more difficult to track the results of trials.
The study authors concluded that more accurate, timely and expanded reporting in trial registrations is needed to maximize the transparency of the clinical trial process. They also listed some potential changes to ClinicalTrials.gov, including incorporating study protocols and amendments into registrations and making the information from FDA drug reviews public.
MKSAP Quiz: treating rectal cancer
A 56-year-old woman undergoes initial screening colonoscopy. An abnormality is found 10 cm from the anal verge. Biopsy specimens confirm the diagnosis of a moderately differentiated adenocarcinoma. Rectal ultrasonography shows that the tumor has extended into the perirectal fat, but no lymphadenopathy is noted. Chest radiograph and CT scan of the abdomen and pelvis show no metastatic disease.
Which of the following is the most appropriate treatment at this time?
A) Surgical resection and adjuvant chemoradiation therapy
B) Chemotherapy alone
C) Radiation therapy alone
D) Surgical resection alone
E) Surgical resection and postoperative radiation therapy alone
Click here or scroll to the bottom of the page for the answer and critique.
Updated guidelines issued on management of spontaneous intracerebral hemorrhage
The American Heart Association and American Stroke Association recently issued updated guidelines on management of spontaneous intracerebral hemorrhage (ICH).
Outcomes of spontaneous cerebral hemorrhage can be greatly improved with timely, appropriate medical treatment. The AHA and ASA issued these guidelines in part to stress to clinicians the importance of their role and to provide "an evidence-based framework" for care. New recommendations or those revised from the 2007 guidelines include the following:
- Patients with a severe coagulation factor deficiency or severe thrombocytopenia should receive appropriate factor replacement therapy or platelets, respectively.
- Patients with ICH whose international normalized ratios are elevated due to oral anticoagulants should have warfarin withheld, receive therapy to replace vitamin K-dependent factors and correct the international normalized ratio, and receive intravenous vitamin K.
- Noting incomplete efficacy data pending ongoing trials, recommendations for the control of blood pressure continue to be made according to the systolic and diastolic blood pressure measurements as well as whether there is evidence of increased intracerebral pressure. Clinicians should consult the table provided in the guideline for guidance. In patients presenting with a systolic blood pressure of 150 to 220 mm Hg, acute lowering of systolic blood pressure to 140 mm Hg is probably safe.
- When stratifying a patient’s risk of recurrent ICH may affect other management decisions, it is reasonable to consider the following risk factors: lobar location of the initial ICH, older age, ongoing anticoagulation, presence of the apolipoprotein E ε2 or ε4 alleles and greater number of microbleeds on MRI.
- After the acute ICH, in patients without medical contraindications, blood pressure should be well controlled, especially in those whose ICH location, such as the basal ganglia, thalamus, or brainstem, is typical of hypertensive vasculopathy.
The complete guidelines were published online July 22 by Stroke.
Insurance company’s anti-antacid project had little effect
An insurance company’s effort to encourage physicians to reduce use of acid-suppressive medications did not change prescription rates, a Dutch study found.
The health insurance company initiated a multi-faceted intervention in the central region of the Netherlands. Primary care physicians in the intervention group received a prescription-optimization protocol, a list of their patients who took acid-suppressive drugs (ASDs) on a long-term basis, and financial compensation for additional consultations with these patients. After six months of follow-up, the use of ASDs and the cost and volume of prescriptions were compared between these physicians’ patients and the patients of a control group of physicians who did not receive the intervention. The total study included 112 physicians and data on more than 20,000 patients.
At the start of the study, 2.4% of patients in the practices used ASDs frequently (defined as more than 180 daily doses per year). During the six-month intervention, 14.1% of the patients in the intervention group reduced their use of the drugs. However, an almost identical percentage, 13.7%, of control group participants also reduced their consumption. The groups also had similar changes in the number of prescriptions per patient. The results were published in the July 26 Archives of Internal Medicine.
The study authors offered a number of possible explanations for the apparent failure of the intervention. It’s possible that six months was too short a time to accomplish major shifts in prescriptions. Physicians may also have assumed that the project was financially motivated and therefore reacted negatively to an insurance company offering advice about prescribing. The project was also conducted during a time when ASD use was being publicly discussed, so more patients and physicians in the control group may have been reducing their use of the drug than would have been expected.
The continued use of ASDs may also have been due to patient preference, the authors suggested, noting that drug dependency may have made it difficult for physicians to convince patients to quit or cut back on the drug. Future interventions may need to be tailored to convincing patients, as well as physicians, of the benefits of reduced antacid use, the authors concluded..
Physicians avoid e-prescribing even if they have access
Fewer than 10% of all physicians use advanced e-prescribing capabilities such as drug interaction warnings, even when they have access to them.
Even physicians with access to e-prescribing don't use it, and those who use it still eschew advanced features that the federal government is providing financial incentives for, reports the Center for Studying Health System Change (HSC).
Slightly more than two in five physicians reported that they have e-prescribing capabilities, according to results from HSC's 2008 Health Tracking Physician Survey reported in an issue brief. HSC surveyed 4,182 office-based physicians (response rate, 62%).
Of physicians with e-prescribing capabilities, 64.5% routinely used the drug interaction feature, 53.7% routinely transmitted prescriptions to pharmacies and 34.3% routinely used the formulary information feature. While 59.4% reported that all three features were available in their practice, 22.7% used all three routinely. So in 2008, only 9.6% of all office-based physicians routinely used the three advanced e-prescribing features, according to the study.
Medicare started paying bonuses in 2009 for e-prescribing, and in 2011, “meaningful use” regulations will provide further incentives. Then, penalties will kick in for physicians who don't meet federal requirements.
The percentage of e-prescribers more than doubled between 2008 and 2009, and since the implementation of the bonus program, e-prescriptions have risen 181%.
HSC's issue brief reports that the experience is a harbinger of challenges that federal policymakers will face when rolling out meaningful use regulations. E-prescribing is mature technology, but barriers in other sectors hamstring its rollout. These include formulary information that is seen as incomplete and inaccurate, alert fatigue induced by some systems, and retail and mail-order pharmacies that don't use e-prescribing.
"The challenges to implementation of EMRs as a whole are substantially more complex than e-prescribing," the authors wrote in the issue brief. "And, EMR technology is much less mature, suggesting that policy makers should expect a substantially longer time horizon to achieve meaningful use of health IT than the five- to six-year horizon of the Medicare and Medicaid incentive programs."
Low-risk, low-PSA prostate cancer receiving aggressive interventions
Men diagnosed with prostate cancer with a prostate-specific antigen (PSA) threshold below 4.0 ng/mL had low-risk disease but underwent aggressive interventions anyway, researchers found.
Researchers used data from the Surveillance, Epidemiology, and End Results system for 123,934 men with newly diagnosed prostate cancer from 2004 to 2006. Logistic regression quantified the odds ratios (ORs) of men with low- and high-risk disease and the use of radical prostatectomy (RP) or radiation therapy (RT). Results appear in the July 26 Archives of Internal Medicine.
Men were categorized into low-, intermediate- and high-risk groups using the American Joint Committee on Cancer clinical stage, the PSA level and the Gleason score. Low risk was defined as stage <T2a, PSA level <10.0 ng/mL and Gleason score <6. Intermediate risk was defined as stage T2b, PSA level 10.1 to 20.0 ng/mL or Gleason score 7. High risk was defined as stage >T2c, PSA level >20.0 ng/mL or Gleason score >8. Treatment was defined as attempted curative (applying RP or RT) or conservative management (not treated with either).
Men with screen-detected prostate cancer and PSA values <4 ng/mL were 1.49 (95% CI, 1.38 to 1.62) and 1.39 (95% CI, 1.30 to 1.49) times more likely to receive RP and RT, respectively, and were less likely to have high-grade disease than non-screen-detected prostate cancer (OR, 0.67; 95% CI, 0.60 to 0.76).
Radical prostatectomy was performed on 44% of men with PSA values <4.0 ng/mL, 38% of men with PSA values between 4.1 and 10.0 ng/mL, and 24% of men with PSA values between 10.1 and 20.0 ng/mL. Radiation therapy was performed on 33% of men with PSA values of 4.0 ng/mL or lower, 40% of men with PSA values between 4.1 and 10.0 ng/mL, and 41.3% of men with PSA values between 10.0 and 20.0 ng/mL. The percentage of men who did not receive any attempted curative treatment was 27%, 22%, and 36%, respectively, for low-, intermediate-, and high-risk disease.
Lowering the biopsy threshold while still unable to distinguish indolent cancers from aggressive ones might increase the risk of overdiagnosis and overtreatment, the authors concluded. Decreasing the normal value for PSA from 4.0 to 2.5 ng/mL would double (to 6 million) the number of men with abnormal values. Estimates suggest that needle biopsy would diagnose 32% of them with prostate cancer. Based on these study results, 82.5% of these men would receive attempted curative treatment, although 2.4% would have high-grade cancer. But there is no evidence that the 4.0 ng/mL cutoff would result in an excessive number of potentially noncurable cases.
"Many contemporary men receiving treatment for localized prostate cancer are unlikely to benefit from the intervention," the authors wrote. "Furthermore, it has been documented that men who receive any treatment have increased risk of treatment-related adverse effects. Therefore, it is critical that patients be counseled about treatment-associated adverse effects and benefits when they are deciding about therapy."
From the College.
Call for spring 2011 Board of Governors resolutions
The deadline for submitting new resolutions to be heard at the spring 2011 Board of Governors meeting is Monday, Oct. 4, 2010.
Initiating a resolution provides ACP members an opportunity to focus attention at the ACP national level on a particular issue or topic that concerns them. Members must submit resolutions to their governor and/or chapter council. A resolution becomes a resolution of the chapter once the chapter council approves it.
In accordance with the ACP Board of Governors Resolutions Process, resolutions should clearly distinguish the action requested within its resolved clause(s) as either a policy resolve (“Resolved that ACP policy…”), or a directive, which requests action/study on an issue (“Resolved that the Board of Regents…”). If more than one action is proposed, each should have its own resolved clause. Please contact your governor if you have any questions regarding the resolution format.
The Board of Governors votes on new resolutions, which are then presented to the Board of Regents for action. Members can use the Electronic Resolutions System (ERS) to monitor the status of resolutions. Visit your chapter website and link to the ERS under the “Advocacy” heading..
Expert panel: physicians need to practice better lifestyle medicine
A set of competencies, released in the July 14 Journal of the American Medical Association by an expert panel that included representatives from ACP, urges physicians to take responsibility for helping patients make healthy behavior changes to prevent disease and promote health.
The competencies were developed as a way to begin addressing what the panel identifies as a gap in physician practice; according to the group, the majority of physicians are not talking to patients enough about lifestyle choices. Authors point to evidence showing that lifestyle and behavior changes, such as quitting smoking and increasing exercise, are the most effective first line of therapy in the reduction of chronic disease..
Last chance to register for Webinar on EHR meaningful use
On Aug. 4 at 7:00 p.m. ET, ACP and AmericanEHR Partners are holding a free Webinar, "Meaningful Use and Its Implications For Your Practice," featuring David Blumenthal, FACP, national coordinator for health information technology, and Michael Zaroukian, FACP, chief medical information officer for Michigan State University.
Dr. Blumenthal leads the federal government's programs on health information technology adoption, including meaningful use. Learn more and register online.
Cartoon caption contest.
And the winner is …
ACP InternistWeekly has tallied the voting from its latest cartoon contest, where readers are invited to match wits against their peers to provide the most original and amusing caption.
"I told you you'd like our new patient-centered medical home."
This issue's winning cartoon caption was submitted by Russell A. Kaphan, ACP Member. Readers cast 98 ballots online to choose the winning entry. Thanks to all who voted!
The winning entry captured 52% of the votes.
The runners-up were:
"The beer is nice and all, but I still feel sick …I really think I need a shot."
"I've found this product to be the best for producing a urine sample quickly."
MKSAP answer and critique
The correct answer is A) Surgical resection and adjuvant chemoradiation therapy. This item is available to online to MKSAP 15 subscribers as item 77 in the Hematology and Oncology module.
This patient has T3N0M0 stage II rectal cancer and is likely to benefit from a combined-modality approach. Stage II rectal cancer is treated with surgery and adjuvant chemoradiation therapy. Recurrence and death in stage II and III rectal cancer are decreased when radiation therapy is added to the recommended surgical and chemotherapy approaches. Preoperative chemoradiation with low anterior resection is becoming the treatment of choice to reduce the need for permanent colostomy, local recurrences, and long-term toxicity. However, in a randomized study comparing preoperative to postoperative chemoradiation, disease-free survival and overall survival were similar. Possible complications of radiation therapy include proctitis, intestinal obstruction, stricture, and fistula, often occurring long after treatment.
Radiation therapy as an adjunct to surgery for rectal cancer has been shown to reduce local recurrence but has not improved survival. Radiation therapy alone or chemotherapy alone is inadequate treatment of stage II rectal carcinoma.
- Surgery and adjuvant combined chemotherapy and radiation therapy are the standard treatment for patients with stage II and III rectal cancer.
Click here to return to the rest of ACP InternistWeekly.
About ACP InternistWeekly
ACP InternistWeekly is a weekly newsletter produced by the staff of ACP Internist. It is automatically sent to all College members who have an e-mail address on file with ACP.
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Copyright 2010 by the American College of Physicians.
A 38-year-old woman is evaluated during a follow-up visit. She has a history of well-controlled hypertension and type 1 diabetes mellitus. She is at 16 weeks' gestation with her first pregnancy. Prior to conception she was taking lisinopril, which was discontinued in anticipation of the pregnancy, and labetalol was initiated. Other medications are insulin glargine, insulin lispro, and a prenatal vitamin. Following a physical exam and lab studies, what is the most appropriate step in the management of this patient's hypertension? .
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