How to Improve Office-based Colon Cancer Screening?
Source: Nadel MR, et al. Fecal occult blood testing beliefs and practices of U.S. primary care physicians: Serious deviations from evidence-based recommendations. J Gen Intern Med 2010;25:833-839.
Colon cancer screening (ccs), when properly done, has been shown to improve outcomes. Unfortunately, available screening methods suffer from underutilization, misinterpretation, and inappropriate follow-up.
Nadel et al compared data obtained from the National Survey of Primary Care Physicians' Recommendations and Practices for Cancer Screening during two time intervals (1999-2000 and 2006-2007), compiling responses from PCPs (n = 1134).
Before exploring the results, it is important to note recommendations about CCS. First, in-office screening of samples obtained through digital rectal examination (DRE) is not a recommended strategy; a single, in-office fecal occult blood testing subsequent to DRE will miss 95% of advanced neoplasia. Rather, annual CCS by means of three separate stool samples collected at home is appropriate: ACS guidelines suggest annual screening by three out-of-office samples tested with high-sensitivity guaiac or FIT.
One-fourth of primary care physicians reported using a single in-office sample in 2006-2007, down from one-third in 1999-2000. Low-sensitivity guaiac utilization decreased in the same interval from 77.4% to 61.1%.
Extended-release Carvedilol + Lisinopril in Hypertension
Source: Bakris GL, et al. Effect of combining extended-release carvedilol and lisinopril in hypertension. J Clin Hypertens 2010;12:678-686.
Since the publication of the allhat trial, clinicians have progressively relied upon diuretic-based regimens to manage hypertension (HTN). On the other hand, in the ALLHAT trial, overall mortality was similar with diuretic, calcium channel blocker, or ACE inhibitor, lending credence to the idea that any of the treatment choices is reasonable, at least for the endpoint of all-cause mortality. There was no beta blocker arm in the ALLHAT trial; instead, beta blockers were used as add-on treatment.
Ultimately, only a small minority (about 25%) of patients with HTN are able to be controlled with monotherapy. Hence, clinicians must feel comfortable taking best advantage of available combinations of treatment. The COSMOS Study (Coreg and Lisinopril Combination Therapy in Hypertensive Subjects) randomized 656 hypertensive patients to treatment with extended-release carvedilol, lisinopril (LIS), or both. Each agent, as monotherapy or in combination, was used in the full range of therapeutic doses (e.g., LIS 10 mg, 20 mg, and 40 mg).
Although perhaps counter-intuitive, it was only when the highest doses of combination therapy were compared with highest-dose monotherapy that an advantageous differential of diastolic BP lowering was seen. This is the first clinical trial to combine these specific agents, and the fact that simultaneous initiation of both medications was very well tolerated is reassuring.
Aspirin Resistance and Established Hypertension
Source: Ozben B, et al. Aspirin resistance in hypertensive adults. J Clin Hypertens 2010;12:714-720.
The prophylactic use of aspirin (asa) provides risk reduction when used for secondary prophylaxis. Nonetheless, the protective effects of ASA are imperfect, which is to some degree explained by the concept of ASA resistance, variously measured by failure of aspirin to reduce thromboxane production, platelet activation, or platelet aggregation. Because various methodologies have been used to measure antithrombotic activity of ASA (such as platelet aggregability or thromboxane), the prevalence of ASA resistance in the literature is widely variant. ASA resistance has not been the subject of much study, specifically in hypertensive patients.
Ozben et al used a device called the Ultegra Rapid Platelet Function Assay-ASA to measure the degree of platelet aggregation reduction attained in persons with established hypertension receiving 100-300 mg/d of ASA. The Ultegra device measures light transmission in whole blood to which a platelet activator has been added: If ASA is doing its job, platelets will not activate. If ASA is not doing its job, fibrinogen will agglutinate with platelets, obscuring light transmission. Patients who were taking any other agents that might influence platelet aggregation were excluded from the trial (e.g., clopidogrel).
In the 200 study subjects, ASA resistance was found in 21%. ASA resistance was more common in uncontrolled hypertension, women, chronic kidney disease, and persons with lower platelet counts. Measurement of ASA resistance is not yet a readily applied clinical tool. Whether persons with ASA resistance merit higher doses of ASA, alternative pharmacotherapy (e.g., clopidogrel), or other intervention is unclear.
Dementia and Aggressive Behavior
Source: Kunik ME, et al. Causes of aggressive behavior in patients with dementia. J Clin Psych 2010;71:1145-1152.
Metrics designed to measure aggression in dementia patients list activities such as spitting, verbal aggression, hitting, kicking, pushing, biting, and making inappropriate sexual advances either verbally or physically. Because such behaviors can be highly disruptive, it would be helpful to shed light on factors associated with aggressive behavior.
To be included in the trial, subjects had to be free of a history of aggressive behaviors for the previous 12 months. Factors that were measured included depression (Hamilton Depression Scale), pain, caregiver burden (based upon a validated scoring system that measures psychological, physical, emotional, financial, and social impact of being a caregiver), and an item titled "mutuality," which measures the positive qualities of the caregiver-to-care-receiver relationship, including frequency of contact, positive interactions, degree of attachment, and emotional support. The authors looked at data from 215 patients with dementia, of whom 41% developed aggression over a 2-year interval.
Predictors of increased risk for aggression were low baseline mutuality, high caregiver burden, pain, and depression. Although some of the predictors for aggression may be difficult or impossible to modify, others are clearly modifiable and might reduce likelihood for aggression.
Dabigatran vs Warfarin for AFib
Source: Wallentin L, et al. Efficacy and safety of dabigatran compared with war-farin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation. Lancet 2010;376:975-983.
Warfarin (war) does an impressive job of stroke reduction in patients with atrial fibrillation (AFib): Clinical trials indicate a relative risk reduction of 65%. Unfortunately, chronic WAR therapy is not without obstacles, including need for ongoing monitoring, expense, vigilance to diet and pharmacotherapy, etc. Dabigatran is an orally administered direct thrombin inhibitor that does not require routine monitoring, and is not significantly affected by vitamin K content in food. In October 2010, the FDA approved dabigatran for reduction of risk of stroke in persons with AFib.
The RE-LY trial randomized AFib patients (n = 18,113) to anticoagulation with warfarin (target INR, 2.0-3.0) or dabigatran. Dabigatran was administered as either 110 mg bid or 150 mg bid. Patients were followed for 2 years.
Initial reporting of RE-LY results found that lower-dose dabigatran (110 mg bid) was non-inferior to warfarin, and that higher-dose dabigatran (150 mg bid) was superior to warfarin. This article further examined whether trial results were impacted by the degree of success with which study sites were able to keep patients within the therapeutic range with warfarin.
Ultimately, the efficacy of dabigatran 150 mg bid relative to WAR for stroke prevention was found not to be dependent upon the efficacy with which clinical trial centers maintained INR within the therapeutic range. On the other hand, for the endpoints of all vascular events, non-hemorrhagic events, and mortality, differences between dabigatran and WAR were greater at study sites with less efficacy at maintaining in-range INR. Dabigatran appears to be at least as effective as WAR, although some advantages of dabigatran are magnified by inconsistencies in maintaining good INR control.
When Should a Non-diabetic A1c Be Rechecked?
Source: Takahashi O, et al. A1c to detect diabetes in healthy adults: When should we recheck? Diabetes Care 2010;33:2016-2017.
Recently, the ada has advocated the use of A1c to diagnose diabetes, indicating that we may now make a diagnosis of diabetes with an A1c ≥ 6.5. We do not have explicit guidance about the frequency with which persons whose A1c falls below the diagnostic threshold should be rechecked.
Takahashi et al followed all adults participating in preventive health check-ups (n = 16,313) at the Center for Preventive Medicine at St. Luke's International Hospital, Tokyo, from 2005 to 2008. Three years after enrollment, among those without diabetes at baseline, 3.2% had reached an A1c ≥ 6.5. However, the likelihood of progressing to diabetes varied widely and was dependent upon the baseline non-diabetic A1c: Only 0.05% of persons with an A1c < 5% became diabetic vs 20% of those with an A1c 6.0%-6.4% at baseline.
Based upon their observations, the authors suggest that if baseline A1c is < 6.0%, rescreening is unlikely to be valuable in less than 3 years. On the other hand, the high frequency of A1c progression when baseline A1c is 6.0%-6.4% merits consideration of annual rescreening.
How to Improve Office-based Colon Cancer Screening?; Extended-release Carvedilol + Lisinopril in Hypertension; Aspirin Resistance and Established Hypertension; Dementia and Aggressive Behavior; Dabigatran vs Warfarin for AFib; When Should a Non-diabetic A1c Be Rechecked?You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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