SCREENING FOR PROSTATE CANCER
Screening for prostate cancer is done commonly in clinical practice, using prostate-specific antigen (PSA) tests or digital rectal examination (DRE). Evidence is lacking, however, to confirm a survival benefit among screened patients. The authors of this study evaluated the effectiveness of PSA, with or without DRE, in reducing mortality. A multicenter nested case-control study was conducted at 10 Veterans Affairs medical centers in New England. Among 71,661 patients receiving ambulatory care between 1989 and 1990, 501 case patients were identified as men who were diagnosed as having adenocarcinoma of the prostate from 1991 through 1995, and who died sometime between 1991 and 1999. Control patients were men who were alive at the time the corresponding case patient had died, matched (1:1 ratio) for age and Veterans Affairs facility. The exposure variable (determined blind to case-control status) was whether PSA testing or DRE was performed for screening prior to the diagnosis of prostate cancer among case patients, with the same time interval for control patients. The association of screening and overall or cause-specific (prostate cancer) mortality was adjusted for race and comorbidity. The resultsÊshowed a benefit of screening was not found in the primary analysis assessing PSA screening and all-cause mortality (adjusted odds ratio, 1.08; 95% confidence interval, 0.71-1.64; PÊ=Ê.72), nor in a secondary analysis of PSA and/or DRE screening and cause-specific mortality (adjusted odds ratio, 1.13; 95% confidence interval, 0.63-2.06; PÊ=Ê.68). The authors concluded that these results do not suggest that screening with PSA or DRE is effective in reducing mortality. Recommendations for obtaining “verbal informed consent” from men regarding such screening should continue.

Concato J, Wells CK, Horwitz RI,, et al. The effectiveness of screening for prostate cancer. Arch Intern Med 2006;166:38-43



MANAGEMENT OF ATHEROTHROMBOSIS WITH CLOPIDOGREL
The secondary prevention of ischemic stroke is aided by the use of antiplatelet therapy, and the predominant current choices are aspirin, aspirin plus extended-release dipyridamole, and clopidogrel. The potential utility of combining platelet antiaggregants with different mechanisms of action proved successful with aspirin plus extended-release dipyridamole, and this approach has been explored with the combination of clopidogrel and aspirin. In the Management of Athero-thrombosis With Clopidogrel in High-Risk Patients trial, this combination was compared with clopidogrel alone for secondary prevention in patients with transient ischemic attack and stroke in a high-risk population with a high prevalence of other vascular risk factors. A nonsignificant trend for a reduction of the combined endpoint of ischemic stroke, myocardial infarction, vascular death, and rehospitalization was observed in the combination therapy group (PÊ=Ê.24). The frequency of serious, life-threatening bleeding adverse effects was almost doubled in the combination arm. Neurologists need to be aware of these results and avoid the use of clopidogrel plus aspirin in patients with stroke or transient ischemic attack until evidence that the combination is safe in this population is provided. Neurologists faced with patients who have had a stroke or transient ischemic attack and are receiving this combination of antiplatelet agents after coronary stenting should inform their cardiology colleagues of the reported bleeding risk, and they should encourage the use of the combination for as short a time period as possible after such coronary intervention.

Fisher M. Results of the Management of Atherothrombosis with Clopidogrel in High-Risk Patients trial. Arch Neurol 2006;63:20-24.



MEMANTINE IN MODERATE-TO-SEVERE ALZHEIMER’S DISEASE
This study was an extension of a 28-week, randomized, double-blind, placebo-controlled study of memantine in 252 patients with moderate-to-severe Alzheimer disease. Raters remained blind to the patients’ initial study treatment. Patients (nÊ=Ê175) were enrolled from the previous double-blind study in an outpatient setting. Dosage of memantine was 20 mg daily. Efficacy assessments from the double-blind study were continued and safety parameters were monitored. Results showed that patients who switched to memantine treatment from their previous placebo therapy experienced a significant benefit in all main efficacy assessments (functional, global, and cognitive) relative to their mean rate of decline with placebo treatment during the double-blind period (P < .05). The completion rate for the extension phase of the study was high (78%), and the favorable adverse-event profile for memantine therapy was similar to that seen in the double-blind study. The authors concluded that these results extend previous findings that demonstrated the efficacy and safety of memantine in the treatment of patients with moderate-to-severe Alzheimer disease.

Reisberg B, Doody R, Stöffler A, et al. A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease. Arch Neurol 2006;63:49-54.



ANTIMICROBIAL URINARY CATHETERS TO PREVENT CATHETER-ASSOCIATED UTI
The efficacy of antimicrobial urinary catheters in hospitalized patients is poorly defined.

This systematic review sought to assess currently marketed antimicrobial urinary catheters for preventing catheter-associated urinary tract infection (UTI). Sources used were electronic databases, conference proceedings, bibliographies, trialists, and catheter manufacturers (search dates, 1966 to June 2005). The investigators conducted randomized and quasi-randomized trials of nitrofurazone-coated or silver alloy–coated antimicrobial urinary catheter use for less than 30 days, with no language restriction. Study design, study sample, inclusion and exclusion criteria, allocation, blinding, UTI definition, ascertainment methods, and proportion developing symptomatic UTI (primary end point) or bacteriuria (secondary end point) were extracted by using a structured data collection instrument. Twelve qualifying trials (13, 392 total participants or catheters) were identified. They compared nitrofurazone-coated silicone (n = 3) or silver-coated latex (n = 9) catheters with silicone or latex catheters. No study addressed symptomatic UTI. All trials suggested protection against bacteriuria with test catheter use. However, effect size varied considerably and postrandomization exclusions were very common. Effect size was greatest in trials of nitrofurazone-coated catheters (all post-1995) and in pre-1995 silver alloy–coated catheter trials and was smallest in post-1995 silver alloy–coated catheter trials. Control group bacteriuria rate, control catheter type (latex vs. silicone), and patient sample (urology vs. other) also predicted effect size. Few studies addressed secondary bloodstream infection, mortality, costs, or microbial resistance. Short-term adverse effects were minimal. The study was limited by the number, size, and quality of studies and by lack of the following: intention-to-treat analyses, data on clinical end points, and trials comparing nitrofurazone-coated with silver alloy–coated catheters.
Conclusions: According to fair-quality evidence, antimicrobial urinary catheters can prevent bacteriuria in hospitalized patients during short-term catheterization, depending on antimicrobial coating and several other variables. Older data probably lack current relevance. Cost implications and effect on infectious complications remain undefined.

Johnson JR, Kuskowski MA, Wilt TJ. Systematic review: Antimicrobial urinary catheters to prevent catheter-associated urinary tract infection in hospitalized patients. Ann Intern Med 2006; 144(2):116-126.



EXERCISE AND REDUCED RISK OF INCIDENT DEMENTIA
Alzheimer’s disease and other dementing disorders are major sources of morbidity and mortality in aging societies. Proven strategies to delay onset or reduce risk for dementing disorders would be greatly beneficial. The objective of this study was to determine whether regular exercise is associated with a reduced risk for dementia and Alzheimer’s disease. A prospective cohort study was conducted at Group Health Cooperative, Seattle, Washington, with 1740 persons older than age 65 years without cognitive impairment who scored above the 25th percentile on the Cognitive Ability Screening Instrument (CASI) in the Adult Changes in Thought study, and who were followed biennially to identify incident dementia. Baseline measurements included exercise frequency, cognitive function, physical function, depression, health conditions, lifestyle characteristics, and other potential risk factors for dementia (for example, apolipoprotein E 4). Results showed that during a mean follow-up of 6.2 years (SD, 2.0), 158 participants developed dementia (107 developed Alzheimer’s disease). The incidence rate of dementia was 13.0 per 1000 person-years for participants who exercised 3 or more times per week compared with 19.7 per 1000 person-years for those who exercised fewer than 3 times per week. The age- and sex-adjusted hazard ratio of dementia was 0.62 (95% CI, 0.44 to 0.86; P = 0.004). The interaction between exercise and performance-based physical function was statistically significant (P = 0.013). The risk reduction associated with exercise was greater in those with lower performance levels. Similar results were observed in analyses restricted to participants with incident Alzheimer disease. Limitations were that exercise was measured by self-reported frequency, and the study population had a relatively high proportion of regular exercisers at baseline. The authors concluded that these results suggest that regular exercise is associated with a delay in onset of dementia and Alzheimer’s disease, further supporting its value for elderly persons.

Larson EB, Wang L, Bowen JD, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med 2006;144 (2):73-81.