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Brief evaluation aids diagnosis of dementia

Clinical question Can simple interviews of caregivers coupled with recall testing aid the diagnosis of dementia?

Bottom line The combination of an 8-item test administered to caregivers coupled with a 10-word recall list is very good at ruling out dementia and is relatively good at diagnosing it in elderly patients with cognitive, behavioral, and mood disorders. (Level of evidence = 2b)

Synopsis The authors evaluated 255 consecutive patients accompanied by a caregiver. The patients were referred for evaluation of cognitive, behavioral, and mood disorders. Each dyad answered 8 yes/no questions (AD8*) and a series of additional tests including the Mini Mental Status Exam, 2-word list recall tests (10 and 15 items), trail-making tests, and so forth. A diagnosis of dementia was established using criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The assessments were conducted independently. Finally, the authors used receiver operator curves to see if the AD8 alone or in combination with other tests performed best. Ultimately, 199 patients were given a diagnosis of dementia; 30, no dementia diagnosis; and 26, uncertain diagnosis. A combination of the AD8 and the 10-item word recall list correctly classified more than 91% of patients. A score of 2 or less on the AD8 and fewer than five items remembered gave the best combination of sensitivity (94.1%) and specificity (81.8%). The corresponding likelihood ratio was 5.2 for a positive test and 0.07 for a negative test. In other words, in this population with a high index of suspicion for dementia, the combination of the AD8 and 10-word recall was very good at ruling out dementia and modestly good at ruling it in.

*A copy of the AD8 table with scoring rules may be found at www.alzheimer.wustl.edu/About_Us/pdfs/AD8form2005.pdf. Accessed July 10, 2007.

Galvin JE, Roe CM, Morris JC. Evaluation of cognitive impairment in older adults: combining brief informant and performance measures. Arch Neurol. 2007;64(5):718-724.

As-needed combination works well in patients with mild persistent asthma

Clinical question Do inhaled corticosteroids really have to be taken daily by patients with mild persistent asthma?

Bottom line For patients with mild persistent asthma, symptoms and exacerbations can be controlled just as well using a combination of beclomethasone 250 mcg plus albuterol 100 mcg used as needed instead of daily. This approach reduces the amount of steroids given and may result in better compliance, as well. (Level of evidence = 1b)

Synopsis For years we’ve been telling our patients with mild persistent asthma that they have to take their corticosteroid inhaler every day, not as needed. But is that really true? These researchers identified 510 patients who were given a 4-week course of beclomethasone dipropionate 250 mcg twice a day plus albuterol inhaler to be used as needed. Those with good control while using this regimen were then randomized to 1 of 4 groups: continued beclomethasone 250 mcg twice a day, plus albuterol as needed; beclomethasone 250 mcg plus albuterol 100 mcg twice a day, plus albuterol as needed; albuterol as needed only; and beclomethasone 250 mcg plus albuterol 100 mcg to be used as needed only. Patients received placebo inhalers to maintain masking, and outcomes were assessed by researchers masked to treatment assignment. Of 466 who started the study, 393 completed the 6-month study; dropouts were similar between groups. Half the patients were women and the mean age was 39 years. A variety of physiologic measures of lung function showed that the as-needed combination of steroid and beta agonist was better than albuterol alone and as effective as the traditional combination of daily steroid and as-needed beta agonist. More important, patients using the steroid and beta agonist combination only as needed had fewer exacerbations than the albuterol-only group (0.74 per year vs 1.63 per year; P < .001) and a similar number as the group taking beclomethasone daily with as-needed albuterol. In addition, patients using the combination of steroid and beta agonist as needed used less total steroids than those taking them daily (18 mg vs 78 mg). The percentage of symptom-free days was also similar between the groups who took steroid plus beta agonist as needed and those who took them daily.

Papi A, Canonica GW, Maestrelli P, et al; for the BEST Study Group. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N Engl J Med. 2007;356(20):2040-2052.

Oral antiseptic reduces VAP in ventilated patients

Clinical question Does oral decontamination reduce pneumonia in mechanically ventilated patients?

Bottom line Oral decontamination with antiseptics reduces ventilator-associated pneumonia (VAP). Decontamination with antibiotics, however, did not reduce VAP, and neither approach had an effect on mortality. (Level of evidence = 1a)

Synopsis This meta-analysis evaluated the effect of oral decontamination with topical antibiotics or antiseptics on reducing VAP. A complete literature search was done, and two independent reviewers determined article inclusion. Included trials were appraised on the basis of randomization, allocation concealment, blinding, completeness of follow-up, similarity of groups at baseline, and clarity of inclusion criteria and outcome definitions. Interobserver agreement for study selection was excellent (kappa = 0.84). The authors included 11 randomized trials with 3,242 patients. Randomization was concealed in nine studies, and nine studies were double-blinded. Eight studies included medical or mixed populations; three studies of antiseptic decontamination were conducted on only surgical or trauma patients. A meta-analysis of the four trials that evaluated antibiotic oral decontamination did not show a reduction in VAP. However, pooled results of the seven trials that used antiseptic oral decontamination did show a reduction in VAP (relative risk = 0.56; 95% CI, 0.39-0.81). Combining all 11 trials also showed a reduction in VAP with oral decontamination; however, there was significant heterogeneity for this outcome. Neither approach reduced overall mortality.

Chan EY, Ruest A, Meade MO, Cook DJ. Oral decontamination for prevention of pneumonia in mechanically ventilated adults: systematic review and meta-analysis. BMJ. 2007;334(7599):889.

Quadrivalent HPV vaccine prevents CIN2/3

Clinical question Does a quadrivalent vaccine against human papillomavirus (HPV) reduce the risk of high-grade cervical intraepithelial neoplasia (CIN)?

Bottom line The quadrivalent vaccine against HPV types 6, 11, 16, and 18 significantly reduces the risk of grade 2 or 3 CIN. It is also prevents anogenital warts. (Level of evidence = 1b)

Synopsis In this study, 12,167 nonpregnant women aged 15 to 26 years were randomized to receive placebo or a quadrivalent vaccine active against HPV types 6, 11, 16, and 18. The immunizations were given at enrollment, at 2 months, and at 6 months. The primary outcome was the incidence of newly diagnosed adenocarcinoma in situ, invasive carcinoma of the cervix related to HPV-16 or -18, or CIN2/3 as assessed by a pathologist masked to treatment assignment. All patients had four or fewer lifetime sexual partners, were not pregnant, and never had an abnormal Pap test result. The majority of the women came from Europe (64%) or Latin America (26%). At the start of the study, approximately 10% were positive for HPV-16 and 4% were positive for HPV-18. The authors looked at the results three ways: intent-to-treat, which included all the patients; per protocol, which excluded women who missed a dose or otherwise violated the study protocol; and susceptible per protocol, which also excluded patients with evidence of pre-existing HPV-16 or HPV-18 infection. In the broadest analysis, the vaccine reduced the risk of CIN2/3 or adenocarcinoma in situ by 44%, from 0.8% to 0.5%, over the 3-year study period. If you exclude women with pre-existing HPV-16 or HPV-18 infection, the vaccine was much more effective. The results from the first group tell us what we can initially expect when we start using this vaccine in the real world; the results from the latter, what we may hope to approach some day as HPV-16 and HPV-18 become less common. There was only one case of CIN2/3 or adenocarcinoma in situ in 5,305 women who received the vaccine compared with 42 cases in the 5,260 women who received placebo. Other than mild pain at the injection site there was no difference in adverse events between groups. A related study published in the same issue of the journal (N Engl J Med. 2007;356[19]:1928-1943) found a similar benefit in the prevention of anogenital disease.

FUTURE II Study Group. Quadrivalent vaccine against human papillomavirus to prevent high-grade cervical lesions. N Engl J Med. 2007;356(19):1915-1927.

Aspirin doses higher than 81 mg/d are not beneficial in cardiovascular disease

Clinical question What is the optimal dose of aspirin for secondary prevention of stroke or MI?

Bottom line In this systematic review of 11 studies including more than 41,000 patients, no evidence was found to support aspirin doses above 81 mg for the secondary prevention of stroke or MI. In addition, higher doses of aspirin are likely to increase the risk of major bleeding. (Level of evidence = 1a–)

Synopsis Approximately one third of the US adult population takes aspirin daily for the prevention of cardiovascular disease (CVD); pharmaceutical research suggests that 60% take 81 mg and 35% take 325 mg. These authors conducted a systematic review of the literature to determine the optimal dose of aspirin for the secondary prevention of CVD. The authors searched MEDLINE, EMBASE, and bibliographies to identify 11 studies, eight randomized controlled trials (RCTs) and three observational studies enrolling more than 41,000 patients. Although no attempts were made to locate unpublished data, it is unlikely that enough of such trials exist to change these results. Some of the studies enrolled patients after stroke or transient ischemic attack; the remaining studies enrolled patients after MI. Endpoints included death and major cardiovascular events. None of the 11 studies showed any benefit to aspirin doses above 81 mg/d. Interestingly, two prospective trials actually showed increased rates of death, MI, or stroke in patients taking higher doses of aspirin. The authors also reviewed the literature on adverse effects of aspirin. Three RCTs and one meta-analysis demonstrated an increased risk of bleeding with higher doses of aspirin. One subsequent meta-analysis failed to show any relationship between aspirin dose and GI bleeding. Nevertheless, given the lack of benefit and possible risk of higher doses, this information is likely relevant to point-of-care decision making.

Campbell CL, Smyth S, Montalescot G, Steinhubl SR. Aspirin dose for the prevention of cardiovascular disease: a systematic review. JAMA. 2007;297(18):2018-2024.

Hepatitis C infection increases risk of non-Hodgkin’s lymphoma

Clinical question Does hepatitis C virus (HCV) infection increase the risk of non-Hodgkin’s lymphoma?

Bottom line Chronic HCV infection increases the risk of non-Hodgkin’s lymphoma, as well as other related lymphoproliferative precursors, including Waldenstrom macroglobulinemia and cryoglobulinemia. (Level of evidence = 2b)

Synopsis The investigators conducted a large, population-based retrospective cohort study including 146,394 US veterans infected with HCV. Cases were compared with 572,303 noninfected control patients matched to sex and age. Individuals blinded to HCV status reviewed inpatient and outpatient records and death registries from more than 150 veterans’ hospitals in the United States. Nearly all patients (97%) were male, with a mean age of 52 years. Data from 1989 through 2004 were included. HCV-infected patients were significantly more likely to develop non-Hodgkin’s lymphoma. In addition, a significantly increased risk of Waldenstrom macroglobulinemia and cryoglobulinemia occurred in HCV-infected individuals. Both of these diseases are considered to be related lymphoproliferative precursors to lymphoma. No increased risk of other hematologic malignancies or thyroid cancer was detected.

Giordano TP, Henderson L, Landgren O, et al. Risk of non-Hodgkin lymphoma and lymphoproliferative precursor disease in US veterans with hepatitis C virus. JAMA. 2007;297(18):2010-2017.

Levels of evidence in Bottom line are explained at www.infopoems.com/levels.html.