Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is an advisor for Endo, Kowa, Pricara, and Takeda.

Encouraging News About Lung Cancer Screening Benefits

Source: National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011; 365:395-409.

Screening for lung cancer by means of chest X-ray (CXR) does not reduce mortality, even with the addition of sputum cytology. Because low-dose helical CT (LDCT) detects much smaller, earlier lesions, the National Cancer Institute initiated a clinical trial in 2002 to determine whether LDCT screening, as compared to CXR, could reduce lung cancer (LCa) mortality.

Criteria for inclusion included at least a 30-year pack history of cigarette smoking, but if patients had signs of potential current LCa (e.g., hemoptysis, unexplained weight loss), they were not included. Study subjects were randomized to LDCT (n = 26,722) or CXR (n = 26,732) and underwent imaging at baseline, 1 year later, and 2 years later. Over the course of three screenings, 39% in the LDCT group and 16% in the CXR group had positive findings, of these more than 94% were false-positive — i.e., they were not LCa.

Evaluation of positive screening led to the diagnosis of LCa in 1060 of the LDCT group and 941 in the CXR group, so LDCT successfully identified about 13% more LCa. At 6 years of follow-up, LCa-related mortality was 20% lower in the LDCT group than the CXR group, and all-cause mortality was also 6.7% lower (both were statistically significant). Before widespread adoption of LDCT occurs, it has been suggested that cost-effectiveness analyses be performed, especially since the absolute risk reduction in mortality within the total study population was very small (1.31% vs 1.62%).

Comparing Metrics for Identification of Prediabetes

Source: Heianza Y, et al. HbA1c 5·7-6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): A longitudinal cohort study. Lancet 2011; 378:147-155.

Since more than half of newly diagnosed diabetics have one or more of the complications of diabetes already existing by the time of diagnosis, it is clear that we must strive for earlier identification of persons destined to develop diabetes and try to forestall or prevent it. The category "prediabetes" includes persons with impaired fasting glucose ([IFG] = 100-125 mg/dL), impaired glucose tolerance ([IGT] 2-hr PPG = 140-199), or elevated A1c (A1c = 5.7-6.4). In most prior clinical trials of diabetes prevention, inclusion required the presence of IGT, with or without IFG, since IGT was felt to be a better predictor of likelihood to progress from prediabetes to diabetes. In clinical practice, very few prediabetes patients are identified by glucose tolerance testing because of the cumbersome nature of the testing. Because utilization of A1c has only recently been condoned as a diagnostic tool for prediabetes, it is worthwhile to peruse the results of an observational trial that followed adults (n = 6241) without diabetes at baseline and compared the predictive capacity of A1c and IFG.

Over 4.7 years of follow-up, more than twice as many individuals developed IFG (n = 1680) than increased A1c (n = -822), and of course some (n = 410) developed both. The predictive capacity of A1c alone was quite similar to IFG alone, but since the two groups have only modest overlap, A1c and IFG actually define somewhat different populations destined to become diabetic. Hence, the authors suggest that using both measurements at the same time is necessary to capture the largest segment of persons with prediabetes.

Treatment of Depression in Patients with Dementia

Source: Banerjee S, et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): A randomised, multicentre, double-blind, placebo-controlled trial. Lancet 2011;378:403-411.

The evidence base supporting ef-ficacy of antidepressant pharmacotherapy in patients with dementia is sparse and inconsistent. Banerjee et al performed a double-blind, randomized, placebo-controlled trial in patients with dementia and depression to assess the effects of two commonly used antidepressants: sertraline and mirtazapine.

Study subjects were randomized to sertraline 150 mg/d (n = 107), mirtazapine 45 mg/d (n = 108), or placebo (n = 151) with no other changes in their medical regimen. Each active antidepressant was initiated at a low dose and titrated within 4 weeks to a higher dose if depression scores had not substantially improved. Outcomes were measured with the Cornell Scale for Depression in Dementia (CSDD).

At the conclusion of the trial, neither sertraline nor mirtazapine provided improvements in CSDD scores greater than placebo, but side effects were more frequent in the active treatment arms. Although the authors do not provide any specific suggestions about what treatments might be preferred (beyond counseling) in the face of these disappointing results, their outcomes suggest reconsideration of preferred treatment for patients with depression associated with dementia.