Clinical Briefs in Primary Care

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%).

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 efficacy 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.

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.

Accuracy of Stated Energy Contents of Restaurant Foods

Source: Urban LE, et al. Accuracy of stated energy contents of restaurant foods. JAMA 2011;306:287-293.

Eating out has increased in the general population, and is associated with increased body mass index. Indeed, United States data suggest that more than one-third of all daily calories are provided from restaurants. If clinicians and their patients want to make more healthful choices when eating out, they must rely to some degree on the listed caloric content of these foods, but have little assurance that such listings are accurate.

Urban et al performed bomb calorimetry on 269 food items from 42 different restaurants, and compared calorimetry results with caloric content listed by restaurants.

Nineteen percent of the sampled foods were substantially (more than 100/kcal) above their listed energy content when tested with calorimetry. At the highest decile of discrepancy, foods averaged greater than 250 kcal/portion more than their restaurant listings indicated. It is estimated that eating an extra 100 kcal/d on a chronic basis could result in 5-15 kg of weight gain per year. Encouragingly, the overall food caloric assessments stated in restaurants were reasonably accurate; in the minority of cases where inaccuracies underestimate caloric content, health-conscious consumers may be getting more than they bargained for.

The Past and Future Burdens of Violence Against Women

Source: Rees S, et al. Lifetime prevalence of gender-based violence in women and the relationship with mental disorders and psychosocial function. JAMA 2011;306: 513-521.

More than 20% of adult American women report being victims of rape, intimate partner violence, or stalking. Limitations of previous data sets preclude identifying associations between lifetime experiences of violence and subsequent mental health issues.

Rees et al performed an analysis of data from the second Australian National Mental Health and Well-being Survey, which included 4451 adult women ages 16-85. The overall lifetime prevalence of any mental disorder (as per DSM–IV criteria) was 37.8% including anxiety disorder (24.6%), mood disorder (18.3%), substance use disorder (13.9%), and post-traumatic stress disorder (9.8%). One or more of the above mentioned forms of violence was reported by 27.4% of these same women.

Data analysis found that victims of violence were more likely to also experience mental health disorders; additionally, the severity of these victims' mental health disorders was greater, as was the likelihood that more than one mental health disorder would ensue. The authors suggest that the magnitude of the burden of violence against women and its mental health sequelae merit an enhanced public health focus on the problem.

Does Androgen Deprivation Improve Outcomes for Localized Prostate Cancer?

Source: Jones CU, et al. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med 2011;365:107-118.

Antiandrogen treatment has been shown to induce tumor cell regression in some androgen-responsive cancers, including some prostate cancers. Unfortunately, the survival benefits seen in clinical trials with long-term antiandrogens have been tempered by increased adverse effects, including erectile dysfunction and myocardial infarction. Jones et al performed a controlled trial of radiotherapy for men with localized prostate cancer (n = 1979), with or without short-term (4 months) androgen-deprivation treatment (goserelin or leuprolide).

Overall 10-year survival in patients receiving androgen-deprivation treatment was statistically significantly greater than in men who only received radiotherapy (62% vs 57%). Prostate cancer-associated mortality was also superior in the group receiving androgen-deprivation treatment (8% vs 4%). Black men enjoyed the same degree of risk reduction as non-blacks.

Hepatotoxicity did occur in a minority of men treated with androgen-deprivation treatment, but was low-grade in more than 95% of cases. Short-term androgen deprivation improves outcomes in men with localized prostate cancer.