PrimeCuts: This Week in the Journals

February 2, 2009

wintersunset.JPGCommentary by Sherley Abraham MD PGY-3

Faculty Peer Reviewed

This week we reflect on the interplay in life which is showcased by two football teams. In medicine, it plays out between two drugs, newer markers and standard guidelines, or lifestyle and disease. Each ailment calls for its own chicken soup, which it turns out, actually does work for the common cold. Of course, in football, one team emerges as victor….go Steelers and the NFL…but onto BNP.

The search continues for a simple approach to titration of therapy for heart failure and BNP appears not to be the answer quite yet. In the TIME-CHF study in JAMA, 499 elderly patients with heart failure were randomized to BNP-guided therapy versus symptom-guided therapy. Over 18 months, escalation of therapy was aimed at reducing BNP levels and symptoms in the BNP-guided group as opposed to reducing symptoms to class II or below in the standard symptom-guided group. The two groups were found to have similar overall survival rates (84% in the BNP group and 78% in the symptom-guided group), similar survival free of hospitalization from any cause (41% in BNP group and 40% in symptom-guided group), as well as similar quality of life. In a secondary analysis, there were fewer heart failure hospitalizations in the BNP group, but this was selective to the 60 to 75 year-olds and not those 75 or above. BNP strategy appears to not be helpful in patients above the age of 75, and may actually be harmful.

Patients 75 and older age are of particular concern because of the growing numbers in that age group. The differences in effects among age groups are highlighted by an editorial by Piña and O’Connor. The uptitration of medications using the BNP-guided approach led to more adverse events of hypotension, renal failure, and hyperkalemia in the group above 75. At baseline, the older group is noted to have more comorbidities, including hypertension, elevated creatinine, atrial fibrillation, and prior stroke. They also had a higher EF meaning their heart failure was likely a mixed syndrome of systolic and diastolic dysfunction. The authors state that diastolic heart failure (aka preserved systolic function failure) is a different entity altogether.

If you’re considering donating a kidney, this report from NEJM is going to be especially interesting to you. In the latest issue, the long-term consequences of kidney donation were carefully examined up to 45 years after uninephrectomy. In the period between 1963 and 2007, 3698 kidney donors were studied for vital status and risk of ESRD, and from 2003 to 2007, 255 donors were further examined for GFR, urinary albumin, hypertension, general health, and quality of life. The Minnesota study found that survival and risk of renal disease was similar among donors and matched controls. In the subgroup analysis, reduced GFR was associated with older age and higher BMI, the same factors as in the general population, while albuminuria was associated with longer time since donation, but was also similar to controls. Donors were found to have better quality of life scores than controls, which may reflect the fact that they were carefully screened at time of donation. In a NEJM editorial, Tan and Chertow point out that the rigorous screening of kidney donors for co-morbidities and the homogenous population in this study should make reader cautious about extrapolating the data to other groups.

As physicians, memorizing facts is what we do. If you want a quick way to improve your memory, some recent data shows that less is more. A study released in the latest issue of PNAS found that calorie reduction led to improved memory. A group of fifty normal to overweight people aged 50 to 72 were split into three groups. The first group cut calories by 30% by eating smaller portions, the second maintained calories but increased unsaturated fat, and the third group made no changes. There was a 20% improvement in memory performance in the group which restricted their calories, while the other two groups had no change. The researchers propose that the improvement in memory is due to decreased insulin which leads to better receptor sensitivity, improved signaling, and overall decreased inflammation. The New York Times commentary speculates that the unsaturated fat group may have shown memory improvements if their diet had fish high in omega-3 fatty acids.

Want another reason to lose weight? Weight reduction may help the loss of memories and the involuntary loss of urine. A study in NEJM by Subak and others showed that weight loss reduced the frequency of urinary incontinence. The study randomly assigned 338 overweight and obese women with urinary incontinence to an intensive weight-loss program or a structured education program. After 6 months, the women in the intervention group had an average weight loss of 7.8 kg and a 47% decrease of incontinence episodes. The control group lost an average of 1.5 kg and had a 28% decrease of incontinence. This improvement in urinary incontinence is yet another health benefit of weight loss.

Another common chronic disease is depression, and a meta-analysis in the Lancet compares a dozen new-generation antidepressants. The study reviewed 117 RCTs from 1991 to 2007 and the main outcomes were response to treatment or discontinuation. In terms of efficacy, mirtazepine, escitalopram, venlafaxine, and sertraline were better than duloxetine, fluoxetine, fluvoxamine, and reboxetine. Factoring in acceptability, escitalopram and sertraline led the pack, and considering cost, sertraline was left as the best choice when initiating treatment.

More on drugs–this time, two other common medications, PPIs and Clopidogrel, were reported as having a possible interaction by the Canadian Medical Association Journal. The link is based on a population-based case control study following patients between 2002 and 2007 after hospital discharge after acute MI. The study suggests PPIs may be a cause of Clopidogrel resistance which occurs in 5 to 15% of patients and increases the risk of readmission for another MI. Some PPIs block the bioactivation of cytochrome P450 2C19, which is required to activate Clopidogrel to its active metabolite. The exception was Pantoprazole, which does not inhibit the cytochrome P450 2C19 and was not associated with increased risk of reinfarction.

Lastly, as winter cold season keeps Kleenex in business, a study in Rhinology quoted by the Times, shows that drinking hot liquids provides symptomatic relief for the flu or common cold by loosening secretions and clearing congestion. In this study of 30 subjects, there was no objective change in nasal airflow but hot liquids provided relief of runny nose, cough, sneezing, sore throat, chilliness, and tiredness, while the room temperature drink only provided relief from runny nose, cough, and sneezing. The idea that older remedies still prevail in the world of modern medicine is this week’s chicken soup for the blog.

Reviewed by Judith Brenner MD, Associate Editor, Clinical Correlations


Ibrahim HN, et al. Long-term consequences of kidney donation. N Engl J Med. 2009 Jan 29;360(5):459-69.

Tan JC, Chertow GM. Cautious optimism concerning long-term safety of kidney donation. N Engl J Med. 2009 Jan 29;360(5):522-3.

Pfisterer M, et al. BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial. JAMA. 2009 Jan 28;301(4):383-92.

Piña IL, O’Connor C. BNP-guided therapy for heart failure. JAMA. 2009 Jan 28;301(4):432-4.

Witte AV, et al. Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1255-60.

Belluck P. Another Potential Benefit of Cutting Calories: Better Memory. New York Times. 2009 Jan 26.

Subak LL, et al. Weight loss to treat urinary incontinence in overweight and obese women. N Engl J Med. 2009 Jan 29;360(5):481-90.

Cirpiani A, et al. Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis. 2009 Jan 29. Epub

Juurlink DN, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009 Jan 28.

Sanu A, Eccles R. The effects of a hot drink on nasal airflow and symptoms of common cold and flu. Rhinology. 2008 Dec;46(4):271-5.

O’Connor A. The Claim: Hot Liquids Can Ease Symptoms of a Cold or Flu. New York Times. 2009 Jan 26.