CLINICAL BRIEFS

By Louis Kuritzky, MD

Clinical Assistant Professor, University of Florida, Gainesville

Dr. Kuritzky is a retained consultant for AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Chelsea, Daiichi Sankyo, Forest Pharmaceuticals, Janssen, Lilly, Novo Nordisk, Pfizer, and Sanofi.

High-dose Influenza
Vaccine vs Standard-dose for Seniors

Source: DiazGranados CA, et al. N Engl J Med 2014;371:635-645.

The highest morbidity and mortality consequences of influenza occur in senior citizens. The efficacy of "standard" flu vaccine varies depending on the outcome that is examined. For instance, as has been best demonstrated in nursing home trials, even when standard-dose flu vaccine fails to prevent clinical disease, it mitigates disease severity enough to reduce mortality. Evolving vaccines, such as the high-dose influenza vaccine, are trying to improve on the already impressive results of earlier versions.

High-dose influenza vaccine (HDVax) contains four times the amount of hemagglutinin as standard-dose vaccine (SDVax). It has already been established that higher antibody titers are achieved with HDVax than SDVax, but whether that translates into improved protection from influenza has not been fully clarified.

This very large randomized, double- blind, active-controlled trial (n = 31,989) compared HDVax vs SDVax through two influenza seasons in North America. Both vaccines were highly effective, since < 2% of recipients of either vaccine contracted clinical influenza. HDVax was found to be superior to SDVax for the primary trial endpoint (acquisition of documented clinical influenza), showing a 24% lower frequency than SDVax. As previously demonstrated, higher antibody levels were also achieved with HDVax.

Before we celebrate the 24% risk reduction with HDVax, recall that this is a relative risk reduction. The absolute risk reduction was very small (0.5%), translating into a number needed to treat of 200. Whether using HDVax instead of SDVax is a worthwhile investment — since this trial indicates that 200 persons must be treated with HDVax instead of SDVax to prevent one case of clinical influenza — will require further consideration, especially since there was no difference in mortality between the groups.

Is Type 2 Diabetes Induced by Psychological Stressors?

Source: Virtanen M, et al. Diabetes Care 2014;37: 2091-2097.

Although the commonly recognized primary predictors of type 2 diabetes (T2DM) include obesity and insulin resistance, it is less clear why some folks with obesity and/or insulin resistance progress to T2DM and others do not. Could psychological stress be a predictor? Results from the Whitehall II Cohort Study suggest that this is indeed the case.

The Whitehall II Cohort Study is comprised of adults employed by the London, England, department of civil service (n = 6895 men and 3413 women) followed prospectively. Data were obtained from a subpopulation of this cohort during various cycles (average observation cycle = 5.46 years) from 1991-2009 to ascertain incidence of T2DM in previously non-diabetic subjects. Psychological stress was measured with the General Health Questionnaire (GHQ-30); a GHQ-30 score > 4 was categorized as "stressed." Proclivity to develop diabetes was further stratified into quartiles by the Framingham Offspring T2DM Risk Score (FOTRS).

Among prediabetic adults in the highest quartile of FOTRS, the adjusted odds ratio for developing T2DM was more than 2-fold greater in stressed individuals than in persons with low stress scores. The mechanism(s) by which stress increases progression to T2DM is not understood. The authors posit that interventions designed to prevent progression from prediabetes to diabetes might well show greater consideration for the potential impact of emotional stressors like depression and anxiety.

Distinguishing Malignant Melanoma from Benign Lesions with a Skin Patch Test

Source: Gerami P, et al. J Am Acad Dermatol 2014;71:237-244.

All of us in primary care who have been faced with the dilemma of ascertaining whether a particular lesion on the skin of a patient is benign or malignant know that, in the absence of a biopsy, we can rarely respond with certainty. Of course, we would rather not biopsy a benign lesion unnecessarily because of time, expense, discomfort, and cosmetic concern for the patient. On the other hand, we don’t ever want to mistakenly allow a cutaneous malignancy, particularly malignant melanoma, to stay on the skin without being identified.

Gerami et al report on the use of a skin patch to diagnose melanoma on the basis of mRNA profiles. Having obtained mRNA "signatures" from multiple prior cases of malignant melanoma in their study sample, subjects had an adhesive patch placed above the lesion in question, which was vigorously rubbed to create adhesion of skin cells to the patch, which were then analyzed for mRNA. After removing the patch, lesions were biopsied to confirm their pathology.

The sensitivity of skin patch-retrieved mRNA diagnosis for melanoma was 97.6%. Hence, having a negative skin patch mRNA test essentially excluded melanoma. The authors point out that such technology could meaningfully reduce unnecessary skin biopsies for questionable lesions.