By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker’s bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.
Gabapentin for Hot Flashes for Women with Breast Cancer
The pathophysiology of menopausal hot flashes (HFL) is not fully understood, but restoration of estrogen, with or without progesterone, provides dramatic relief. Recent disenchantment with utilization of hormone replacement therapy (HRT) as a result of the Women’s Health Initiative has left a population of HFL sufferers looking for additional relief measures. Although there remains some controversy over its appropriateness, breast cancer (BCA) is generally considered an absolute contraindication to HRT. Many women with BCA are receiving treatments like tamoxifen, which are associated with induction of HFL whether or not the patient is menopausal.
Gabapentin (GABA) is one of several therapeutic choices that has shown efficacy in reducing HRT. Because it has no direct hormonal effects, GABA becomes a rational consideration for BCA patients, further supported by a favorable pilot study in women with BCA.
Women (n = 420) with BCA and HFL at least twice daily (mean number of daily hot flashes = 8.7) were randomly assigned to GABA 100 mg t.i.d., GABA 300 mg t.i.d., or placebo for 8 weeks. HFL frequency and severity were compared at weeks 4 and 8.
Both doses of GABA provided a statistically significant 33% reduction in HFL severity. For frequency of HFL, only the higher (300 mg t.i.d.) GABA dose was statistically superior to placebo, providing a 44% reduction. GABA was very well tolerated, with only a 3% placebo-subtracted dropout rate. Similar results have been seen with clonidine, but no head-to-head comparisons of clonidine vs GABA have been published.
Pandya KJ, et al. Lancet. 2005;366: 818-824.
CHF: Risk-Treatment Mismatch
Heart failure (CHF) has sometimes been called the 'hemodynamic malignancy,’ since mortality outcomes from the time of diagnosis are as bad as or worse than many cancers. Voluminous trial data support the favorable impact of ACE inhibitors, ARBs, and beta blockers upon CHF mortality. Because studies of other major mortal disease states, eg, acute coronary syndromes, has shown us that patients at highest risk may actually receive less frequent pharmacotherapeutic tools that have been shown to favorably affect mortality, it was not unreasonable to assess whether the treatment of CHF patients is well matched to the severity of their disease.
Using the validated EFFECT heart-failure mortality risk-stratification method (EFFECT = Enhanced Feedback for Effective Cardiac Treatment), Lee et al, examined the predicted 1 year mortality rates of a large population of CHF patients in Ontario, Canada (n = 9,942) at hospital discharge. Then, they looked at the relative frequency with which ACE inhibitors, ARBs, and Beta Blockers were prescribed in those determined to be a low, intermediate, and highest risk of mortality in the next year.
Disturbingly, patients at the highest risk of 1-year mortality were least likely to receive treatment with ACE inhibitors, ARBs, or Beta Blockers. For instance, the frequency of ACE inhibitor prescription for those in low, intermediate, and highest mortality risk were 81%, 73%, and 60%, respectively (P ≤ 0.001 for trend). Even after accounting for potential perceived contraindications to one or more pharmacotherapies, there remained discordance between risk and treatment intensity. Identifying and overcoming clinician barriers to providing appropriate CHF treatment, especially for higher risk patients, is in order.
Lee DS, et al. JAMA. 2005;294: 1240-1247.
Diagnosing DPN: The Tuning Fork Wins!
Diabetes remains the number one cause of limb loss in the United States, to some degree related to diabetic peripheral neuropathy (DPN). Good diabetic control has been shown to reduce the progression of DPN, and early identification may help forestall consequences, if vigilance towards optimum foot care is maintained.
The literature supports the use of a variety of tests to diagnose DPN, including the 128-Hz tuning fork (128 TF), testing the great toe with pin-prick (TPP), cotton swab light-touch testing of the great toe (CST), monofilament testing using the Semmes-Weinstein monofilament on the sole of the foot (MFT), Achilles reflex testing (ART), and nerve conduction velocity testing (NCV). For those of us who haven’t looked at the tuning fork for awhile, the 128TF is the one with the biggest 'ears.’ Smaller tuning forks (higher frequency) are not suitable for vibration testing.
Different combinations of these tests were used to diagnose DPN in patients with diabetic foot ulcers (n = 24), diabetics without known neuropathy (n = 24), and a non-diabetic control group (n = 21).
After comparing various tests, alone and in combination, the authors determined that the predictive value and validity of the 128TF alone is best, and is clearly superior to monofilament testing. I guess it’s time to step back to simplicity!
Meijer JWG, et al. Diabetes Care. 2005;28:2201-2205.