Modafinil for Excessive Sleepiness Associated with Shift-Work Sleep Disorder
Source: Czeisler CA, et al. N Eng J Med. 2005;353:476-486; Erratum in: N Engl J Med. 2005;353:1078.
Although persons who work rotating shifts not uncommonly experience transient sleep disturbances, in some individuals who maintain a night-shift jobs, sleep disturbances are persistent and may be accompanied by sleepiness at work. Shift-work sleep disorder (SWSD) is defined as excessive sleepiness during night work, coupled with daytime insomnia. Estimates suggest that as many as 5-10% of night-shift workers experience SWSD. SWSD may be associated with diverse consequences, including depression, motor-vehicle accidents, and missed social activities.
Modafinil (MOD), which is classified as a wakefulness-promoting agent’, is indicated to improve wakefulness in patients with excessive daytime sleepiness associated with narcolepsy, obstructive sleep apnea, and SWSD.
Czeisler, et al performed a randomized placebo-controlled trial in SWSD patients (n = 209) of MOD 200 mg daily, administered prior to each work shift for 3 months.
MOD treatment improved sleep latency time, overall clinical symptoms, psychomotor vigilance and motor vehicle accident or near-accidents experiences to a statistically significant degree. Although these are encouraging results, a meaningful degree of excessive sleepiness and impaired performance at night remained in treated individuals, suggesting that there is need for further evolution in management of SWSD.
Acupuncture in Patients with OAK
Source: Witt C, et al. Lancet. 2005;366:136-143.
Currently available validated treatment options for osteoarthritis of the knee (OAK) include acetaminophen, NSAIDs (systemic and topical), glucosamine, chondroitin, opioid analgesics, exercise, physical therapy, and with advanced disease, surgery. Increasingly, the cardiovascular and GI risks of NSAIDs are causing clinicians to reconsider the risk-benefit ratio of various therapies, and seek alternative interventions.
Previous data about the role of acupuncture (ACU) in OAK has suggested that ACU is superior to placebo for pain reduction in OAK, but the data is comprised primarily of small trials with brief follow-up (eg, 3 months). To provide more definitive insight, a large, long-term trial began enrollment in March, 2002.
A total of 294 middle-aged OAK patients were enrolled and randomly assigned to ACU, sham ACU (needles placed at distant, non-acupuncture sites) or placebo. Subjects received 12 sessions of treatment over 8 week’s time, and were followed for 52 weeks.
At 8 weeks, there was a statistically significant difference in pain and function favoring ACU. At 26 and 52 weeks, between-group differences were no longer statistically significant. Acupuncture is effective in reducing pain and increasing functionality in sufferers of OAK.
Risk of Prostate Cancer-Specific Mortality Following Biochemical Recurrence after Radical Prostatectomy
Source: Freedland SJ, et al. JAMA. 2005;294:433-439.
Although radical prostatectomy (RPT) is often curative for prostate cancer (PCA), more than one third of men will experience a recurrence of PSA elevation, indicating likely eventual clinical disease recurrence. The interval after which clinical disease recurs, once a recurrence of PSA elevation is noted, is highly variable: a previous report of 131 men found the median time metastasis was 8 years, and from metastasis to death, 5 years.
In order to better predict PCA-related mortality, men who had undergone RPT for PCA (n = 379) and sustained a PSA recurrence were retrospectively studied in reference to their PSA doubling time and its relationship to outcomes. Gleason scores and time from RPT to PSA recurrence were also studied, and entered into multifactorial analysis.
Each of the three factors was found associated with risk of PCA mortality. Of the three factors, having a PSA doubling time of less than 3 months was associated with the most steep decline in survival. A risk prediction table, using the combined impact of all three factors, was developed as a result of the study. The combination of PSA doubling time, Gleason score, and time to PSA recurrence provides an opportunity for refined risk stratification, allowing patients who might benefit from more aggressive treatment to select it.
Gabapentin for Hot Flashes for Women with Breast Cancer
Source: Pandya KJ, et al. Lancet. 2005;366:818-824.
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.
CHF: Risk-Treatment Mismatch
Source: Lee DS, et al. JAMA. 2005;294:1240-1247.
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.
Diagnosing DPN: The Tuning Fork Wins!
Source: Meijer JWG, et al. Diabetes Care. 2005;28:2201-2205.
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.’
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!
Although persons who work rotating shifts not uncommonly experience transient sleep disturbances, in some individuals who maintain a night-shift jobs, sleep disturbances are persistent and may be accompanied by sleepiness at work.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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