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Source: Etminan M, et al. Am J Med. 2002;112:642-646.
Headache is among the most commonly reported events in placebo-controlled trials of pharmaceutical agents, usually occurring in both the recipients of active drug and placebo. It has not gone unnoticed that, in contrast to some other antihypertensive agents which have been associated with increases in headache, angiotensin II receptor antagonists (ARBs) have often demonstrated reduced headache incidence when compared to placebo.
To clarify whether this favorable effect of ARB upon headache was consistent, Etminan and colleagues analyzed 27 studies, including more than 12,000 patients, who had received ARB treatment in placebo-controlled trials. In addition, trial data had to include headache either as a primary outcome or as one of the listed adverse effects.
Overall, the risk of headache in recipients of ARBs was reduced about one third compared to placebo. This compares favorably with the headache reduction seen in migraine prophylaxis trials using ACE inhibitors (22% reduction).
Although headache was not further delineated in this report by subtype (eg, migraine, tension, cluster), this report suggests that there has been good consistency between studies. To date, there has not been a comparison trial between ACE inhibitors and ARBs.
Effect of Lower Doses of HRT on Bone in Early Postmenopausal Women
Source: Lindsay R, et al. JAMA. 2002;287:2668-2676.
In addition to relief of vasomotor symptoms, postmenopausal hormone replacement therapy (HRT) has been shown to improve bone mineral density (BMD). Traditionally, 0.625 mg of conjugated equine estrogen (CEE) daily, or the equivalent, has been viewed as "standard" dosing. Nonetheless, substantially lower doses (eg, 0.3 mg/d CEE) have been shown to provide relief for vasomotor symptoms, as well as enhance BMD when combined with calcium supplementation. Combined HRT (estrogen + progestogen) studies have suggested that CEE + medroxyprogesterone acetate (MPA), is either neutral, or possibly beneficial for BMD.
In this report, Lindsay and colleagues examined the effects of various doses of CEE (0.3-0.625 mg/d) and MPA (1.5-2.5 mg/d) in healthy postmenopausal women. End points included BMD (spine and hip) and markers of bone turnover (eg, osteocalcin, urinary telopeptides).
All treatments were superior to placebo for BMD in spine and hip, as well as markers of bone turnover. Standard’ dose CEE (0.625 mg/d) alone was superior to CEE 0.3mg/d alone. The addition of MPA had no effect, positive or negative, on BMD except in women using higher dose CEE (0.625 mg/d), in whom the effect was favorable. Lindsay et al conclude that lower dose CEE-MPA does reduce bone loss in postmenopausal women.
Pulse Pressure and Cardiovascular Disease-Related Mortality
Source: Domanski M, et al. JAMA. 2002;287:2677-2683.
The population of men screened for participation in the Multiple Risk Factor Intervention Trial (MRFIT) has provided a large population (n = 342,815) from which to derive important observational epidemiologic data. Men were screened from 1973 until 1975, and followed for cardiovascular mortality until 1996.
Pulse pressure ( = SBP-DBP) has been increasingly recognized as a predictive factor for cardiovascular morbidity and mortality. Pulse pressure rises as large artery elasticity is lost. Hence, an increased pulse pressure reflects increasing arterial rigidity.
In the MRFIT screenees, the SBP and DBP showed a stronger association with cardiovascular mortality than pulse pressure. Using any 2 of the 3 variables (DBP, SBP, pulse pressure) was superior to any one individual variable for predicting adverse cardiovascular outcome. Intuitively, it can be recognized that at lower levels of blood pressure (eg, 120/50), the pulse pressure alone (= 70), even though the same as that seen at 160/90 (= 70) would not likely reflect cardiovascular risk. However, in support of the predictive role of pulse pressure, in this population the men suffering elevated SBP with the LOWEST DBP (thus, with the highest pulse pressure), experienced the highest cardiovascular mortality rates.
Comparative Efficacy of Insect Repellents Against Mosquito Bites
Source: Fradin MS, Day JF. N Engl J Med. 2002;347:13-18.
Mosquitoes are typically viewed as nuisance pests, though in the United States they are responsible for a variety of types of encephalitis, and globally, for malaria. Since mosquito bites are potentially consequential, insect repellant (IRP) efficacy is a clinically relevant issue.
Testing was performed by having volunteers insert an arm into a cage containing 10 unfed mosquitoes, and measuring the time until a first bite was received. For instance, subjects would place an untreated arm into the cage, record the time to first bite, and then insert an IRP-treated arm. If the arm was not bitten within 20 minutes, it was reinserted for 1 minute every 15 minutes until a bite occurred.
DEET provided the longest protection, but this was a concentration-related phenomenon, with a 24% DEET solution providing complete protection for 302 minutes, compared with only 88.4 minutes for a 4.75% DEET formulation. On the other hand, controlled-release DEET did not appear to favorably affect performance.
Non-DEET formulations, such as soy-based oil and citronella, were unable to provide comparable protection to high-concentration DEET. For instance, citronella provided less than 20 minutes protection. Repel Lemon Eucalyptus Insect Repellant (marketed after this study was completed), was also tested, and provided substantially less protection than high-concentration DEET, but more than citronella and soy-based products. Despite consumer assertions to the contrary, Skin-So-Soft provided only 9.6 minutes of protection. Fradin and Day conclude that DEET should remain the gold standard for mosquito bite protection, and that the product is safe and well tolerated when used as indicated.
Reduction in Self-Monitoring of Blood Glucose in Type 2 Diabetes Results in Cost Savings and No Change in Glycemic Control
Source: Meier JL, et al. Am J Manag Care. 2002;8:557-565.
Nationally, in the us veterans Administration (VA) population, diabetes (DM) is responsible for 24% of pharmacy costs. The Northern California Health Care System VA (data source for this study) alone has expended as much as $450,000 annually for glucose testing strips. In an effort to examine the effect of reduced self-monitoring of blood glucose (SMBG) in type-2 diabetes (DM2), which comprises 95% of the diabetic population, the VA instituted a policy of 50 SMBG strips each 90-day period. This constituted an approximate halving of previous testing strip use. Clinicians were able to "override" the reduced number of testing strips for persons requiring more frequent monitoring in special circumstances (eg, monitoring hypoglycemia, concurrent illness days). Adequacy of control was measured by monitoring of A1C over time for 1 year.
Reduced frequency of SMBG had no measurable effect on A1C. Cost savings averaged $8800 per month, even when clinicians used their "override" privilege to provide extra testing strips. The ideal frequency of SMBG remains uncertain, but prescribing of 50 strips per 90 days does not appear to compromise glucose control in a population previously using twice that amount.
Vasectomy and Risk of Prostate Cancer
Source: Cox B, et al. JAMA. 2002; 287:3110-3115.
Beginning about 1990, case-control data suggested that vasectomy (VAS) was associated with an increased risk of prostate cancer (PCA). Subsequently (1993), 2 large cohort studies indicated a doubling of PCA risk when measured 20 years postsurgery. Such information prompted some clinicians to screen vasectomized men for PCA with greater vigor, and to suggest that men with strong PCA family history consider alternative contraceptive methods.
There remains still some public and professional uncertainty about whether VAS is associated with increased PCA risk.
Because New Zealand has the highest VAS prevalence in the world, and maintains a national registry of PCA, it provides an appropriate resource for clarification of the VAS:PCA relationship. From 1996-1998, the New Zealand National Cancer Registry identified 923 new cases of PCA in men aged 40-74, which were compared with 1224 age-matched controls. Although family history (first-degree relative) was positively associated with an increased PCA risk, VAS was not. In fact, there was a trend toward PCA being LESS frequent in those with history of VAS.
Cox and colleagues indicate that the large size of the study population provided a statistical power of 99% to detect a statistically significant relative risk of 1.5 or greater. The fact that data had followed patients up to 25 years is additional reassurance that VAS does not increase risk of PCA, even after an extremely long lag period.