Risk for Zoster from the Vaccine in Immunosuppressed Persons
Source: Zhang J, et al. JAMA 2012;308: 43-49.
The prevailing wisdom suggests that because herpes zoster vaccine (ZOS) is a live virus, it should not be administered to persons receiving immunosuppressive treatments, such as biologic agents or methotrexate for rheumatoid arthritis, or chronic prednisone therapy of 20 mg/d or more. The concern is that instead of mounting an immune response to the vaccine, vaccinees might actually experience a case of shingles as a result of the vaccine.
To examine the real-life risk of an acute zoster infection after ZOS, a retrospective analysis was performed on a large Medicare database (n = 463,541) of persons with a diagnosis of rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease. Any one of these disorders would be commonly treated with immunosuppressive agents, corticosteroids, or both.
The analysis looked at the number of cases of shingles within 42 days of ZOS, anticipating that if the live virus vaccine had induced shingles, it should certainly have happened within that 6-week window after vaccination.
No increased incidence of shingles was seen in ZOS recipients, even in patients on biologics. Indeed, ZOS was associated with a 39% lower risk of shingles during the 42-day window of observation, and a reduced risk during the subsequent 2 years (median) of follow-up. ZOS appears to be beneficial even in immunocompromised individuals, and the authors challenge the propriety of current recommendations that advise against ZOS administration in such populations.
Cerebral Aneurysms: What's in Your Patient's Future?
Source: UCAS Japan Investigators. N Engl J Med 2012;366:2474-2482.
The UCAS (unruptured cerebral aneurysm) Japan study began enrolling patients with incidentally discovered cerebral aneurysms (CRAs) for an observational study in 2001. The primary purpose of the study was to better delineate the natural history of incidentally discovered CRAs (as opposed to discovery through neurologic signs or symptoms). Prior to this trial, it had been generally recognized that CRAs < 7 mm rarely rupture, and that posterior circulation CRAs have a greater risk than anterior.
This prospective cohort study included patients (n = 6413) with incidentally discovered CRA and minimal, if any, disability. Subjects were followed for up to 8 years. During this interval, the annual rate of CRA rupture was approximately 1%. When rupture did occur, it was fatal in 35% of cases, or led to moderate-severe disability in another 29%.
The most important predictive factors for rupture were size of the CRA, age, and gender (females are at greater risk). For example, when compared with lesions < 7 mm, a 7-9 mm lesion had a three-fold increase of rupture, and a lesion > 10 mm had a nine-fold increased risk. Risk in women was 1½ times as great as men, and persons over age 70 were 21% more likely to experience aneurysm rupture. Because the entire population of enrollees was Japanese, the generalizability of these results may have limitations, but nonetheless provide perhaps the most accurate mapping of risk factors for rupture of CRAs.
Elucidating the 'Best' Interval for Bone Density Screening in Osteoporosis
Source: Yu EW, Finkelstein JS. JAMA 2012;307:2591-2592.
Once a baseline bone mineral density (BMD) has been obtained, it is unclear when the study should be repeated. For one thing, the literature suggests that only about 30% of bone strength may be attributable to bone density. Additionally, some of the interventional trials using bisphosphonates have found fracture reduction despite continuation of bone density loss over the first year or two of intervention. Finally, the rate at which BMD declines has been linked to the baseline BMD.
For instance, a study that looked at menopausal women (age > 67 years) for progression of BMD loss found some fairly startling results: It would take approximately 15 years for 10% of women with normal baseline BMD (T score < -1.5) to incur sufficient loss of BMD to cross the diagnostic threshold for osteoporosis (T score < -2.5). Similarly, for women with osteopenia (T score -1.5 to -2.0) at baseline, it would require 5 years for 10% of them to progress to frank osteoporosis. At the greatest level of osteopenia (T score -2.0 to -2.5), progression to osteoporosis in 10% of women would be expected to occur within 1 year. These projections assume no addition of new risk factors known to accelerate bone loss.
Although it is tempting to get BMD more often, it may not be helpful. Although the data are sufficiently uncertain that the USPSTF has been unable to provide confirmation of a preferred schedule, Yu et al suggest following rescreening intervals for postmenopausal women: for women with normal BMD at baseline, 10 years; for women with mild osteopenia and low FRAX score at baseline, 5-10 years; for women with moderate osteopenia or FRAX score approaching treatment threshold, 2 years.
An Unexpected Connection Between PTSD, ACE Inhibitors, and ARBs
Source: Khoury NM, et al. J Clin Psychiatry 2012;73:849-855.
Several lines of evidence suggest that modulation of the renin-angiotensin-aldosterone system with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) might potentially have positive effects on post-traumatic stress disorder (PTSD). Preclinical data indicate favorable cerebral effects of ARBs, such as stress reduction and anxiolysis. Some ARB trials have reported positive effects on cognition, quality of life, and depression or anxiety.
Khoury et al performed a cross-sectional observational data analysis of PTSD patients (n = 505) comparing symptoms in those who were being treated with an ARB/ACE vs controls (no ARB/ACE treatment). Overall, PTSD symptom scores were almost 25% lower among patients treated with ACE or ARB therapy (P = 0.04).
The better symptom scores among PTSD patients treated with ARB or ACE therapy were not simply due to the fact that hypertension (which is more common in PTSD patients) was treated; no other antihypertensive medications (e.g., calcium channel blockers, diuretics, beta- blockers) were found to have similar favorable effects.
The mechanism through which ACE/ARB treatments impact PTSD is not well established, but may be through modulation of the noradrenergic system.
The Right Amount of Vitamin D to Prevent Fractures
Source: Bischoff-Ferrari HA, et al. N Engl J Med 2012;367:40-49.
Inclusion of vitamin d (VTD) in the regimen for fracture prevention is time honored and condoned by major guidelines. Intuitively, VTD should be helpful, but the analyses of data in reference to this topic are mixed. For instance, although one meta-analysis indicated an 18% reduction in hip fracture if a minimum of 482 IU/d VTD was prescribed, equally prominent data concluded that VTD alone was of no benefit. So, how about further investigation of the subject?
Bischoff-Ferrari et al performed an analysis on 11 double-blind, randomized, controlled trials of oral VTD supplementation (n = 31,022) seeking to determine if supplementation (with or without calcium) reduced hip fracture. According to their analysis, there was no statistically significant reduction in fracture risk in subjects assigned to VTD. Story over? Well, maybe not quite.
First, although hip fracture was not reduced, there was a marginally statistically significant 7% reduction of total non-vertebral fractures. Additionally, when analyzed from the viewpoint of the actual intake of VTD instead of what subjects were assigned to, the picture looks quite different. Specifically, subjects in the highest quartile of actual VTD intake (prescribed supplementation plus dietary intake) enjoyed a statistically significant 30% reduction in hip fracture. For the time being, at least 800 IU/d VTD supplementation is recommended in persons ≥ age 65.
Prevention of Diabetes
Source: Perreault L, et al. Lancet 2012; 379:2243-2251.
It appears that one's ounce of prevention may have to be weighed more carefully to attain the fullest pound of cure. Why? The answer lies in subgroup analysis of recent trials in diabetes prevention.
There have been many diabetes prevention trials, essentially all of which have been successful to a varying degree. Overall, diet and exercise appear to be as efficacious as any other intervention. Pharmacologically, numerous classes of agents have been successfully tried (metformin, thiazolidinedione, alpha-glucosidase inhibitor, etc.). What has been learned is that successful incorporation of diet/exercise or pharmacotherapy over a 4- to 6-year period reduces the likelihood of progressing from prediabetes to diabetes (typically, 6-10%/year) by half or more. But there is more to the story.
After successful treatment (pharmacotherapy or lifestyle), the majority of those who are prevented from progressing to frank diabetes still fulfill criteria for prediabetes (A1c 5.7-6.4). Between 20-50% of treated subjects are restored to currently recognized normal glucose levels.
The analysis by Perrault et al indicates that persons with prediabetes in whom normal glucose homeostasis was restored are half as likely to progress to frank diabetes over a 3-year, post-trial observation period as individuals whose glucose control was improved, but still reflected prediabetes. Striving for the best glucose control in prediabetes may have long-term benefits.
Risk for Zoster from the Vaccine in Immunosuppressed Persons; Cerebral Aneurysms: What's in Your Patient's Future?; Elucidating the 'Best' Interval for Bone Density Screening in Osteoporosis; An Unexpected Connection Between PTSD, ACE Inhibitors, and ARBs; The Right Amount of Vitamin D to Prevent Fractures; Prevention of DiabetesYou have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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