This web page column will present the most up-to-date research results on prevention and treatment methods as indicated in a professional literature review. We will report on meta-analysis studies that look at all research results on a particular topic and try to tease out robust trends. While it may not be the final answer, the results represent the available research evidence and from a logical point of view, the conservative approach that would give the best results for the disease in question. The information cited below is for our reader's personal consumption. It is not a substitute for consulting your physician.
Evidence-Based Medicine and Statistical Terms
(7/25/08)- (These terms will prove helpful when you read some of the original research studies referred to in the research literature.)
Sensitivity (Sn): percentage of patients with disease who have a positive test for the disease in question
Specificity (Sp): percentage of patients without disease who have a negative test for the disease in question.
Predictive value-positive and negative (PV+/PV-): Percentage of patients with a positive or negative test for a disease who do or do not have the disease in question.
Pretest probability: Probability of disease before a test is performed.
Post-test probability: Probability of disease after a test is performed.
Likelihood ratio (LR): LR>1 indicates an increased likelihood of disease, LR<1 indicates a decreased likelihood of disease. The most helpful tests generally have a ratio of less than 0.2 or greater than 5.
Relative risk reduction (RRR): The percentage difference in risk or outcomes between treatment and control groups. Example: if mortality is 30% in controls and 20% with treatment, RRR is (30-20)/30=33%.
Absolute risk reduction (ARR): The arithmetic difference in risk or outcome between treatment and control groups. Example: if mortality is 30% in controls and 20% in treatment, ARR is 30-2-=10%.
Number needed to treat (NNT): The number of patients who need to receive an intervention instead of the alternative in order for one additional patient to benefit. The NNT is calculated as: 1/ARR. Example. If the ARR is 4%, the NNT=1/4%=1/0.04=25.
95 percent confidence interval (95%CL): An estimate of precision. If a study is repeated 100 times, the results will fall within this range 95 times.
Systematic review: A type of review that uses explicit methods to comprehensively analyze and qualitatively synthesize information from multiple studies.
Meta-analysis: A type of systematic review that uses rigorous statistical methods to quantitatively synthesize the results of multiple similar studies.
(8/2/05)- The Guide to Clinical Preventive Services 2005, published by the Agency for Healthcare Research and Quality, is an updated version of evidence-based clinical guidelines from the U. S. Preventative Services Task Force (USPSTF). Free single copies are available online at http://www.ahrq.gov/clinic/pocketgd.htm or by calling the AHRQ Publications Clearinghouse at 1-800-358-9295.
Those readers seriously interested in evidence based medicine should link to <http://www.shef.ac.uk/uni/academic/R-Z/scharr/ir/neting.html>. This site is an index of online sources of evidence based medicine complete with commentaries. Andrew Booth produces it at the School of Health and Related Research.
Acute Migraine Treatment
(3/31/02)- Ferrari (1) and colleagues suggest that "an antiinflammatory drug prospective"(the triptan class of drugs) is the most effective acute migraine treatment but also alert users to the fact that they are associated with more intense adverse effects. They indicate that 2.5 mg of naratriptan offers good tolerability coupled with slower onset of improvement, which can be useful in patients with mild to moderate migraine. They point to 2.5 and 5 mg zolmitriptan as good alternatives. See below for further treatment guidelines.
Triptans have 3 main mechanisms of action: cranial vasoconstriction, peripheral trigeminal inhibition and inhibition of transmission through second order neurons of the trigeminocervical complex. Goadsby (2), in his review in Progress in Neurobiology 2000; 62:509-522, found them to have evidence-based prescribing instructions, well established efficacy, modest side effects and a good safety record. However, please note that they are contraindicated when cardiovascular disease is present.
There are now seven different triptans available. Head to head comparisons by the Ferrari group (1). indicated the following conclusions:
The Ferrari (1) group then developed evidenced-based implications from this study as guidelines for treatment. Below we present these guidelines for our readers’ information when discussing treatment with their physician:
The Adelman (3) group compared the seven triptans using stringent outcome measures: ("percentage of patients pain-free at 2 hours, symptom-free at 2 hours (no pain, nausea, photophobia, phonophobia, vomiting, or functional disability), 24-hour sustained pain-free (no headache at 2 hours, no recurrence, and no additional antimigraine medications for 24 hours)". They concluded that: "Oral rizatriptan 10 mg was more effective than oral sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures of pain-free response at 2 hours, symptom-free response at 2 hours, and 24-hour sustained pain-free response." This appears to confirm the Ferrari et al results. (Listed at the end of this article are the head-to-head results of the Adelman study comparing the various triptans.)
Migraine headache is defined as "a common, chronic, multifactorial neurovascular disorder, typically characterized by recurrent disabling attacks of severe headache, autonomic nervous system dysfunction and, in up to one third of patients, neurological aura symptom".
The list of common migraine triggers continues to grow. The following have been implicated: air pollution, red wine, bright light, caffeine withdrawal, cheese, chocolate, cigarette smoke, estrogen, menstruation, missed meals, monosodium glutamate, nitrates, perfume, progesterone, red grapes, sleep disturbances (too much or too little), and stress.
Lipton (4) and his group published an epidemiological study, which determined the prevalence and distribution of migraine in the United States as well as current patterns of health care use. The results of this study were: "The 1-year prevalence of migraine was 17.2% in females and 6.0% in males. Prevalence was highest between the ages of 30 and 49. Whereas 48% of migraine sufferers had seen a doctor for headache within the last year (current consulters), 31% had never done so in their lifetimes and 21% had not seen a doctor for headache for at least 1 year (lapsed consulters). Of current or lapsed consulters, 73% reported a physician-made diagnosis of migraine; treatments varied. Of all migraine sufferers, 49% were treated with over-the-counter medications only, 23% with prescription medication only, 23% with both, and 5% with no medications at all. It would appear that a treatable disease is not being treated, with needless suffering being endured.
In the search to find a basis for migraines, Schecter et al (5) sought to confirm clinic-based studies suggesting that migraine is associated with abnormal autonomic nervous system (ANS) function. The results of their review indicated, "migraineurs with disabling attacks may be prone to (ANS) hypofunction. These findings may suggest that ANS dysfunction either may be a risk factor for migraine headaches or be a consequence of frequent disabling attacks. Moreover, ANS dysfunction and migraine may share a common neural substrate."
1. Ferrari MD, Roon KI, Lipton RB, Goadsby PJ. Oral triptan (serotonin 5-HT1B/1D agonists) in acute migraine treatment: a meta-analysis of 53 trials. Lancet 2001; 358:1668-1675.
2. Goadsby, PJ. The Pharmacology of Headache. Progress in Neurobiology 2000; 62:509-522,
3. Adelman JU, Lipton RB, Ferrari MD, Diener H.–C., McCarroll KA, Vandormael K, Lines CR. Comparison of rizatriptan and other triptans on stringent measures of efficacy. Neurology 2001; 57:1377-1383
4. R. B. Lipton, MD, A. I. Scher, PhD, K. Kolodner, PhD, J. Liberman, PhD, T. J. Steiner, MB PhD and W. F. Stewart, PhD. Migraine in the United States: Epidemiology and patterns of health care use. Neurology 2002; 58:885-894
5. Shechter A, Stewart WF,. Silberstein SD, Lipton RB. Migraine and autonomic nervous system function: A population-based, case-control study. Neurology 2002; 58:422-427
*Results from the Adelman Study: — "More patients taking rizatriptan 10 mg were pain-free at 2 hours than were patients taking sumatriptan 100 mg (40% vs 33%, p = 0.019), sumatriptan 50 mg (40% vs 35%, p = 0.009), sumatriptan 25 mg (38% vs 27%, p < 0.001), naratriptan 2.5 mg (45% vs 21%, p < 0.001), and zolmitriptan 2.5 mg (43% vs 36%, p = 0.041). More patients taking rizatriptan 10 mg were symptom-free at 2 hours than were patients taking sumatriptan 100 mg (31% vs 22%, p = 0.002), sumatriptan 50 mg (33% vs 28%, p = 0.003), sumatriptan 25 mg (33% vs 24%, p < 0.001), naratriptan 2.5 mg (30% vs 11%, p < 0.001), and zolmitriptan 2.5 mg (31% vs 24%, p = 0.042). More patients taking rizatriptan 10 mg had a 24-hour sustained pain-free response than did patients taking sumatriptan 100 mg (27% vs 23%, p = 0.112), sumatriptan 50 mg (30% vs 26%, p = 0.015), sumatriptan 25 mg (27% vs 20%, p = 0.005), naratriptan 2.5 mg (29% vs 17%, p = 0.004), and zolmitriptan 2.5 mg (32% vs 24%, p = 0.013)"
Research results indicate that plasma fibrogen levels may be associated with cardiovascular events. Dr. Marasca et al did a meta-analysis of studies conducted between 1984 and 1998, looking at the relationship between high levels of plasma fibrogen and fatal and/or nonfatal cardiovascular events in both the general population and in patients with previous cardiovascular events. He found 22 studies that met the criteria for robust results based on optimal standards of research. The analysis indicated that "fibrogen measurement should be encouraged to refine the overall risk profiles of individuals and to better tailor preventive measures." It is an independent risk factor for cardiovascular disease. Fibrogen is involved in platelet aggregation and blood viscosity. Bezafibrate is a leading drug to decrease the risk of platelet aggregation and lowers the risk of reoccurrence of myocardial infarction.
(Ref: Maresca G, Di Blasio A, Marchioli R, Di Minno G. Measuring Plasma Fibrinogen to Predict Stroke and Myocardial Infarction: an update. Biology 1999; 19:1368-1377)
Another factor that is associated with high risk for cardiovascular disease is homocysteine levels. Data would suggest that mild to moderate elevations in plasma homocysteine levels in healthy subjects activate coagulation, modify the adhesion properties of endothelium and impair the vascular responses of L-arginine which could result in arteriosclerotic cardiovascular disease. Dr. Nappo and his group used 800 IU of vitamin E and 1000 mg of ascorbic acid to block the effects of increased levels of homocysteine. This is another of those studies that indicate the antioxidant effects of vitamin E and ascorbic acid as a preventative technique.
(Ref: Nappo F, De Rosa N, Marfella R, De Lucia D, Ingresso D, Perma AF, Fargoti B, Guigliana D. Impairment of Endothelial Function by Acute Hyperhomocysteinema and Reversal by Antioxidant Vitamins. JAMA 1999; 281(22): 2113-2118. Also see Omenn GS, Beresford SAA, Motulsky AG. Preventing Coronary Heart Disease: B vitamins and homocysteine. Circulation 1998; 97:421-424.)
For those interested in further studies of the role of Vitamin E as a factor in lowering risk of coronary heart disease, we would suggest you check the following references:
These studies indicate that vitamin E at pharmacological doses may reduce rate of nonfatal myocardial infarction, but suggest that its effects on cardiac or all-cause mortality is unclear. The mechanism by which Vitamin E manifests its protective effect in coronary heart disease is not known. What is known is that Vitamin E inhibits the proliferation of smooth-muscle cells in vitro and that it increases the resistance of low-density lipoprotein to oxidation when it is added to plasma or administered to humans. Further research indicates that platelets from persons taking Vitamin E supplements have markedly reduced adhesiveness to collagen. One would assume that it would effect the incidence of strokes. Yet Ascherio et al in the Annals of Internal Medicine 1999; 30 (12): 963-970, found no association between Vitamin E or Vitamin C consumption and risk for total or ischemic stroke. This was a study where 43,738 male health professionals, age 40 to 75, were followed for 8 years for incidence of stroke. Their definition of stroke was "a typical neurological deficit of sudden or rapid onset that lasted at least 24 hours and was attributable to a cerebrovascular event". The classification of stroke used included ischemic (embolism or thrombosis), subarachoid hemorrhage, intracerebral hemorrhage or unknown cause. They do point out that research literature is robust in indicating intake of fruits and vegetables are inversely associated with risk for stroke in various kinds of studies including ecological, prospective study and their own study of men.
Ref: Ascherio A, Rimm EB, Hernan M, Giovannucci E, Kawachi I, Stampfer M & Willet W. Relationship of Consumption of Vitamin E, Vitamin C and Carotenoids to Risk for Stroke among Men in United States. Annals of Internal Medicine 1999; 30 (12): 963-970.
References for those interested in the role of fruits and vegetables:
FOR AN INFORMATIVE AND PERSONAL ARTICLE ON PRACTICAL SUGGESTIONS WHEN SELECTING A NURSING HOME SEE OUR ARTICLE "How to Select a Nursing Home"
Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated July 25, 2008
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