By L. Dimitar. Holy Family College.

Only two of the seven trials showed a statistically significant benefit (in term s of survival of the infant) but the im provem ent in precision (i order robaxin 500mg overnight delivery muscle relaxant food. This m etaanalysis showed that infants of steroid treated m others were 30–50% less likely to die than infants of control m others buy discount robaxin 500 mg line muscle relaxant little yellow house. If you have followed the argum ents on m etaanalysis of published trial results this far, you m ight like to read up on the m ore sophisticated technique of m etaanalysis of individual patient data, which provides a m ore accurate and precise figure for the point 132 PAPERS TH AT SU M M ARISE OTH ER PAPERS estim ate of effect. In the language of m etaanalysis, hom ogeneity m eans that the results of each individual trial are com patible with the results of any of the others. H om ogeneity can be estim ated at a glance once the trial results have been presented in the form at illustrated in Figures 8. British Regional HeartBritish Regional Heart BUPABUPA GothenburgGothenburg MRFIT screeneesMRFIT screeness Renfrew-PaisleyRenfrew-Paisley WhitehallWhitehall HonoluluHonolulu Central SwedenCentral Sweden IsraeliIsraeli Pooling projectPooling project 0 10 20 30 40 50 % Reduction Figure 8. The definitive test involves a slightly m ore sophisticated statistical m anoeuvre than holding a ruler up against the blobbogram. The one m ost com m only used is a variant of the chi square ( 2) test (see Table 5. The 2 statistic for heterogeneity is explained in m ore detail by Sim on Thom pson,30 who offers the following useful rule of thum b: a 2 statistic has, on average, a value equal to its degrees of freedom (in this case, the num ber of trials in the m etaanalysis m inus one), so a 2 of 7. There m ay, for exam ple, be known differences in m ethodology (for exam ple, authors m ay have used different questionnaires to assess the sym ptom s of depression) or known clinical differences in the trial participants (for exam ple, one centre m ight have been a tertiary referral hospital to which all the sickest patients were referred). There m ay, however, be unknown or unrecorded differences between the trials which the m etaanalyst can only speculate upon until he or she has extracted further details from the trials’ authors. Rem em ber: dem onstrating statistical heterogeneity is a m athem atical exercise and is the job of the statistician but explaining this heterogeneity (i. The results are expressed as the 134 PAPERS TH AT SU M M ARISE OTH ER PAPERS percentage reduction in heart disease risk associated with each 0. The horizontal lines represent the 95% confidence intervals of each result and it is clear, even without being told the 2 statistic of 127, that the trials are highly heterogeneous. The m etaanalyst m ust return to his or her prim ary sources and ask, "In what way was trial A different from trial B, and what do trials C, D and H have in com m on which m akes their results cluster at one extrem e of the figure? In this exam ple, a correction for the age of the trial subjects reduced 2 from 127 to 45. In other words, m uch of the "incom patibility" in the results of these trials can be explained by the fact that em barking on a strategy (such as a special diet) which successfully reduces your cholesterol level will be substantially m ore likely to prevent a heart attack if you are 45 than if you are 85. This, essentially, is the basis of the grievance of Professor H ans Eysenck, who has constructed a vigorous and entertaining critique of the science of m etaanalysis. Eysenck’s reservations about m etaanalysis are borne out in the infam ously discredited m etaanalysis which dem onstrated (wrongly) that there was significant benefit to be had from giving intravenous m agnesium to heart attack victim s. A subsequent m egatrial involving 58000 patients (ISIS-4) failed to find any benefit whatsoever and the m etaanalysts’ m isleading conclusions were subsequently explained in term s of publication bias, m ethodological weaknesses in the sm aller trials, and clinical heterogeneity. As one who tends to side with the splitters, I would put Eysenck’s m isgivings about m etaanalysis high on the list of 135 H OW TO READ A PAPER required reading for the aspiring system atic reviewer. Indeed, I recently threw m y own hat into the ring when Sim on G riffin published a m etaanalysis of prim ary studies into the m anagem ent of diabetes by prim ary health care team s. As I said in m y com m entary on his article, "Four apples and five oranges m akes four apples and five oranges, not nine appleoranges". Fortunately, the two of us have agreed to differ – and on a personal level we rem ain friends. For an authoritative review of the technicalities of integrating heterogeneous pieces of evidence into system atic reviews, see the article by Cindy M ulrow and colleagues. A com parison of results of m eta-analyses of random ised controlled trials and recom m endations of clinical experts. Secondary prevention following stroke or TIA in patients with non-rheum atic atrial fibrillation: anticoagulant therapy versus control. An em pirical study of the possible relation of treatm ent differences to quality scores in controlled random ized clinical trials. Assessing the quality of random ized controlled trials: current issues and future directions. The Cochrane Collaboration: preparing, m aintaining, and dissem inating system atic reviews of the effects of health care.

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The top number represents milligrams of carbidopa discount robaxin 500 mg visa muscle relaxant neck pain, and the bottom number represents milligrams of levodopa robaxin 500mg spasms compilation. Then he increased the dose slowly, so that after eight years I was taking three or four 10/100s per day, depending on my needs. Remember that you can always discuss your medication with your doctor and seek a second opinion from another doctor if you are concerned that you are being given too many pills, too soon. If someone does not respond at all to Sinemet, doctors investigate the possi- bility that the patient has a look-alike disease, rather than Parkin- medications and therapies 83 son’s. Sinemet controls the primary symptoms of Parkinson’s very well, except that in some people it does not control tremors effectively. If you have a tremor that is interfering with your work or daily life, you need to discuss with your doctor the possibility of your taking an additional medication to control it. Remember that Sinemet is best taken approximately forty-five to sixty minutes before meals. Observe the amount of time your Sinemet takes to kick in, and schedule that amount of time between taking your pill and eating your meal. Sinemet will work better if it is not competing with your food, and your meal will be more enjoyable when your medication is already working. Scientists believe that protein (in meat, fish, milk products, eggs, cheese, legumes, wheat products, and nuts) competes with Sinemet and reduces its effect. Doctors now advise people with Parkinson’s who take Sinemet and who experience troubling fluc- tuations to avoid protein during the day (breakfast and lunch), when they need their strength, and to take the whole day’s protein requirement at the evening meal. The doctor may have to modify the dosage of Sinemet after the start of the low-protein diet. The diet should be designed by a dietitian who is familiar with the needs of the person with Parkinson’s and with how to fit nutritional require- ments into a very different eating pattern. Patients who are diabetic, seriously underweight, or recovering from surgery or lacerations should not attempt this diet. Parkinson’s patients continue to respond to Sinemet for a varying number of years, some people for many years and others for fewer. One of the biggest problems is that over time, this drug becomes less effective for the patient, so that larger and larger doses are given. Dyskinesias are large involuntary movements, such as writhing, twisting, jerking, smacking of the lips, or bobbing of the head, all of which are very different from the fine tremors of the disease itself. Another side effect, dystonia, is the abnormal posturing of an extremity (a hand or a foot). A very bothersome side effect is the "on-off " effect, in which a person may experience sudden changes in mobility. For example, he may suddenly "freeze" in the middle of a step (which may cause him to fall). There are several ways to deal with the side effects that result from the long-term use of Sinemet and overmedication. One method that doctors use is to delay prescribing Sinemet for as long as possible. Another method is dividing the total daily dose of Sinemet into smaller, more frequent doses. During the drug holiday, the patient is hospitalized for several weeks, and under close supervision, the Sinemet is grad- ually withdrawn. Toward the end of the holiday, Sinemet is re- introduced but at a much lower dose. At the lower dose, the side effects are reduced or eliminated, while the Parkinson’s symptoms are controlled. Doctors have now learned to better manage the medication so that the person with Parkinson’s doesn’t become overmedicated. Because of better drug management, there is rarely, if ever, a need for the drug holiday. For patients who are already long-term users of Sinemet, a dopamine agonist—such as bromocriptine (Parlodel) or pergolide (Permax)—may be added to the drug regimen, which may permit the dose of Sinemet to be lowered and may help in other ways to alleviate the side effects. One of the newer dopamine agonists is ropinirole (Requip), a medication that is used in treatment before levodopa is prescribed, medications and therapies 85 as well as along with it. By 2001, many neurologists were using dopamine agonists as a first drug for people with early Parkinson’s, according to information published in the journal Neurology. Studies have shown that ropinirole can be used as a very effec- tive treatment before doctors resort to prescribing levodopa; also, patients who take ropinirole may require less levodopa.

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WHY AND (PROVISIONALLY) HOW DISEASE IS A RADIAL CATEGORY The "disease" category begins at the level of symptoms generic robaxin 500 mg otc muscle relaxant use, basic components of disease entities 500mg robaxin fast delivery spasms on right side of stomach. It is apparent on first inquiry, although detailed empirical confirmation is needed, that the symptom, such as a "cut," a "bloody nose," a "headache," "blindness," "numbness," "vomiting" or "fever" is the level on which most of us would start to understand the whole system of concepts topped by "disease in general. In George Lakoff’s terms, embodied symptoms are "directly under- stood" whereas the understanding of disease as an underlying unified pattern of symptoms is indirect. Although the capacity to have symptoms is certainly healthy, within limits, the actual presence of them is not in most instances. If disease were entirely a social construction HEALTH AND DISEASE 55 there should be cultures that would embrace chest pain, headaches, arthralgias, sore throats and rashes as healthy. Any author denying that symptoms provide an experiential, cross-cultural foundation for disease ought to produce such examples for our edification. Having said that much about the most basic symptoms, there are some experi- ences which can be considered symptoms to a varying degree, and in some contexts these are not even thought of as symptoms. For example, shortness of breath, fatigue, anxiety, depression, forgetfulness and itching are almost always experiences we would rather get over, but the mere fact that they are generally unpleasant does not turn them into basic constituents of disease any more than unpleasantness renders hunger or homesickness pathological. Factors like the age of a person experiencing these discomforts, the reason for and nature of their onset as well as their intensity determine whether they are considered out of place. It is when they are wrong for the circumstances that they become symptoms, and then they function just like symptoms of the more incontrovertible type, i. They have other cognitive features which structure the symptoms, locate them in a context and assign them a history as well as meaningful implications. Although symptoms are the groundwork, a much larger semantic architecture is built on them. Notions of etiology, nature of onset, patterns of progression, symptom clusters, signs, pathophysiology, epidemi- ology and prognosis also constitute diseases. For this reason, symptoms are not diseases by themselves, and prototypical members of the "disease" category, such as pneumonia, are not at the most basic level in the cognition of illness. Individual diseases are instead complexes of features like those just mentioned, among which the symptoms are at the basic level. Whereas it is "self-evident" whether someone has a cough, a runny nose and a fever it is not automatically evident on the surface whether the person has a cold, influenza, whooping cough or pneumonia. In the case of a classical category, all members have essential defining features plus added features which differentiate them one from another. In contrast, the members of the "disease" category are generated from their connection to central members but do not have even all of the main features of these central members. In addition, an abstractionist analysis of the "disease" category will not work because any skeletal features which could be asserted to apply in common to all the varying members (i. Their number is always fluctuating and controversial, because of conflicting and evolving 56 CHAPTER 2 principles for lumping and splitting and disputes about the relative significance of "natural kinds" versus "social constructs. The cluster of ideal cognitive models is generated from the bottom up, starting with our experience of symptoms and what we have found out about their causes and cures. Beginning with symptoms, understanding builds up to individual disease concepts and their sub-categorical variants, then the classes of disease, like infectious diseases and vascular diseases, and at last, disease in general. The broader categories are understood in terms of the more specific ones, by and large. As we have already seen, there is no classical criterion, no univocal set of necessary and sufficient features to define disease literally. Depending on the vagaries of ongoing research, academic fashion and the mutually contradictory pronouncements of authorities at different times and in different places, category assignments shift, drift and are often in dispute. There is very little about this whole system which accords well with classical category structure. Central members of this category are extended by cognitive proximity, analogy and metaphor to increas- ingly peripheral examples. If a history of disease identifications were undertaken, I suspect that the central prototypes would be found to have been the first ones labeled as "diseases. Analogies and metaphors act cognitively like forces (such as gravity) or links in that the easily identified, clear cut central members present a cognitive pull on marginal examples, drawing them into association. At the very margins of the general "disease" category the most peripheral examples wobble in their orbits, so to speak, partially gravitating toward other large categories in the lexical neighborhood of disease: "old age," "weakness," "crime," "harm," "suffering," "eccentricity" and "infertility. Some rhetorical arguments try to reposition members of categories toward either their centers or their margins.

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