By K. Ernesto. Nyack College.

Groupware like Lotus Notes has long made it possible for clinical and research teams that are dispersed geograph- ically to work on common projects 160mg valsartan with mastercard. Physicians’ natural curiosity and gregariousness seem likely to find new outlets in virtual collab- oration on the Internet buy valsartan 40 mg with mastercard. Medical journals have raced to make their content available to physicians and other subscribers online discount valsartan 40mg without a prescription. When physicians subscribe to their service, which is called Cog- niQ, they list all of the medical journals they follow. Physicians can scan the new articles and choose those of interest to be archived in their box on the Unbound Medicine server, in abstract or full-text form. Physicians 83 Thus, questions that would have been lost end up getting an- swered and stored in an easily retrievable fashion. Over time, the server retains the entire stream of answers to questions and relevant journal articles as a personalized “knowledge archive,” making it unnecessary for the physician to retain the new knowledge in his or her memory. This service will evolve from being modem dependent to being wireless as it becomes more widely available. As this occurs, physicians will be freed from the need to return telephone calls or to give verbal orders, enabling them to practice medicine “anytime, anywhere. In many institutions, physician mistrust of hospital motivations and strategies is a dominant theme. Mistrust Although competitive tensions between physician-sponsored enter- prises and hospitals have contributed to this problem, many physi- cians view the hospital as a battleship whose wake is sufficient to swamp the small boats it operates. The fact that hospitals and physi- cians have completely separate information domains complicates the ability to implement new clinical information systems. The Hospital as Potential Information Source Hospitals are presently committing major capital resources to com- puterize both operations and clinical services. As argued above, physician practices, even many large groups, are capital poor and thus lag in automating their processes and services. It is entirely possible given the present course that hospitals will complete this Physicians 85 process a decade or more ahead of physicians, leaving what physi- cians “know” about their patients locked up in paper records and their memories. When physicians do automate, if no compatibility standards are set in advance, they will use incompatible software and be unable to move clinical information between their systems and those of the hospital. Optimal patient care would require that the clinical team be able to access important clinical information about a patient at any place and at any time. Because hospitals have capital, and physicians, generally speaking, do not, hospitals could be a potential source for modern digital clinical information systems, as well as patient care support tools like disease management, for their physicians. If hospitals could help bring about a shared record format across their medical staffs, it would be easier for physicians to send patient information to one another for consultative purposes. Historically, physicians have been extremely reluctant to permit hospitals access to their private practices. Many experiments by hos- pitals during the 1990s with salaried employment of physicians and with practice management support ended in costly failure. Physi- cians resisted installing inexpensive software that enabled them to perform remote order entry or retrieval of test results from hospi- tals because they thought it opened a portal that enabled hospital executives to understand their practice’s economics. Legal and Regulatory Barriers Besides the mistrust discussed above, legal and regulatory barriers make linking hospitals and physicians difficult. Federal Medicare regulations forbid hospitals from offering physicians anything of value (including software and services) if it would influence their patterns of hospital utilization. These statutes were intended to pre- vent hospitals from, in effect, bribing physicians to bring their pa- tients in. If compatible clinical software made it easier for physicians 86 Digital Medicine with a choice to use the facility that provided them the software, it might trigger fraud and abuse investigations. Tax laws provide another barrier to the sharing of clinical soft- ware between hospitals and physicians. The Internal Revenue Code and state laws forbid not-for-profit hospitals (recall that 85 percent of all community hospitals are not-for-profit) from giving physicians (or anyone else) anything of value. Competitive advantage for specific providers could be eliminated by regulation that requires clinical information systems developed by different vendors to interoper- ate (that is, to use common record formats, coding conventions, messaging standards, etc. This would mean that, once installed, physicians could use their clinical software in conjunction with any of the available local hospitals or retrieve information about their patients from any of them. The fact that software and services could be provided on a dial- in basis without significant capital expenditures by hospitals on the physicians’ behalf could help change some of the equation as well. The most expensive part of a physician office’s digital conversion is transferring all of its existing patient records to digital form so they can be used by the information system. If these costs can be surmounted and physicians can obtain password-protected access to computerized patient records and clinical decision support from their offices, it would be a major boost to overall computerization. Hospitals and Physicians Digitizing Patient Records Together Ideally, hospitals and physicians should move together to digitize patient records.

As intakes of the target amino acid approach the requirement level by increasing the intake of the limiting amino acid buy valsartan 40mg on-line, the plasma level of the amino acid starts to increase progressively (see Figure 10-4) order 40 mg valsartan visa. The point at which the “constant” portion of the relationship between intake and plasma concen- tration intersects the linear portion is considered to be an estimate of the requirement generic valsartan 80 mg on line. A variation on this method involves the examination of the changes in the plasma concentration of the test amino acid as the adult moves from the post absorptive to the fed state post-consumption (Longnecker and Hause, 1961). The main difficulty is that amino acid metabolism is so complex that factors other than the level of amino acid intake, such as gastric emptying time, can influence its concentration (Munro, 1970). Furthermore, the relationship between the intake of the amino acid and its circulating concentration is not necessarily bilinear, so it is difficult to determine a “breakpoint” (Young et al. Although in some regards this problem applies also to the oxidation methods discussed below, over the last 20 years these later methods have supplanted plasma amino acid concentration–based approaches. This marked a major theoretical advance over the nitrogen balance and plasma amino acid response methods. Thus by analogy to the 2 concentration method, it is assumed that below the requirement the test amino acid is conserved and that there is a low constant oxidation rate, but once the requirement is reached, the oxidation of the test amino acid increases progressively. The most salient problem arises from the reliance on the determination of a breakpoint in the oxidation of the test amino acid. However, at these low dietary intakes, the intake of the infused labeled amino acid becomes significant in relation to dietary intake. This limits its use largely to the branched chain amino acids, phenylalanine, and lysine. Other amino acids, such as threonine and tryptophan, pose particular problems (Zhao et al. A criticism of this method has been that measurements were only made during a short period during which food was given at regular hourly intervals. A later modification of this approach was to infuse the labeled amino acid during a period of fasting followed by a period of hourly meals, thus acknowledging the discontinuous way in which food is normally taken (Young et al. However, although this was an advance on the earlier approach, assumptions still had to be made to extrapolate the results from the short periods to a full day. Thus the 24-hour amino acid balance method was developed to determine the balance of the test amino acid over a 24-hour period that encompassed periods of fasting and feeding. This marked a significant advance in deter- mining amino acid requirements because it moved investigations away from the simple study of nitrogen metabolism and allowed, in principle at least, direct measurements of the quantities of the amino acid lost under different nutritional circumstances. The first limitation arises from the unresolved questions related to the method’s theoretical basis. This is difficult because amino acid metabolism is compartmentalized and measurements of plasma amino acid labeling likely underestimate true turnover, and hence true oxidative loss, of the amino acid. Although for some amino acids this problem can be circumvented by administering a labeled metabolic product of the amino acid (e. The second drawback is practical—measuring the oxidation of the test amino acid over a complete 24-hour period makes the method labor intensive. This probably underlies the fact that to date this method has been applied to only three amino acids: leucine (El-Khoury et al. The reasoning is that when a single indispensable amino acid is provided below its requirement, it acts as the single and primary limitation to the ability to retain other nonlimiting amino acids in body protein. These other amino acids, including the indicator amino acid, are then in nutritional excess and are oxidized (Zello et al. As the intake of the test amino acid is increased, protein retention increases and the oxidation of the indicator amino acid falls until the requirement level of the test amino acid is reached, after which the oxidation of the indicator amino acid is lower and essentially constant. The data are then analyzed to obtain as estimate of the intersection of the constant and linear portions of the relationship (the breakpoint). The first advantage is that the metabolic restrictions of carbon dioxide release apply only to the indicator amino acid. Second, the pool size of the indicator amino acid does not change radically as the intake of the test amino acid is varied. Thus to some extent, potential problems of compart- mentation are minimized and, in principle, the method does not require estimates of the turnover of the indicator amino acid. Second, the dependence of the result on the amount of total protein given during the isotope infusion has not been established. Third, the choice of the best indicator is still under study so that data obtained with the method are dependent on the assumption of the general applica- bility of the indicator amino acids (phenylalanine and lysine) that have been used most frequently. Classical nitrogen balance studies in humans show that it takes 7 to 10 days for urinary nitrogen to equilibrate in adults put on a protein-free diet (Rand et al. On the other hand, it has been shown that most (about 90 percent) of the adaptation in leucine kinetics is complete in 24 hours (Motil et al.

Later in life order 160mg valsartan visa, risk of certain diseases may be altered by arachidonic acid and arachidonic acid-derived eicosanoids purchase valsartan 80mg visa. Consequently trusted valsartan 160 mg, the desirable range of n-6:n-3 fatty acids may differ with life stage. Similarly, stable isotope studies have shown that increased intakes of α-linolenic acid result in decreased conversion of linoleic acid to its metabolites, and the amounts metabolized to longer- chain metabolites is inversely related to the amount oxidized (Vermunt et al. These eicosanoids have been shown to have beneficial and adverse effects in the onset of platelet aggregation, hemodynamics, and coronary vascular tone. More recent, large clinical trials with infants fed formulas providing linoleic acid:α-linolenic acid ratios of 5:1 to 10:1 found no evidence of reduced growth or other problems that could be attributed to decreased arachidonic acid concentrations (Auestad et al. Clark and coworkers (1992) con- cluded that intake ratios less than 4:1 were likely to result in fatty acid profiles markedly different from those from infants fed human milk. Based on the limited studies, the linoleic acid:α-linolenic acid or total n-3:n-6 fatty acids ratios of 5:1 to 10:1, 5:1 to 15:1, and 6:1 to 16:1 have been recommended for infant formulas (Aggett et al. In adult rats it has been determined that a linoleic acid:α-linolenic acid ratio of 8:1 was optimal in maintaining normal-tissue fatty acid con- centrations (Bourre et al. Increasing the intake of linoleic acid from 15 to 30 g/d, with an increase in the linoleic:α-linolenic acid ratio from 8:1 to 30:1, resulted in a 40 to 54 percent decreased conversion of linoleic acid and α-linolenic acid to their metabolites in healthy men (Emken et al. For example, low rates of heart disease in Japan, compared with the United States, have been attrib- uted in part to a total n-6:n-3 fatty acid ratio of 4:1 (Lands et al. Similarly, an inverse association between the dietary total n-6:n-3 fatty acid ratio and cardiovascular disease, cancer, and all-cause mortality (Dolecek and Grandits, 1991), as well as between fish intake and coronary heart disease mortality (Kromhout et al. In other studies, however, no differences were found in coronary heart disease risk factors when a diet containing a total n-6:n-3 ratio of 4:1 compared to 1:1 was consumed (Ezaki et al. Hu and coworkers (1999b) observed a weak relationship between the n-6:n-3 ratio and fatal ischemic heart disease since both α-linolenic acid and linoleic acid were inversely related to risk. Desaturation and elongation of trans linoleic and α-linolenic acid isomers containing a double bond at the cis-12 and cis-15 position, respectively, with formation of 20 and 22 carbon chain metabolites that could be incorporated into mem-brane lipids, have also been suggested. In vitro studies and studies with animals fed diets high in trans fatty acids have found evidence of reduced essential n-6 and n-3 fatty acid desaturation (Cook, 1981; Rosenthal and Doloresco, 1984). Studies in term infants found no relation between trans fatty acids and length of gestation, birth weight, or birth length (Elias and Innis, 2001). Similarly, an inverse asso- ciation between plasma phospholipid trans fatty acids and arachidonic acid has been found for children aged 1 to 15 years (Decsi and Koletzko, 1995). The industrial hydrogenation of vegetable oils results in destruction of cis essential n-6 and n-3 fatty acids and the formation of trans fatty acids (Valenzuela and Morgado, 1999). It is not clear if differences in dietary intakes of n-6 and n-3 fatty acids, rather than inhibition of linoleic acid and α-linolenic acid desaturation by trans fatty acids, explains the statistical inverse associations between trans and n-6 and n-3 fatty acids reported in some studies (Craig-Schmidt, 2001). Based on the much greater affinity of the ∆6 desaturase for cis n-6 and n-3 fatty acids than monounsaturated fatty acids (Brenner, 1974; Castuma et al. Fat is the major single source of energy in the diet of infants exclusively fed human milk. The high intake of fat and the energy density that it provides to the diet are important in providing the energy needed for rapid growth during early infancy. Table 8-2 shows the concentration and proportion of energy from fat provided by mature human milk from women delivering at term gestation. The mean energy content of mature human milk is 650 kcal/L (Chapter 5), thus dietary fat represents 55 percent of total energy intake for infants 0 through 6 months of age. Fomon and coworkers (1976) reported that the length and weight of infants were not different when fed formula and strained food providing 29 or 57 percent of energy from fat. Thus, an intake of 55 percent energy most likely exceeds the minimum percent needed for optimal growth of healthy infants. The proportion of energy from dietary fat decreases during the second 6 months of age when complementary foods, specifically infant cereals, vegetables, and fruits, are added to the diet of the infant. The average concentration of fat in milk is approximately 40 g/L during the second 6 months of lactation (Table 8-2). Therefore, the average fat intake from human milk and complementary foods would be 30 g/d ([0. Therefore, for infants 7 though 12 months of age, 40 percent of energy from fat is consumed from human milk and complementary foods. The most common sources of fat in infant formulas are soybean oil, safflower oil, sunflower oil, coconut oil, and palm oil. Children and Adolescents Ages 1 Through 18 Years A number of studies have been conducted to ascertain whether a cer- tain amount of fat is needed in the diet to provide normal growth in children. These data generally conclude that there is no effect of fat intake on growth when consumed at levels as low as 21 percent of energy and provided that the energy intake is adequate (Boulton and Magarey, 1995; Fomon et al. There is insufficient evidence to identify a defined intake level of fat to prevent obesity or chronic diseases. Adults Ages 19 Years and Older The amount of total energy as fat in the diet can vary from 10 to 50 percent without differing effects on short-term health (Jéquier, 1999). When men and women were fed isocaloric diets containing 20, 40, or 60 percent fat, there was no difference in total daily energy expenditure (Hill et al.

After setting up a list of possible diseases purchase valsartan 80mg free shipping, we can assign a pretest probabil- ity to each disease on the differential valsartan 160 mg visa. This is the estimated likelihood of disease in the particular patient before any testing is done order 40 mg valsartan amex. As we discussed earlier, it is based on the history and physical examination as well as on the prevalence of the disease in the population. This is the estimated likelihood of the disease in a patient after testing is done. A positive test tends to rule in the disease while a negative test tends to rule out the disease. However, the test can be an item of history, part of the physical examination, a laboratory test, a diagnostic x-ray, or any other diagnostic maneuver. Mathematically, the pretest probability of the disease is modified by the appli- cation of a diagnostic test to yield a post-test probability of the disease. Likelihood ratios are stable characteristics of a diagnostic test and give the strength of that test. The likelihood ratio can be used to revise dis- ease probabilities using a form of Bayes’ theorem (Fig. Before fully looking at likelihood ratios, it is useful to look at the definitions of normality in diagnostic tests. Typical results are yes or no, positive or negative, alive or dead, better or not. A common dichoto- mous result is x-ray results which are read as either normal or abnormal and showing a particular abnormality. There is also the middle ground, or gray zone, in these tests as sometimes they will be unreadable because of poor technical quality. In addition, there are many subtle gradations that can appear on an x-ray and lead to various readings, but they may not pertain to the disease for which the patient is being evaluated. The serum sodium level or the level of other blood components is an example of a con- tinuous test. A patient can have any of a theoretically infinite number of values for the test result. In real life, serum sodium can take any value from about 100 252 Essential Evidence-Based Medicine Fig. In practice, we often take continuous tests and select a set of values for the variable that will be con- sidered normal (135–145 mEq/dL for serum sodium) thereby turning this con- tinuous test into a dichotomous test, which is reported as normal or abnormal. Values of the serum sodium below 135 mEq/dL, called hyponatremia, or above 145 mEq/dL, called hypernatremia, are both abnormal. Definitions of a normal test result There are many mathematical ways to describe the results of a diagnostic test as normal or abnormal. In the method of percentiles, cutoffs are chosen at pre- set percentiles of the diagnostic test results. All values above the upper limit or below the lower limit of the normal percentiles are abnormal. Results are only specific to the population being studied and cannot be general- ized to other populations. One is for patients who are afflicted with the disease and the other is for those free of dis- ease. There is usually an overlap of the distributions of test values for the sick and not-sick populations. Some disease-free patients will have abnormal test results while some diseased patients will have normal results, thus setting any single value of the test as the cutoff between normal and abnormal will usually misclassify some patients. The ideal test, the gold standard, will have none of this overlap between diseased and non-diseased populations and will therefore be able to differentiate between them perfectly at all times. Ideally, when a research study of a diagnostic test is done, patients with and without the disease are all given both the diagnostic test and the gold-standard test. The results will show that some patients with a positive gold-standard test, and who have the disease, will have a positive diagnostic test and some will have a negative diagnostic test. The ones with a positive test are the true positives and those with a negative test are false negatives. A similar situation exists among patients who have a negative gold-standard test and therefore, are all actually disease-free. Some of them will have a negative diagnostic test result and are called true negatives and some will have a positive test result and are called false positives. Strength of a diagnostic test The results of a clinical study of a diagnostic test can determine the strength of the test. The ideal diagnostic test, the gold standard, will always discriminate dis- eased from non-diseased individuals in a population. The diagnostic test we are comparing to the gold standard is a test that is easier, cheaper, or safer than the gold standard, and we want to know its accuracy. That tells us how often it is correct, yielding either a true positive or true negative result and how often it is incorrect yielding either a false positive or false negative result. From the results of this type of study, we can create a 2 × 2 table that divides a real or hypothetical population into four groups depending on their disease 254 Essential Evidence-Based Medicine Fig.