By T. Karmok. Averett College.

Predictive values The probability that a patient with a particular outcome on a diagnostic test (positive or negative) has or does not have the disease generic 400 mg indinavir. Predictor variable The variable that is going to predict the presence or absence of disease generic 400mg indinavir overnight delivery, or results of a test buy 400 mg indinavir. Prevalence The proportion of people in a defined group who have a disease, condition, or injury. Prognosis The possible outcomes for a given disease and the length of time to those outcomes. Important in studies on therapy, prognosis, or harm, where retrospective studies make hidden biases more likely. Publication bias The possibility that studies with conflicting results (most often negative studies) are less likely to be published. Random selection or assignment Selection process of a sample of the population such that every subject in the population has an equal chance of being selected for each arm of the study. Randomization A technique that gives every patient an equal chance of winding up in any particular arm of a controlled clinical trial. Referral bias Patients entered into a study because they have been referred for a particular test or to a specialty provider. Relative risk The probability of outcome in the group with exposure divided by the probability of outcome in the group without the exposure. Reliability Loose synonym of precision, or the extent to which repeated measurements of the same phenomenon are consistent, reproducible, and dependable. Representativeness heuristic The ease with which a diagnosis is recalled depends on how closely the patient presentation fits the classical presentation of the disease. Research question (hypothesis) A question stating a general prediction of results which the researcher attempts to answer by conducting a study. Retrospective study Any study in which the outcomes have already occurred before the study and collection of data has begun. Risk Probability of an adverse event divided by all of the times one is exposed to that event. Risk factor Any aspect of an individual’s life, behavior, or inheritance that could affect (increase or decrease) the likelihood of an outcome (disease, condition, or injury. Rule out To effectively exclude a diagnosis by making the probability of that disease so low that it effectively is so unlikely to occur or would be considered non-existent. Sampling bias To select patients for study based on some criteria that could relate to the outcome. Sensitivity The ability of a test to identify patients who have disease when it is present. Sensitivity analysis An analytical procedure to determine how the results of a study would change if the input variables are changed. Setting The place in which the testing for a disease occurs, usually referring to level of care. Specificity The ability of a test to identify patients without the disease when it is negative. Spectrum In a diagnostic study, the range of clinical presentations and relevant disease advancement exhibited by the subjects included in the study. Spectrum bias The sensitivity of a test is higher in more severe or “well-developed” cases of a disease, and lower when patients present earlier in the course of disease, or when the disease is occult. Standard gamble A technique to determine patient values by which patients are given a choice between a known outcome and a hypothetical-probabilistic outcome. Stratified randomization A way of ensuring that the different groups in an experimental trial are balanced with respect to some important factors that could affect the outcome. Strategy of exhaustion Listing all possible diseases which a patient could have and running every diagnostic test available and necessary to exclude all diseases on that list until only one is left. Subjective Information from the patient, the history which the patient gives you and which they are experiencing. Surrogate marker An outcome variable that is associated with the outcome of interest, but changes in this marker are not necessarily a direct measure of changes in the clinical outcome of interest. Survival analysis A mathematical analysis of outcome after some kind of therapy in which patients are followed for given a period of time to determine what percentage are still alive or disease-free after that time. Systematic review A formal review of a focused clinical question based on a comprehensive search strategy and structured critical appraisal of all relevant studies. Testing threshold Probability of disease above which we should test before initiating treatment for that disease, and below which we should neither treat nor test. Threshold approach to decision making Determining values of pretest probability below which neither testing nor treatment should be done and above which treatment should be begun without further testing. Time trade-off A method of determining patient utility using a simple question of how much time in perfect health a patient would trade for a given amount of time in imperfect health. Treatment threshold Probability of disease above which we should initiate treatment without first doing the test for the disease. Triggering A thought process which is initiated by recognition of a set of signs and symptoms leading the clinician to think of a particular disease. Two-tailed statistical test Used when alternative hypothesis is non-directional and there is no specification of the direction of differences between the groups. Unadjusted life expectancy (life years) The number of years a person is expected to live based solely on their age at the time. Adjusting would consider lifestyle factors such as smoking, risk-taking, cholesterol, weight, etc. Uncertainty The inability to determine precisely what an outcome would be for a disease or diagnostic test. Validity (1) The degree to which the results of a study are likely to be true, believable and free of bias. Variable Something that can take on different values such as a diagnostic test, risk factor, treatment, outcome, or characteristic of a group. Yule–Simpson paradox A statistical paradox in which one group is superior overall while the other is superior for all of the subgroups. American National Standard for the Preparation of Scientific Papers for Written or Oral Presentation. The Evidence Based Medicine Workbook: Critical Appraisal for Clinical Problem Solving. Making Medical Decisions: an Approach to Clinical Decision Making for Practicing Physicians. Users’ Guides to the Medical Literature: a Manual for Evidence-Based Clinical Practice. Journal articles General Ad Hoc Working Group for Critical Appraisal of the Medical Literature. Quality of non- structured and structured abstracts of original research articles in the British Medical Journal, the Canadian Medical Association Journal and the Journal of the American Medical Association. Cause and effect Department of Clinical Epidemiology and Biostatistics, McMaster University Health Sci- ences Centre.

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During this situation cheap indinavir 400mg visa, protein break- down becomes a source of indispensable amino acid needs for synthesis of proteins critical to maintaining essential body function (Reeds et al buy generic indinavir 400mg. This labile protein reserve in humans is unlikely to account for more than about 1 percent of total body protein (Waterlow indinavir 400mg lowest price, 1969; Young et al. Thus, the immediately accessible stores of protein (which serve as the source of indispensable amino acids and amino nitrogen) cannot be considered in the same light as the huge energy stores in the form of body fat; the labile protein reserve is similar in weight to the glycogen store. The protein lost during fasting is functional body protein and thus there is no evidence for a protein reserve that serves only as a store to meet future needs. There is a wide range of variation in daily dietary protein intake, from the protein requirement and beyond, to which the body is able to adapt over a period of days, after which no further change in body protein con- tent occurs. However, pathological conditions, such as severe disease states, can cause substantial rates of protein loss due to the increased demand for either amino acids or carbon skeletons to meet local energy demands. If these conditions go unchecked for more than a few days, there may be a serious depletion of the body’s protein mass, which might eventually become life threatening. Although the evidence from short-term changes in diet suggests that the main loss of protein is from the viscera (de Blaauw et al. Although the free amino acids dissolved in the body fluids are only a very small proportion of the body’s total mass of amino acids, they are very important for the nutritional and metabolic control of the body’s proteins. The content of free and protein-bound amino acids in rat muscle is shown in Table 10-2. It can be seen that their ranges are considerable and that their concentrations in the free pool are in no way related to their concentrations in body proteins. In the human, free phenylalanine com- prises less than 2 percent of its total body pool, and corresponds to only about 1. Free glutamate and alanine comprise a larger proportion of their respective body pools, but they could not be considered as reserves for more than a very short time. In human muscle, glutamine has an exceptionally large free pool, containing about 10 to 15 g of nitrogen. After trauma, this pool can become depleted by more than 50 percent (Labow and Souba, 2000); its loss may then make a significant contribution to the total loss of nitrogen. Although the plasma compartment is most easily sampled, the concen- tration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids, such as leucine and phenylalanine, are essen- tially in equilibrium with the plasma. Others, notably glutamine, glutamic acid, and glycine, are 10- to 50-fold more concentrated in the intracellular pool. Dietary variations or pathological conditions can result in substantial changes in the concentrations of the individual free amino acids in both the plasma and tissue pools (Furst, 1989; Waterlow et al. Pathways of Amino Acid Metabolism The exchange between body protein and the free amino acid pool is illustrated by the highly simplified scheme shown in Figure 10-2. Similarly, there is a second pool, consisting of the free amino acids dis- solved in body fluids. The arrows into and out of the protein pool show the continual degradation and resynthesis of these macromolecules (i. The other major pathways that involve the free amino acid pool are the supply of amino acids by the gut from the absorbed amino acids derived from dietary proteins, the de novo synthesis in cells (includ- ing those of the gut, which are a source of dispensable amino acids), and the loss of amino acids by oxidation, excretion, or conversion to other metabolites. Amino Acid Utilization for Growth Dietary protein is not only needed for maintaining protein turnover and the synthesis of physiologically important products of amino acid metabolism but is, of course, laid down as new tissue. Studies in animals show that the composition of amino acids needed for growth is very simi- lar to the composition of body protein (Dewey et al. It is important to note, however, that the amino acid composition of human milk is not the same as that of body protein (Dewey et al. Maintenance Protein Needs Even when mammals consume no protein, nitrogen continues to be lost. Provided that the energy intake is adequate, these “basal” losses are closely related to body weight and basal metabolic rate (Castaneda et al. In man, normal growth is very slow and the dietary requirement to support growth is small in relation to maintenance needs except at very young ages. It follows that maintenance needs are of particular impor- tance to humans and account for a very large majority of lifetime needs for dietary protein. It has been known for decades (Said and Hegsted, 1970) that the body’s capacity to conserve individual amino acids at low intakes varies, so the pattern of amino acids needed in the diet to match their individual catabolic rates does not correspond precisely with the composition of body protein. This implies that there is very effective recycling of indispensable amino acids released continuously from protein degradation back into protein synthesis. Under conditions where the diet is devoid of protein, the efficiency of amino acid recycling is over 90 percent for both indis- pensable and dispensable amino acids (Neale and Waterlow, 1974). While highly efficient, some amino acids are recycled at different rates than others. Physiology of Absorption, Metabolism, and Excretion Protein Digestion and Absorption After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feed- ing. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bond- specific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. Thus, a significant portion (at least 50 percent) of fecal nitrogen losses represents the fixation by the colonic and cecal bacteria of nitrogenous substances (urea, ammonia, and protein secretions) that have been secreted into the intestinal lumen. Some authors have argued that the host-colon nitrogen cycle, by which nitrogenous compounds that diffuse into the gut are converted to ammonia by the microflora and are reabsorbed, is a regulated function and serves as a mechanism of nitrogen conservation (Jackson, 1989). The theoretical basis of this proposition has been partly confirmed by the recent demon- stration of the availability to the host of indispensable amino acids synthe- sized by intestinal microbes (Metges et al. However, not all investigators have obtained results indicative of regulated nitrogen cycling (Raguso et al. Although it seems clear that the efficiency of dietary protein digestion (in the sense of removal of amino acids from the small intestinal lumen) is high, there is now good evidence to show that nutritionally significant quantities of indispensable amino acids are metabolized by the tissues of the splanchnic bed, including the mucosal cells of the intestine (Fuller and Reeds, 1998). Thus, less than 100 percent of the amino acids removed from the intestinal lumen appear in the peripheral circulation, and the quantities that are metabolized by the splanchnic bed vary among the amino acids, with intestinal threonine metabolism being particularly high (Stoll et al. Currently, there is a lack of systematic information about the relationship between dietary amino acid intake and splanchnic metabolism, although there are indications that there is a nonlinear rela- tionship between amino acid intake and appearance in the peripheral blood (van der Schoor et al. Intestinal Protein Losses Protein secretion into the intestine continues even under conditions of protein-free feeding, and fecal nitrogen losses (i. Under this dietary circumstance, the amino acids secreted into the intestine as components of proteolytic enzymes and from sloughed mucosal cells are the only sources of amino acids for the maintenance of the intestinal bacterial biomass.