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By B. Sigmor. Glenville State College.

Examples are reminding systems that continuously screen patient data for conditions that should be brought to the clinician’s attention (for example the patient’s kidney function is decreasing order himplasia 30 caps with visa greenwood herbals, or the patient is eligible for preventive screening) himplasia 30caps cheap herbs pool. Other systems, such as critiquing systems, may monitor the decisions of the clinician and report deviations from guidelines. Although hundreds of clinical decision support systems have been reported in the literature, only a few have been the subject of a rigorous clinical evaluation. Of those that have been evaluated, however, the majority of the studies showed an impact on clinician performance. In light of the currently available evidence, clinical decision support systems constitute a possible method to support the implementation of clinical guidelines in practice. Observational databases As a result of the increased use of electronic medical records, large observational databases containing data on millions of patients have 172 DIAGNOSTIC DECISION SUPPORT become available for researchers. The data contained in these databases is not of the same quality as the data collected in, for example, a clinical trial. They are collected in routine practice, and, although most observational databases attempt to standardise the recording of data and to monitor their quality, only a few observational databases require the clinician to record additional information. The advantage of observational databases, however, is that they reflect current clinical practice. Moreover, the data are readily available and the costs are not prohibitive. In settings where all the medical data are recorded electronically, the opportunities for research are similar to studies carried out using paper charts. Compared to paper charts, these observational databases provide an environment where the analysis can be performed faster, the data are legible, “normal” practice can be studied, rare events can be studied, longitudinal follow up of patients is possible, and subgroups for further study (such as additional data collection, or patients eligible for prospective trails) can be identified. In cases where a rapid analysis is required (for example a suspected side effect of a drug), observational databases provide a setting for a quick assessment of the question. Researchers in medical informatics use these observational databases to assess the behaviour of a decision support system prior to introducing that system into clinical practice. Such an analysis allows the researchers to determine, for example, the frequency of advice (for example the frequency of reminders) and to study the trade off between false positive and false negative alerts. When the clinical decision support system relies on a model that uses patient data to train that model, observational databases allow the tuning of that model to the population in which it will be used. Observational databases that rely on electronic records have limitations. Analysis of the contents of the records shows that information important for a researcher is often not recorded. Medical records typically contain data describing the patient’s state (for example the results of laboratory tests) and the actions of the clinician (such as prescribing medication). A further complicating factor is that when data in the medical record describe the relationship between observations (or findings) and actions (for example treatment), the information is often recorded in the form of free text. The clinician’s first and most important objective in keeping automated medical records is to document with the purpose of ensuring the quality and continuity of medical care. From the clinician’s perspective, free text is often an ideal method for expressing the patient’s condition. Researchers, on the other 173 THE EVIDENCE BASE OF CLINICAL DIAGNOSIS hand, prefer coded data to facilitate the automatic processing of large numbers of patients. It is unrealistic, however, to expect clinicians to code all relevant data: the time required to do so would render it impractical. In addition, coding is in essence a process of reducing the rich presentation of the patient–doctor encounter to a limited set of predefined terms. The data available in an observational database may therefore not be sufficient to answer a specific research question validly. The completeness of data can only be discussed in the context of a specific study. It is not possible to predict all possible data that would be required for all possible studies. Depending on the study question and the impact of incomplete information, additional data may need to be collected. Confounding by indication To illustrate the caveats when analysing observational databases, we discuss the problem of confounding by indication. In essence, confounding by indication is often “confounding by diagnosis”, since diagnostic assessment is the starting point for any treatment. As an example we will use an observational database used by Dutch GPs: the so-called IPCI database.

However best 30 caps himplasia kairali herbals, fat-suppressed T2-weight- CT scanning can show cortical destruction and marrow ed images have the added advantage of showing reactive edema earlier than radiographs discount 30caps himplasia with mastercard herbs native to outland, MRI and nuclear medi- marrow edema in the subjacent bone (analogous to the cine studies are typically the first-line studies. MR im- subchondral uptake seen on bone scans), which is often a ages show the marrow edema pattern, but to increase the clue to the presence of small chondral defects in the over- specificity, osetomyelitis should only be diagnosed when lying joint surface. Magnetic resonance imaging, with or without intraartic- Both benign and malignant bone tumors occur com- ular or intravenous contrast, is the imaging study of monly around the knee. Radiographs should be the initial choice for most soft-tissue conditions in and around the study in these patients, and are essential for predicting the knee. Ultrasound can also be used in selected circum- biologic behavior of the tumor (by analysis of the zone of stances for relatively superficial structures. The intraosseous extent of Fibrocartilage tumor and the presence and type of matrix are easiest to determine with CT examination. For staging beyond the The fibrocartilagenous menisci distribute the load of the bone (to the surrounding soft tissues, skip lesions in oth- femur on the tibia, and function as shock absorbers. In the future, The first is intrameniscal signal on a short-TE (T1- PET scanning may be used to stage some bone tumors as weighted, proton-density-weighted, or gradient-recalled) well. Additionally, MRI is at least as sensitive as bone image that unequivocally contacts an articular surface of scintigraphy for detecting metastases, and at least as sen- the meniscus. Intrameniscal signal that only possibly sitive as radiography in patients with multiple myeloma, touches the meniscal surface is no more likely torn than 30 D. On MR images, the appear- second criterion is abnormal meniscal shape. In ance is that of high-signal intensity amorphous material cross-section, the normal meniscus is triangular or bow- between the intact ligament fibers on T2-weighted im- tie shaped, with a sharp inner margin. The ligament may appear enlarged in cross- the normal shape – other than a discoid meniscus or one section, and often there are associated intraosseous cysts that has undergone partial meniscectomy – represents a formed near the ligament attachment points. These properties include the lo- cation of the tear (medial or lateral, horns or body, pe- Muscles and Tendons riphery or inner margin), the shape of the tear (longitudi- nal, horizontal, radial, or complex), the approximate The muscles around the knee are susceptible to direct and length of the tear, the completeness of the tear (whether indirect injuries. Blunt trauma to a muscle results in a it extends partly or completely through the meniscus), contusion. On T2-weighted or STIR MR images, contu- and the presence or absence of an associated meniscal sions appear as high-signal-intensity edema spreading cyst. The radiologist should also note the presence of dis- out from the point of contact in the muscle belly. MRI, these appear as regions of edema centered at the A meniscal tear that heals spontaneously or following myotendonous junction, with partial or complete disrup- repair will often still contain intrameniscal signal on tion of the tendon from the muscle in more severe cases short-TE images that contacts the meniscal surface. Around the knee, muscle trauma affects the distal When the abnormality is also present on a T2-weighted hamstrings, distal quadriceps, proximal gastrocnemius, image, when there is a displaced fragment, or when a tear soleus, popliteus, and plantaris muscles. Tendonopathy can be painful or asymp- none of these features is present, MRI or CT examination tomatic; but most importantly, tendonopathy weakens after direct arthrography is useful. The patellar, examination, the presence of injected contrast within the quadriceps, and semimembranosus tendons are most fre- substance of a repaired meniscus is diagnostic of a quently involved around the knee. Sonographically, a degen- a partial meniscectomy; in these cases both the meniscal erated tendon appears enlarged, with loss of the normal shape and internal signal are unreliable signs of recurrent parallel fiber architecture, and often with focal hypoe- meniscal tear. A gap between the tendon noninvasive test for recurrent meniscal tears following fibers indicates that the process has progressed to partial partial meniscectomy. Similarly, on MR images, focal or dif- fuse enlargement of a tendon with loss of its sharp mar- Ligaments gins indicates tendonopathy. In those cases in which T2-weighted images show a focus of high signal intensi- T2-weighted images demonstrate ruptures of the cruciate, ty, surgical excision of the abnormal focus can hasten collateral, and patellar ligaments. Partial or complete dis- cross-sectional images are important to examine. The di- ruption of tendon fibers represents a tendon tear on MRI rect sign of a ligament tear is partial or complete disrup-. When macroscopic tearing is present, the radiolo- tion of the ligament fibers. While edema surround- gist should also examine the corresponding muscle belly ing a ligament is typically seen in acute tears, edema sur- for fatty atrophy (which indicates chronicity) or edema rounding an intact ligament is a nonspecific finding, (suggesting a more acute rupture). If the tear is complete, which can be seen in bursitis or other soft tissue injuries, the retracted stump should be located on the images as in addition to ligament tears.

Neurogenic causes include autonomic dys- drugs cheap himplasia 30 caps with visa herbals summit, large meals) himplasia 30caps on line klaron herbals, volume expansion (using salt supple- function or failure, which can occur in association with other ments and/or medications with salt-retaining/volume-ex- central nervous system abnormalities, such as Parkinson’s panding properties), and mechanical measures (including disease, or may be secondary to systemic diseases that can tight-fitting elastic compression stockings or pantyhose to damage the autonomic nerves, such as diabetes or amyloi- prevent the blood from pooling in the veins of the legs dosis; vasovagal hyperactivity; hypersensitivity of the upon standing). Unfortunately, even when these measures carotid sinus; and drugs with sympathetic stimulating or are employed, some patients continue to have severe, de- blocking properties. Nonneurogenic causes of hypotension bilitating effects from hypotension. A more powerful activation of the barorecep- In fact, mean arterial pressure may be increased slightly tor reflex, as occurs during severe hemorrhage is required to above the recumbent value. However, two other How is increased sympathetic nerve activity maintained if mechanisms return blood from the legs to the central blood the mean arterial pressure reaches a value near or above that volume. If the leg muscles periodically contract sympathetic nerve activity return to recumbent levels if the while an individual is standing, venous return is increased. There Muscles swell as they shorten, and this compresses adjacent are two reasons. Because of the venous valves in the limbs, the blood turns to the same level (or even higher), pulse pressure re- in the compressed veins can flow only toward the heart. As indicated earlier, the fir- provides an effective pump that transiently increases ve- ing rate of the baroreceptors depends on both mean arterial nous return relative to cardiac output. Reduced pulse pressure means the shifts blood volume from the legs to the central blood vol- baroreceptor firing rate is reduced even if the mean arterial ume, and end-diastolic volume is increased. Second, although mean arterial ercise, such as walking, returns the central blood volume pressure is returned to the recumbent value, central blood and stroke volume to recumbent values (Fig. Consequently, the cardiopulmonary re- The respiratory pump is the other mechanism that acts ceptors continue to discharge at a lower rate, leading to in- to enhance venous return and restore central blood volume creased sympathetic activity. Quiet standing for 5 to 10 minutes invariably the decreased stretch of the cardiopulmonary receptors that leads to sighing. This exaggerated respiratory movement provides the primary steady state afferent information for the lowers intrathoracic pressure more than usually occurs with reflex cardiovascular response to standing. The fall in intrathoracic pressure raises the The heart and brain do not participate in the arteriolar transmural pressure of the intrathoracic vessels, causing constriction caused by increased sympathetic nerve activity these vessels to expand. Contraction of the diaphragm si- during standing; therefore, the blood flow and supply of oxy- multaneously raises intraabdominal pressure, which com- gen and nutrients to these two vital organs are maintained. Because the venous valves pre- vent the backflow of blood into the legs, the raised intraabdominal pressure forces blood toward the intratho- Muscle and Respiratory Pumps Help racic vessels (which are expanding because of the lowered Maintain Central Blood Volume intrathoracic pressure). The seesaw action of the respiratory Although standing would appear to be a perfect situation pump tends to displace extrathoracic blood volume toward for increased venoconstriction (which could return some of the chest and raise right atrial pressure and stroke volume. During Just after contraction contraction Just before contraction 90 mm Hg added hydrostatic pressure Artery Vein Arterial pressure Venous pressure 90 + 93 mm Hg 90 + 10 mm Hg 90 + 93 mm Hg 20 + 10 mm Hg FIGURE 18. This mechanism increases ve- static column of blood, lowering venous (and capillary) hydro- nous return and decreases venous volume. Inspiration leads to an (mL) increase in venous return and stroke volume. The decline in arterial pres- sure is caused by a steady loss of plasma volume, as fluid fil- ters out of capillaries of the legs. The center section shows the effects of a shift from the prone to the upright position with quiet standing. The right panel shows the effect of activating the muscle pump by contracting leg muscles. Note that the muscle pump restores central blood volume and cardiac output to the levels in the prone position. The fall in heart rate and rise in peripheral blood flow (forearm, splanchnic, and renal) associated with activation of the muscle pump reflect the reduction in baroreceptor reflex activity associated with increased cardiac output. RVEDP, right ventricular end-diastolic pressure; SVR, systemic vascular resistance. Small type represents compensatory changes that return variables toward the original values.

Carbonic anhydrase catalyzes the for- failure of the liver to secrete VLDLs buy cheap himplasia 30caps on line herbs under turkey skin, or failure to se- mation of carbonic acid from carbon dioxide and wa- crete a bicarbonate-rich pancreatic juice himplasia 30caps low cost herbal. Lactase hydrolyzes lactose to form ide from carbon and oxygen, bicarbonate ion from both glucose and galactose. None of the other combi- carbonic acid, hydrochloric acid, or hypochlorous nations is correct. Because maltose does not contain galactose or the release of kallikrein by the salivary acinar cells, fructose, none of the other choices is correct. Kinins include taken up by enterocytes through a sodium-dependent bradykinin and lysyl-bradykinin. Xylose and sucrose are not taken up by en- leases amino acids from the amino end of peptides and terocytes. Intrinsic factor is secreted by the The hydrolysis of phosphatidylcholine, not triglyc- parietal cells of the stomach and is not secreted by the eride, results in the formation of lysophosphatidyl- salivary glands. Although diglyceride is an intermediate in the ramidase are found in saliva. In the fasting state, the pH of the drolysis continues until 2-monoglyceride and fatty stomach is low, between 1 and 2. Salivary secretion is inhibited by at- triglyceride totally to form glycerol and fatty acids. The small intestine transports dietary petitively inhibits ACh at postganglionic sites, inhibit- triglyceride as chylomicrons in lymph. Aspirin is the most widely used analgesic (pain pathway for the transport of dietary lipids to the circu- reducer), antipyretic (fever reducer), and anti-inflam- lation by the small intestine. Omeprazole inhibits the H /K -ATPase crete LDLs, and although it does secrete HDLs, they and, thus, inhibits acid secretion. The chief cells of the stomach secrete to the blood by the small intestine. Amino acids, as well as dipeptides crete hydrochloric acid and intrinsic factor. Gastrin and tripeptides, use different brush border transporters and CCK are secreted by specialized endocrine cells. Histamine interacts with its receptor taken up passively by any part of the GI tract. Dietary protein is transported in the tamine does not cause an increase in intracellular portal blood as free amino acids. Although dipeptides sodium or cGMP or a decrease in intracellular calcium. When the pH of the stomach falls hydrolyzed by the brush border membrane, as well as below 3, the antrum secretes somatostatin, which acts by cytoplasmic peptidase to form free amino acids. Enterogastrones are Vitamins A, D, E, and K are all fat-soluble vitamins. Intrinsic factor is involved rect role in the absorption of calcium by the GI tract. Vitamin A is transported in chylomi- acidic chyme and is responsible for stimulating pancre- crons as ester. Vitamins D, E, and K are transported in APPENDIX A Answers to Review Questions 727 the free form associated with chylomicrons. Vitamin correct because the pancreas does not produce more B12,a water-soluble vitamin, is transported in the blood glucagon in portacaval shunt patients. The other choices do not apply to the ab- not nearly as important as the liver in removing sorption of potassium by the small intestine. Ascorbic acid enhances iron absorp- because the small intestine does not produce glucagon. Ascorbic acid does not enhance heme intestine is not compromised in portacaval shunt pa- iron absorption, nor does it affect heme oxygenase ac- tients. Hemosiderin is an intracellular com- Chapter 28 plex of ferric hydroxide, polysaccharides, and proteins. Alcohol dehydrogenase catalyzes the Ceruloplasmin is a circulating plasma protein involved conversion of alcohol to acetaldehyde, which is then in the transport of copper.

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