J. Eduardo Calonje, MD, DipRCPath

• Director of Diagnostic Dermatopathology, Department of Dermato-Histopathology, St John's Institute of Dermatology, St Thomas' Hospital, London, UK

Thus impotence yeast infection generic viagra extra dosage 150mg online, in plotting dose versus response over a wide range of doses problems with erectile dysfunction drugs buy 130 mg viagra extra dosage with mastercard, the effects of hormesis may also result in a "U-shaped" dose­response curve statistics of erectile dysfunction in us cheap 130 mg viagra extra dosage overnight delivery. In its original development erectile dysfunction 2 purchase viagra extra dosage 150mg with visa, the concept of hormesis pertained to the ability of substances to stimulate biological systems at low doses but to inhibit them at high doses erectile dysfunction following radical prostatectomy order viagra extra dosage 130mg otc. The application of the concept of hormesis to whole-animal toxicologic dose­response relationships may also be relevant but requires that the "response" on the ordinate be variant with dose erectile dysfunction doctors in kansas city buy discount viagra extra dosage 200mg on line. For example, chronic alcohol consumption is well recognized to increase the risk of esophageal cancer, liver cancer, and cirrhosis of the liver at relatively high doses, and this response is dose-related Threshold Another important aspect of the dose­response relationship at low doses is the concept of the threshold. It has long been recognized that acute toxicologic responses are associated with thresholds; that is, there is some dose below which the probability of an individual responding is zero. Obviously, the identification of a threshold depends on the particular response that is measured, the sensitivity of the measurement, and the number of subjects studied. For the individual dose­response relationship, thresholds for most toxic effects certainly exist, although interindividual variability in response and qualitative changes in response pattern with dose make it difficult to establish a true "no effects" threshold for any chemical. The biological basis of thresholds for acute responses is well established and frequently can be demonstrated on the basis of mechanistic information (Aldridge, 1986). The traditional approaches to establishing acceptable levels of exposure to chemicals are inherently different for threshold versus nonthreshold responses. The existence of thresholds for chronic responses is less well defined, especially in the area of chemical carcinogenesis. It is, of course, impossible to scientifically prove the absence of a threshold, as one can never prove a negative. Nevertheless, for the identification of "safe" levels of exposure to a substance, the absence or presence of a threshold is important for practical reasons (see Chap. Both types of tumors demonstrated increasing incidence with increasing dose, but the shapes of the two curves are dramatically different. For liver tumors, no clear threshold was evident, whereas for bladder tumors, an apparent threshold was evident. Of course, the ability to detect a low incidence of tumors depends on the number of animals used in the study. Thus, although a threshold (a dose below which no response occurs) appears evident for bladder tumors in. The existence or lack of existence of a threshold dose for carcinogens has many regulatory implications and is a point of considerable controversy and research in the field of quantitative risk assessment for chemical carcinogens (see Chap. Assumptions in Deriving the Dose­Response Relationship A number of assumptions must be considered before dose­response relationships can be used appropriately. To describe the relationship between a toxic material and an observed effect or response, one must know with reasonable certainty that the relationship is indeed a causal one. For some data, it is not always apparent that the response is a result of chemical exposure. For example, an epidemiologic study might result in the discovery of an "association" between a response. Frequently, the data are presented similarly to the presentation of "dose response" in pharmacology and toxicology. Use of the dose response in this context is suspect unless other convincing evidence supports a causal connection between the estimated dose and the measured endpoint (response). Unfortunately, in nearly all retrospective and case-control studies and even in many prospective studies, the dose, duration, frequency, and routes of exposure are seldom quantified, and other potential etiologic factors are frequently present. In its most strict usage, then, the dose­response relationship is based on the knowledge that the effect is a result of a known toxic agent or agents. A second assumption seems simple and obvious: the magnitude of the response is in fact related to the dose. Perhaps because of its apparent simplicity, this assumption is often a source of misunderstanding. There is a molecular target site (or sites) with which the chemical interacts to initiate the response. The production of a response and the degree of response are related to the concentration of the chemical at the target site. The third assumption in using the dose­response relationship is that there exists both a quantifiable method of measuring and a precise means of expressing the toxicity. For any given dose­response relationship, a great variety of criteria or endpoints of toxicity could be used. The ideal criterion would be one closely associated with the molecular events resulting from exposure to the toxicant. It follows from this that a given chemical may have a family of dose­response relationships, one for each toxic endpoint. Early in the assessment of toxicity, little mechanistic information is usually available; thus establishing a dose­response relationship based on the molecular mechanism of action is usually impossible. In the absence of a mechanistic, molecular ideal criterion of toxicity, one looks to a measure of toxicity that is unequivocal and clearly relevant to the toxic effect. The percent of animals with liver (blue line) or bladder (black line) tumors at 24 months (A) or 33 months (B) are shown. Most of the animals in the high-dose group (150 ppm) did not survive to 33 months; thus, those data are not shown in B. Saturation of biotransformation pathways, protein-binding sites or receptors, and depletion of intracellular cofactors represent some reasons why sharp inflections in the dose­response relationship may occur. For example, the widely used analgesic acetaminophen has a very low rate of liver toxicity at normal therapeutic doses. This effect is analogous to the rapid change in pH of a buffered solution that occurs when the buffer capacity is exceeded. Some toxic responses, most notably the development of cancer after the administration of genotoxic carcinogens, are often considered to be linear at low doses and thus do not exhibit a threshold. In this way, one would be measuring, in a readily accessible system and using a technique that is convenient and reasonably precise, a prominent effect of the chemical and one that is usually pertinent to the mechanism by which toxicity is produced. The selection of a toxic endpoint for measurement is not always so straightforward. Even the example cited above may be misleading, as an organophosphate may produce a decrease in blood cholinesterase, but this change may not be directly related to its toxicity. As additional data are gathered to suggest a mechanism of toxicity for any substance, other measures of toxicity may be selected. Although many endpoints are quantitative and precise, they are often indirect measures of toxicity. Use of these enzymes in serum is yet another example of an effects-related biomarker because the change in enzyme activity in the blood is directly related to damage to liver cells. Much of clinical diagnostic medicine relies on effects-related biomarkers, but to be useful the relationship between the biomarker and the disease must be carefully established. Patterns of isozymes and their alteration may provide insight into the organ or system that is the site of toxic effects. As discussed later in this chapter, the new tools of toxicogenomics provide an unprecedented opportunity to discover new "effects-related biomarkers" in toxicology. Many direct measures of effects are also not necessarily related to the mechanism by which a substance produces harm to an organism but have the advantage of permitting a causal relation to be drawn between the chemical and its action. For example, measurement of the alteration of the tone of smooth or skeletal muscle for substances acting on muscles represents a fundamental approach to toxicological assessment. Similarly, measures of heart rate, blood pressure, and electrical activity of heart muscle, nerve, and brain are examples of the use of physiologic functions as indices of toxicity. Measurement can also take the form of a still higher level of integration, such as the degree of motor activity or behavioral change. The measurements used as examples in the preceding discussion all assume prior information about the toxicant, such as its target organ or site of action or a fundamental effect. However, such information is usually available only after toxicological screening and testing based on other measures of toxicity. With a new substance, the customary starting point is a single dose acute toxicity test designed to provide preliminary identification of target organ toxicity. Studies specifically designed with lethality as an end-point are no longer recommended by United States or international agencies. Data from acute studies provides essential information for choosing doses for repeated dosing studies as well as choosing specific toxicological endpoints for further study. Key elements of the study design must be a careful, disciplined, detailed observation of the intact animal extending from the time of administration of the toxicant to any clinical signs of distress, which may include detailed behavioral observations or physiological measures. From properly conducted observations, immensely informative data can be gathered by a trained toxicologist. Second, an acute toxicity study ordinarily is supported by histological examination of major tissues and organs for abnormalities. From these observations, one can usually obtain more specific information about the events leading to the various Figure 2-9. The plot is of log dosage versus percentage of population responding in probit units. It is tempting to view the parallel dose­response curves as indicative of identity of mechanism-that is, to conclude that the lethality is a simple extension of the therapeutic effect. Whereas this conclusion may ultimately prove to be correct in any particular case, it is not warranted solely on the basis of the two parallel lines. The same admonition applies to any pair of parallel "effect" curves or any other pair of toxicity or lethality curves. The concept of the "therapeutic index," which was introduced by Paul Ehrlich in 1913, can be used to illustrate this relationship. Although the therapeutic index is directed toward a comparison of the therapeutically effective dose to the toxic dose of a chemical, it is equally applicable to considerations of comparative toxicity. Similarly, an index of comparative toxicity is obtained by the ratio of doses of two different materials to produce an identical response or the ratio of doses of the same material necessary to yield different toxic effects. Schematic representation of the difference in the dose­response curves for four chemicals (A­D), illustrating the difference between potency and efficacy (see text). However, the use of the median effective and median toxic doses is not without disadvantages, because median doses tell nothing about the slopes of the dose­response curves for therapeutic and toxic effects. A measure of the degree of accumulation of a chemical and/or its toxic effects can also be estimated from quantal toxicity data. Theoretically, if no cumulative effect occurs over the doses, the chronicity index will be 1. This index compares the estimated daily exposure, in milligrams per kilogram per day, that might occur under a given set of circumstances to some estimated value from the quantal dose­response relationship. Thus, for example, if an estimate of human exposure to a pesticide residue yielded a value of 0. This value indicates that the estimate of daily exposure under the described set of conditions is 1/1000 the estimated daily dose that would cause evident toxicity in 10% of exposed animals. One can then compare the potency and maximal efficacy of the two chemicals to produce a toxic effect. Chemical A is said to be more potent than chemical B because of their relative positions along the dosage axis. Potency thus refers to the range of doses over which a chemical produces increasing responses. Maximal efficacy reflects the limit of the dose­response relationship on the response axis to a certain chemical. Chemicals A and B have equal maximal efficacy, whereas the maximal efficacy of C is less than that of D. The living matter that is injured is termed the uneconomic form (or undesirable), and the matter protected is called the economic form (or desirable). They may be related to each other as parasite and host or may be two tissues in one organism. This biological diversity interferes with the ability of ecotoxicologists to predict the toxic effects of a chemical in one species (humans) from experiments performed in another species (laboratory animals). However, by taking advantage of the biological diversity, it is possible to develop chemicals that are lethal for an undesired species and harmless for other species. In agriculture, for example, there are fungi, insects, and even competitive plants that injure the crop, and thus selective pesticides are needed. Similarly, animal husbandry and human medicine require chemicals, such as antibiotics, that are selectively toxic to the undesirable form but do not produce damage to the desirable form. Drugs and other chemicals used for selective toxic purposes are selective for one of two reasons. Either (1) the chemical is equally toxic to both economic and uneconomic cells but is accumulated mainly by uneconomic cells or (2) it reacts fairly specifically with a cytological or a biochemical feature that is absent from or does not play an important role in the economic form (Albert, 1965, 1973). Selectivity resulting from differences in distribution usually is caused by differences in the absorption, biotransformation, or excretion of the toxicant. The selective toxicity of an insecticide spray may be partly due to a larger surface area per unit weight that causes the insect to absorb a proportionally larger dose than does the mammal being sprayed. The effectiveness of radioactive iodine in the treatment of hyperthyroidism (as well as its thyroid carcinogenicity) is due to the selective ability of the thyroid gland to accumulate iodine. A major reason why chemicals are toxic to one, but not to another, type of tissue is that there are differences in accumulation of the ultimate toxic compound in various tissues. This, in turn, may be due to differences in the ability of various tissues to transport or biotransform the chemical into the ultimate toxic product. Selective toxicity caused by differences in comparative cytology is exemplified by a comparison of plant and animal cells. Plants differ from animals in many ways-for example, absence of a nervous system, an efficient circulatory system, and muscles as well as the presence of a photosynthetic mechanism and cell walls. The fact that bacteria contain cell walls and humans do not has been utilized in developing selective toxic chemotherapeutic agents, such as penicillin and cephalosporins, that kill bacteria but are relatively nontoxic to mammalian cells. Selective toxicity can also be a result of a difference in biochemistry in the two types of cells. For example, bacteria do not absorb folic acid but synthesize it from p-aminobenzoic acid, glutamic acid, and pteridine, whereas mammals cannot synthesize folic acid but have to absorb it from the diet.

Syndromes

• Swollen spleen and liver
• Constipation (hard stools)
• Corneal transplant replaces a damaged or diseased cornea. The cornea is the clear tissue on the front of the eye that helps focus light on the retina. It is the part of the eye on which a contact lens rests.
• Enlarged (dilated) pupils
• Does the bleeding always occur on one or both sides?
• Dilantin
• Kidney disease

If we finalize this proposal erectile dysfunction doctors in brooklyn buy cheap viagra extra dosage 200mg line, this change would take effect on the effective date of the final rule with comment period erectile dysfunction what doctor to see proven 200 mg viagra extra dosage, which would occur during the 2022 recertification cycle erectile dysfunction what to do 120 mg viagra extra dosage sale. We are proposing to calculate the expected donation rate using 12 of the 24 months of data following the effective date of the final rule with comment period (using data from January 1 erectile dysfunction drugs thailand buy 130 mg viagra extra dosage overnight delivery, 2020 through December 31 erectile dysfunction due to drug use order viagra extra dosage 130 mg on line, 2020) hcpcs code for erectile dysfunction pump buy viagra extra dosage 150mg with mastercard. The CoPs for transplant centers set forth the requirements each transplant center must meet to be eligible for payment under the Medicare. If recommending another outcome measure, what is the empirical evidence for that recommended measure? If yes, identify the specific requirements and how they would harmonize or otherwise modify the requirements. We are especially interested in public comments about the validity and reliability of these possible measures. The first potential measure would be the actual deceased donors as a percentage of inpatient deaths among patients 75 years of age or younger with a cause of death consistent with organ donation. We believe that the consistency and quality of this measure could be a significant improvement over the current measures because it relies on independent data to measure true organ donation potential. This outcome measure also would account for: (1) Geographic differences in the manner of deaths across the United States (for example, trauma deaths); (2) geographic differences in the age distribution of deaths; and (3) geographic differences in in-hospital versus out-of-hospital deaths. This measure would reward efforts to maximize total organ procurement and efforts to improve placements of all procured organs. The second potential measure is the actual organs transplanted as a percentage of inpatient deaths among patients 75 years of age or younger with a cause of death consistent with organ donation. This measure also would reward efforts to maximize total organ procurement and efforts to improve placements of all procured organs. In addition to public comments on both of these potential outcome measures, we are interested in public comments on appropriate parameters for these measures. If commenters cannot recommend a specific percentage, how should we determine what the parameters for the outcome measures should be? We are requesting that commenters explain and include any evidence or data they have to support their comments. We noted that payment for the test is usually bundled with payment for the hospital service, even when the results of the test did not guide treatment during the hospital stay. When the 14-day rule applies, laboratory tests are not bundled into the hospital stay, but are instead paid separately under Medicare Part B (as explained in more detail below). For additional information on these potential outcome measures, we refer readers to the document, Changing Metrics of Organ Procurement Organization Performance in Order to Increase Organ Donation Rates in the United States, published in the American Journal for Transplantations. Clinical Laboratory Fee Schedule: Potential Revisions to the Laboratory Date of Service Policy A. However, a laboratory service may take place over a period of time-the date the laboratory test is ordered, the date the specimen is collected from the patient, the date the laboratory accesses the specimen, the date the laboratory performs the test, and the date results are produced may occur on different dates. In that case, the hospital would bill Medicare for the test and then would pay the laboratory that performed the test, if the laboratory provided the test under arrangement. Or: · Criterion (B): the test is cleared or approved by the Food and Drug Administration. Therefore, we agreed with the commenters that the laboratory performing the test should be permitted to bill Medicare directly for these tests, instead of relying on the hospital to bill Medicare on behalf of the laboratory under arrangements. According to stakeholders, the performing laboratory requires this information so that it can bill Medicare directly for the test instead of seeking payment from the hospital. According to these stakeholders, blood banks and blood centers that are not currently enrolled in the Medicare program would need to establish a billing mechanism so that they can bill Medicare directly when the requirements of § 414. In those circumstances, the hospital had to bill Medicare for the test, and the laboratory had to seek payment from the hospital. In contrast, if the results of the test are not intended to guide treatment during a hospital outpatient encounter, and if all other requirements in § 414. Under this approach, the test would be considered a hospital service unless the ordering physician determines that the test does not guide treatment during a hospital outpatient encounter. In this situation, the test would not be considered a hospital service and the performing laboratory would be required to bill for the test. As a result, the hospital that collected the specimen would bill for the laboratory test under arrangements and the laboratory would seek payment from the hospital for the test. We also acknowledged that hospitals may not currently have the technical expertise or certification requirements necessary to perform molecular pathology testing and therefore must rely on independent laboratories to perform the test. We also are interested in receiving public comments regarding the administrative aspects of requiring the ordering physician to determine when the test results are not intended to guide the treatment during a hospital outpatient encounter, as well as the process for the ordering physician to document this decision and provide notification to the hospital that collected the specimen for billing purposes. These exceptions would continue to include the requirement that the results of the test do not guide treatment provided during the hospital stay, meaning the hospital stay in which the specimen was collected. Although we recognize that the considerations about how a hospital service is determined under § 414. We note that we would consider finalizing this approach as a result of the public comments received. Representatives of blood banks and centers contend that while these entities may perform the same molecular pathology tests that are performed and billed by other laboratories that are not blood banks and centers, the blood banks and centers perform these tests for different reasons. Specifically, they assert that the blood banks and centers perform molecular pathology testing primarily to identify the most compatible blood product for a patient, whereas other laboratories typically provide molecular pathology testing for diagnostic purposes. According to these stakeholders, the patient has already been diagnosed with a specific disease or condition before the blood sample is provided to the blood bank or center, who are then tasked with providing compatible blood products and assessing risks of incompatibility for hospitals. In other words, blood banks and centers perform molecular pathology testing for patients to enable hospitals to prevent adverse conditions associated with blood transfusions, rather than perform molecular pathology testing for diagnostic purposes. This would include circumstances when a laboratory that is a blood bank or blood center performs the test. We are concerned that our current policy may unbundle molecular testing performed by a blood bank or center for a hospital patient. As such, we believe that molecular pathology testing, when performed by blood banks or centers, is inherently tied to a hospital service because hospitals receive payment for and/or use the blood and/or blood products provided by blood banks and blood centers to treat patients in the hospital setting. Accordingly, we believe that such testing is so connected to the treatment furnished to the patient in the hospital that it must be considered a hospital service and that hospitals should be permitted to bill and receive payment for such testing performed on these blood and/or bloodrelated products. As a result, the hospital would bill for the laboratory test under arrangements and the blood bank or center performing the test would seek payment from the hospital. In addition, for purposes of excluding blood banks and centers from the provisions of § 414. We believe this potential definition of a blood bank and center describes the primary responsibility of all blood banks and centers, which distinguishes these entities from other laboratory types. In developing a definition of blood banks and centers we are distinguishing blood banks and blood centers from non-blood 39603 bank and blood center laboratories that perform the same molecular pathology test codes but for different reasons, that is, for diagnostic purposes rather than for blood compatibility testing. We also are requesting specific comments as to how a blood bank and blood center may be defined in the context of this provision, and particularly how to distinguish blood banks and centers from other laboratories. As an initial effort to focus our analysis, we chose to target services that represent procedures that are likely to be cosmetic surgical procedures and/or are directly related to cosmetic surgical procedures that are not covered by Medicare, but may be combined with or masquerading as therapeutic services. Therefore, these aboveaverage increases in volume suggest an increase in unnecessary utilization. We believe prior authorization for these services will be an effective method for controlling increases in the volume of these services because we expect that it will reduce the instances in which Medicare pays for these services when they are merely cosmetic and not medically necessary. This includes improvements in interoperability, the secure electronic transmission of clinical data, and the potential incorporation of artificial intelligence into the claims review process. As stated earlier, we are proposing to establish a new subpart I under part 419 (containing §§ 419. Basis, Scope, and Definitions for Proposed New Subpart I Under Part 419 We are proposing to specify the basis and scope of the proposed subpart under proposed new § 419. We are proposing to define ``prior authorization' to mean a and the average annual rate-of-increase in Medicare allowed amounts. Our analysis also showed an average annual rate-of-increase in the Medicare allowed amount (the amount that Medicare would pay for services regardless of external variables, such as beneficiary plan differences, deductibles, and appeals) of 8. Many of these services fall within the following five general categories of services: (1) Blepharoplasty; (2) botulinum toxin injections; (3) panniculectomy; (4) rhinoplasty; and (5) vein ablation. Prior Authorization as a Method for Controlling Unnecessary Increases in the Volume of Covered Outpatient Services (Proposed New § 419. This would include the denial of any claims associated with the denial of a service listed in proposed § 419. Moreover, we are proposing that even when a provisional affirmation has been received, a claim for services may be denied based on either technical requirements that can only be evaluated after the claim has been submitted for formal processing or information not available at the time the prior authorization request is received (proposed new § 419. As noted earlier, we are proposing that, in submitting a prior authorization request, the provider must include all relevant documentation necessary to show that the service meets applicable Medicare coverage, coding, and payment rules and that the request be submitted before the service is provided to the beneficiary and before the claim is submitted (proposed new § 419. We are proposing that, if the provider receives a non-affirmation decision, we would allow the provider to resubmit a prior authorization request with any applicable additional relevant documentation. This would include the resubmission of requests for expedited reviews (proposed new § 419. However, the provider will still have the opportunity to resubmit a prior authorization request under proposed new § 419. These associated services include, but are not limited to , services such as anesthesiology services, physician services, and/or facility services. The associated claims would be denied whether a non-affirmation was received for a service listed in proposed new § 419. A contractor is not required to request medical documentation from the provider who billed the associated claims before making such a denial. We are requesting public comments on whether the requirement in proposed new § 419. Proposed List of Outpatient Department Services That Would Require Prior Authorization (Proposed New § 419. Proposed List of Outpatient Department Services Requiring Prior Authorization As mentioned earlier, we have identified a list of specific services (Table 38) that, based on review and analysis of claims data for the 11-year period from 2007 through 2017, show higher than expected, and therefore, we believe, unnecessary, increases in the volume of service utilization. These services fall within the following five categories: blepharoplasty; botulinum toxin injections; panniculectomy; rhinoplasty; and vein ablation. In making the decision to propose to include the specific services in the proposed list of hospital outpatient department services requiring prior authorization as shown in Table 38, we first considered that these services are most often considered cosmetic and, therefore, are only covered by Medicare in very rare circumstances. We then viewed the current volume of utilization of these services and determined that the utilization far exceeds what would be expected in light of the average rateof-increase in the number of Medicare beneficiaries. We note that we are unaware of other factors that might contribute to increases in volume of services that indicate that the services are increasingly medically necessary, such as clinical advancements or expanded coverage criteria that would have led to the increases. Based on analysis and comparisons of claims data, these increases in service utilization volume, financial expense, and the number of Medicare patients far exceed the typical baseline rates or trends we identified. Based on analysis and comparisons of claims data, these increases in service utilization volume, financial expense to the Medicare program, and the number of Medicare patients also far exceed the typical baseline rates or trends we identified (that is, the 9. Even though this category of services includes some procedures that had annual increases in service utilization volume far exceeding what we would expect based on the typical rate, this was not true for all services within the category. The five categories of services would be: Blepharoplasty; botulinum toxin injections; panniculectomy; rhinoplasty; and vein ablation. We would exempt providers that achieve a prior authorization provisional affirmation threshold of at least 90 percent during a semiannual assessment. We anticipate that an exemption will take approximately 90 calendar days to effectuate. We believe that, by achieving this percentage, the provider would be demonstrating an understanding of the requirements for submitting accurate claims. We do not believe it is necessary for a provider to achieve 100 percent compliance to qualify for an exemption because innocent and sporadic errors could occur that are not deliberate or systematic attempts to submit claims that are not payable. If the rate of nonpayable claims submitted becomes higher than 10 percent during a biannual assessment, we will consider withdrawing exemption. Again, we anticipate that withdrawing the exemption may take approximately 90 calendar days to effectuate. While we believe this is unlikely to occur, we nonetheless believe it is necessary for us to retain this flexibility in the event of certain circumstances, such as where the cost of the prior authorization program exceeds the savings it generates. This rate increased significantly more than the expected rate and was as much as 34. However, some procedures had annual increases in service utilization volume that far exceeded these expected rates. As an example, the number of unique claims for the procedure of repairing of the upper eyelid muscle to correct drooping or paralysis increased as high 39607 as 48. Table 38 lists the specific procedures within the five categories of services that we are proposing for the proposed list of hospital outpatient department services requiring prior authorization. For this cause, the Department is seeking public comments, including comments from hospitals and revenue cycle management experts, cost report experts, accounting firms, or others who understand hospital cash flows, on innovative and streamlined methods for establishing hospital payment to the extent permitted by law. The cost report contains provider information such as facility characteristics, utilization data, cost and charges by cost center (in total and for Medicare), Medicare settlement data, and financial statement data. We are seeking public comments on the continued value of the chargemaster charges in setting hospital payment and to other stakeholders, as well as the costs associated with maintaining the chargemaster for purposes of Medicare cost reporting and payment. Further, we are seeking public comments on whether it would be possible to modernize or streamline the Medicare cost reporting process, for example, by replacing it with other processes or if it could be modified in content, methodology, or approach. We also are seeking public comments on the decision process, and why the chargemaster might be updated more frequently than on an annual basis and how this more frequent updating could affect costs for patients. Additionally, we are seeking public comment on whether this proposal could create unintended or inadvertent consequences. As part of our ongoing efforts to reduce regulatory burdens, we have continued to examine areas in which the rules for co-located entities are no longer necessary. Below we discuss only the changes in burden that would result from the proposed policies in this proposed rule with comment period, if finalized. We note that since then, more recent wage data have become available, and we are updating the wage rate used in these calculations.

Van den Berg M erectile dysfunction from diabetes treatment for viagra extra dosage 120 mg generic, Heeremans C impotence liver disease buy discount viagra extra dosage 130mg on line, Veerhoven E erectile dysfunction and injections buy viagra extra dosage 200 mg without a prescription, Olie K: Transfer of polychlorinated dibenzo- p-dioxins and dibenzofurans to fetal and neonatal rats erectile dysfunction after stopping zoloft buy 150 mg viagra extra dosage overnight delivery. Yuasa H erectile dysfunction pumpkin seeds buy viagra extra dosage 150mg with mastercard, Matsuhisa E chewing tobacco causes erectile dysfunction order viagra extra dosage 130mg on line, Watanabe J: Intestinal brush border transport mechanism of 5-fluorocuracil in rats. Glycopyrrolate is a quaternary ammonium salt, hence, it is positively charged at physiological pH. The mean elimination half-life increases from 19 minutes in patients with normal kidney function to 47 minutes in patients with severe kidney impairment, indicating that renal disease impairs the elimination of glycopyrrolate. Although it is excreted in the urine largely as unchanged drug, glycopyrrolate reinforces a number of principles about xenobiotic biotransformation, the most important of which is: xenobiotic biotransformation is the process-actually a series of enzyme-catalyzed processes-that alters the physiochemical 161 properties of foreign chemicals (xenobiotics) from those that favor absorption across biological membranes (namely, lipophilicity) to those favoring elimination in urine or bile (namely, hydrophilicity). Without xenobiotic biotransformation, the numerous foreign chemicals to which we are exposed (which includes both man-made and natural chemicals such as drugs, industrial chemicals, pesticides, pollutants, pyrolysis products in cooked food, alkaloids, secondary plant metabolites, and toxins produced by molds, plants, etc. Furthermore, absent xenobiotic biotransformation, many of the drugs in use today would have an unacceptably long duration of action. In contrast, drugs that are not lipophilic, like glycopyrrolate, are not absorbed from the gastrointestinal tract (hence they are not orally active), and if they are administered parenterally they are not biotransformed (because they are already hydrophilic), and they are rapidly eliminated from the body. The enzymes that catalyze xenobiotic biotransformation are often called drug-metabolizing enzymes. This acronym is used widely in the pharmaceutical industry to Copyright © 2008 by the McGraw-Hill Companies, Inc. This chapter describes some fundamental principles of xenobiotic biotransformation, and describes the major enzyme systems involved in the biotransformation (or metabolism) of drugs and other xenobiotics. The examples given are biased toward drugs and human enzyme systems for two reasons. First, many of the fundamental principles of xenobiotic biotransformation stem from such studies. This is especially true of drugs with a narrow therapeutic index (where the toxic dose is not much greater than the therapeutic dose), which have revealed a large number of genetic and environmental factors that affect xenobiotic biotransformation and, hence, drug toxicity. Second, adverse drug reactions are one of the leading causes of death in the United States. Nevertheless, the following points, which might be considered principles or rules, apply in the majority of cases: Point 1 Xenobiotic biotransformation or drug metabolism is the process of converting lipophilic (fat soluble) chemicals, which are readily absorbed from the gastrointestinal tract and other sites, into hydrophilic (water soluble) chemicals, which are readily excreted in urine or bile. For example, acetylation and methylation are biotransformation reactions that can actually decrease the water solubility of certain xenobiotics. Point 2 the biotransformation of xenobiotics is catalyzed by various enzyme systems that can be divided into four categories based on the reaction they catalyze: 1. The conjugation reactions include glucuronidation, sulfonation (often called sulfation), acetylation, methylation, conjugation with glutathione (mercapturic acid synthesis) and conjugation with amino acids (such as glycine, taurine, and glutamic acid). Examples of the major chemical groups that undergo biotransformation together with the enzymes that commonly mediate their biotransformation are given in Table 6-2 (Williams et al. Xenobiotic biotransformation is generally catalyzed by enzymes, but there are exceptions. For example, hydrolysis of certain carboxylic and phosphoric acid esters, reduction of sulfoxides to sulfides. Point 3 In general, individual xenobiotic-biotransforming enzymes are located in a single organelle. However, in such cases, the enzyme name generally refers to two or more enzymes, each with its own distinct subcellular location. For example, the epoxide hydrolase located in microsomes is a different enzyme from the epoxide hydrolase located in cytosol. From a practical perspective, it is noteworthy that during the homogenization of tissue and the preparation of subcellular fractions, a certain degree of cross-contamination of organelles occurs. For example, microsomes contain detectable levels of monoamine oxidase due to their contamination with the outer mitochondrial membrane. Point 4 In general, xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities. The broad and sometimes overlapping substrate specificities of xenobioticbiotransforming enzymes preclude the possibility of naming the individual enzymes after the reactions they catalyze (which is how most other enzymes are named). Many of the enzymes involved in xenobiotic biotransformation are named according to nomenclature systems based on the primary amino acid sequence of the individual enzymes. Some enzymes are given the same name across all mammalian species, whereas others are named in a species-specific manner. In general, a variant form of a xenobiotic-biotransforming enzyme (known as an allelic variant or an allelozyme) has diminished enzymatic activity compared with that of the wild-type enzyme, although this is not always the case (see section "Alcohol Dehydrogenase"). The impact of amino acid substitution(s) on the catalytic activity of a xenobioticbiotransforming enzyme may be substrate dependent, such that an allelic variant may interact normally with some substrates (and inhibitors) but interact atypically with others. The classification of xenobioticbiotransforming enzymes into Phase 1 and Phase 2 (and the extension of this system to classify xenobiotic transporters as Phase 3) has been criticized lately by Josephy et al. First, although the conjugation of many xenobiotics is preceded by hydrolysis, reduction, or oxidation (such that xenobiotics can be said to undergo Phase 1 before Phase 2 metabolism), there are several cases where a xenobiotic undergoes oxidation after it has been conjugated (such that Phase 2 precedes Phase 1 metabolism). For example, gemfibrozil is conjugated with glucuronic acid before it undergoes oxidation by cytochrome P450 (Ogilvie et al. For example, the majority of acetaminophen (Tylenol) is conjugated directly with glucuronic acid and, to a lesser extent, sulfonic acid. Third, the original idea that Phase 2 metabolism results in only detoxication is incorrect. Indeed, all xenobiotic-metabolizing enzymes are capable of increasing the toxicity of one or more xenobiotics, including the conjugating enzymes that R. In this chapter, the terms Phase 1 and Phase 2 metabolism will not be used; instead the pathways of xenobiotic biotransformation will be divided into four categories: hydrolysis, reduction, oxidation, and conjugation. Point 6 Not all biotransformation reactions are catalyzed by the mammalian enzymes listed in Table 6-1. Some biotransformation reactions are catalyzed by enzymes in the gut microflora (largely anaerobic bacteria in the colon), whereas the biotransformation of still other xenobiotics is catalyzed by enzymes that participate in intermediary (endobiotic) metabolism. Examples of xenobiotic biotransformation by different enzyme systems: a xenobiotic-biotransforming enzyme (cytochrome P450), an endobiotic-metabolizing enzyme, and gut microflora. Cinnamic acid is also converted to benzoic acid but, in this case, the reaction is catalyzed by the mitochondrial enzymes involved in the -oxidation of fatty acids. Quinic acid is also converted to benzoic acid, but this reductive, multistep reaction is catalyzed by gut microflora. Incidentally, the conversion of benzoic acid to hippuric acid is of historical interest because it is generally recognized as the first xenobiotic biotransformation reaction to be discovered (in dogs by Woehler in 1828, and in humans by Ure in 1841). Some drugs are intentionally designed to be biotransformed by endobiotic-metabolizing enzymes. The luminal surface of the small intestine contains high levels of alkaline phosphatase, which hydrolyzes prodrugs like fosamprenavir and thereby releases the active drug at the surface of the enterocyte, where it is readily absorbed. Generally speaking, kinase and alkaline phosphatase are not usually considered to be xenobiotic-biotransforming enzymes. Point 7 Just as some xenobiotics are biotransformed by the so-called endobiotic-metabolizing enzymes (Point 6), certain endobiotics are biotransformed by the so-called xenobiotic-metabolizing enzymes. From the few examples in Points 6 and 7, it is apparent that, on a case-by-case basis, there is no clear-cut distinction between endobiotic- and xenobiotic-biotransforming enzymes. The human genome project has helped to establish that what were once thought to be two distinct enzymes, one involved in the metabolism of endobiotics and one involved in the metabolism of xenobiotics, are in fact one and the same enzyme. For example, the microsomal enzyme known as 11-hydroxysteroid dehydrogenase is identical to the xenobiotic-metabolizing enzyme known as microsomal carbonyl reductase. These examples illustrate how xenosensors are not just involved in xenobiotic disposition but also play a role in endobiotic homeostasis. The induced enzymes (and transporters) usually accelerate the elimination of the xenobiotic that triggered the induction process, in which case the xenobiotic is said to be an auto-inducer (one that induces its own metabolism). However, xenobiotics often induce enzymes that are not capable of metabolizing them, in which case the induction is said to be gratuitous. Point 9 the ability of certain xenobiotic-biotransforming enzymes to metabolize hormones and other endobiotics (Point 7) and the ability of certain xenobiotics to induce xenobioticbiotransforming enzymes (Point 8) have implications for understanding an important mechanism by which certain xenobiotics can alter homeostasis or cause toxicity. Persistent exposure to enzyme inducers can also cause liver tumors, although the mechanism is not fully understood. Activation of certain xenosensors is critical to liver tumor development, although upregulation of xenobioticbiotransforming enzymes appears to be less important than other xenosensor-dependent events, such as the down-regulation of gap junctional proteins, which diminishes cell­cell communication. Phenobarbital, Wy-14,643, methapyrilene, and Ponceau S are representatives of four classes of nongenotoxic rodent tumorigens (epigenetic tumor promoters) that cause hepatocellular hyperplasia and hypertrophy in association with proliferation of the endoplasmic reticulum, peroxisomes, mitochondria, and lysosomes, respectively (Grasso et al. Prolonged activation of these receptors in rodents results in the development of liver and/or thyroid tumors. At one time, the management of neonatal jaundice included treatment with phenobarbital to induce bilirubin conjugation, but this practice has been discontinued. However, the Chinese herbal Yin Zhi Wuang (active ingredient scoparone) is still used to treat neonatal jaundice. Point 10 Xenobiotic biotransformation can alter the biological properties of a xenobiotic. It can make the xenobiotic less toxic (detoxication), but in some cases it can make it more toxic (activation). The oxidation of ethanol (alcohol) to acetaldehyde is an example of xenobiotic activation, and the subsequent oxidation of acetaldehyde to acetic acid is an example of detoxication. The biotransformation of drugs can result in (1) a loss of pharmacological activity. Point 11 In many cases, the toxicity of a xenobiotic is due to the parent compound (the compound that was absorbed), in which case xenobiotic biotransformation serves as a detoxication mechanism. This is illustrated by the clinical observation that the incidence of adverse drug events is often higher in individuals with a poor metabolizer phenotype (discussed later in Point 23). Certain anticancer drugs require activation by xenobioticmetabolizing enzymes in order to exert their antineoplastic effects. Point 12 the toxicity and potential carcinogenicity of electrophilic metabolites produced by cytochrome P450 and other xenobiotic-biotransforming enzymes is reduced and often altogether eliminated by their conjugation with glutathione, which is often described as a noncritical cellular nucleophile. Conjugation with glutathione can occur both enzymatically (by glutathione Stransferase) and nonenzymatically. Point 14 the balance between activation and detoxication by xenobiotic-biotransforming enzymes is often a key determinant of chemical toxicity, and is often the basis for organ or species differences in toxicity. For example, aflatoxin is converted by liver microsomal cytochrome P450 to a reactive epoxide that is thought to be responsible for the hepatotoxic and hepatocarcinogenic effect of this mycotoxin. The fact that this reaction occurs in the liver explains why aflatoxin causes liver toxicity and liver tumors. On this basis, mice would be expected to be more sensitive than rats to the hepatotoxic effects of aflatoxin because mice catalyze the epoxidation of aflatoxin faster than rats. However, through glutathione conjugation, mice also detoxify aflatoxin epoxide faster than rats. Consequently, despite their slower rate of activation, rats are more susceptible than mice to the toxic effects of aflatoxin. This species difference is attributable to differences in the metabolites formed by cytochrome P450. Rats convert coumarin to a reactive epoxide that rearranges to a reactive aldehyde, whereas humans convert coumarin to the relatively nontoxic metabolite 7-hydroxycoumarin (umbelliferone). The enzymes involved in xenobiotic activation and detoxication play important roles in determining the susceptibility of mammals to the hepatotoxic effects of acetaminophen, which is the leading cause of acute liver failure in humans (Kaplowitz, 2005). The important point here is that the factors that determine whether a xenobiotic will or will not cause cellular toxicity go far beyond the enzymes involved in xenobiotic activation and detoxication, and these additional factors can also play a role in determining organ and species differences in xenobiotic toxicity. Point 15 Exposure to xenobiotics (especially drugs) is largely through oral ingestion, and the small intestine and liver are highly developed to limit systemic exposure to orally ingested xenobiotics, a process known as first-pass elimination (or presystemic elimination). The liver expresses a number of uptake transporters that actively remove xenobiotics from the blood. They also express a number of efflux transporters that actively discharge xenobiotics or their metabolites (especially conjugates) into the bile canaliculus for biliary excretion, or that actively discharge xenobiotic metabolites (especially conjugates) across the sinusoidal membrane back into the blood for urinary excretion. The liver expresses the largest number and, with few exceptions, the highest concentrations of xenobiotic-biotransforming enzymes. Although the liver contains higher concentrations of most xenobiotic-biotransforming enzymes, and because the number of hepatocytes in the liver exceeds the number of enterocytes in the small intestine, it might be assumed that, compared with the liver, the small intestine would make only a small contribution to first-pass metabolism, but this is not the case. The small intestine and liver are exposed to high concentrations of xenobiotics, and they possess high levels of the enzymes that potentially convert xenobiotics to reactive or toxic metabolites. It is perhaps not surprising, therefore, that both tissues possess protective mechanisms to minimize the risk of xenobiotic toxicity and carcinogenicity. As already mentioned, both tissues have enzymes and transporters that facilitate the elimination of xenobiotics and their metabolites. In both tissues, several of the xenobioticbiotransforming enzymes and transporters are inducible, enabling the liver and the small intestine to respond to high levels of xenobiotics by enhancing the rate of xenobiotic biotransformation and elimination. In the small intestine, the enterocytes at the villus tips undergo extensive turnover, such that the mature cells that are exposed to high levels of xenobiotics and/or reactive metabolites are quickly lost (exfoliated) and replaced in a matter of days. In liver, high levels of glutathione (5­10 mM), a large proportion of diploid (binucleated) cells, and a high regenerative capacity all protect the liver from xenobiotic toxicity or help the liver to repair chemicalmediated toxicity. In addition, severely damaged hepatocytes can undergo apoptosis (cell-programmed death) to eliminate precancerous cells. Point 16 Some of the same mechanisms that protect the small intestine and liver from xenobiotic toxicity also protect certain organs such as the brain and reproductive organs. Germ cells in the testis are protected in part by a blood­testis barrier, by high levels of glutathione (and glutathione transferase and glutathione peroxidase), and by high cell turnover (as in the case of enterocytes). Efflux transporters and glutathione transferases are often over-expressed in tumor cells as a result of chromosomal rearrangements that place the genes encoding these proteins under the control of a strong promoter. Point 17 In view of the important role of cytochrome P450 in the metabolic activation of proximate carcinogens to ultimate carcinogens, it may seem paradoxical to list cytochrome P450 induction among the defense mechanisms that protect organisms from the carcinogenic effects of xenobiotics. Activation by cytochrome P450 is definitely required for certain xenobiotics to exert their carcinogenic effects, and induction of cytochrome P450 is associated with an increase in the toxicity of certain xenobiotics. However, contrary to expectation, treatment of rodents with a cytochrome P450 inducer prior to treatment with a known proximate carcinogen (such as aflatoxin, various nitrosamines, or polycyclic aromatic hydrocarbons) is generally associated with a decrease, not an increase, in tumor incidence (Parkinson and Hurwitz, 1991). Nevertheless, enzyme induction appears, for the most part, to provide protection against chemical carcinogenesis. Point 18 Although the small intestine and liver contain the highest concentrations, xenobiotic-biotransforming enzymes are nevertheless widely distributed throughout the body.

However erectile dysfunction on molly generic viagra extra dosage 150 mg fast delivery, some soft tissue injuries best erectile dysfunction doctors nyc 120mg viagra extra dosage fast delivery, such as those resulting from nonpenetrating or penetrating forces erectile dysfunction causes in young men buy 200 mg viagra extra dosage amex, may be severe or life threatening and require immediate medical attention erectile dysfunction caused by vicodin buy viagra extra dosage 150mg low cost. Examples of minor soft tissue injuries include scrapes erectile dysfunction studies buy generic viagra extra dosage 130mg, bruises and mild sunburns boyfriend erectile dysfunction young 120 mg viagra extra dosage visa. Examples of serious soft tissue injuries include large cuts that require stitches and partial-thickness burns. Life-threatening soft tissue injuries include stab wounds to the abdomen, lacerations that cause severe bleeding and full-thickness burns. This chapter discusses the signs and symptoms of soft tissue injuries, including closed wounds, open wounds and burns, as well as signs and symptoms of infection. You will learn the differences between major wounds and minor wounds and between different types of burns. In addition, you will learn when to call 9-1-1 or the designated emergency number and how to give care. The Soft Tissues the soft tissues include the layers of skin, fat and muscle that protect the underlying body structures. As you learned in Chapter 4, the two primary layers of the skin are the outer layer, called the epidermis, that provides a barrier to bacteria and other organisms that can cause infection, and a deeper layer, called the dermis, that contains the nerves, sweat glands, oil glands and blood vessels. Because the skin is well supplied with blood vessels and nerves, most soft tissue injuries are likely to bleed and be painful depending on the severity of the injury. The subcutaneous layer (also called the hypodermis), located beneath the epidermis and dermis, contains adipose (fat), blood vessels and connective tissues. The adipose layer insulates the body to help maintain body temperature, mechanical cushion and, most importantly, a source of energy. The amount of adipose varies among the different parts of the body and from person to person. Although the muscles are considered soft tissues, muscle injuries are discussed more thoroughly in Chapter 11. The trauma of an injury may cause a blood vessel to tear, causing bleeding, but the blood at the wound site usually clots quickly and stops flowing. Sometimes, however, the damaged blood vessel is too large or the pressure in the blood vessel is too great for the blood to clot. Closed Wounds the simplest closed wound is a bruise, also called a contusion (Figure 10-1). Bruises result when the body is subjected to a blunt force, such as when you bump your leg on a table or chair. This bump or blow results in damage to soft tissue layers and vessels beneath the skin, causing internal bleeding. When blood and other fluids seep into the surrounding tissues, the area discolors and swells. The amount of discoloration and swelling varies depending on the severity of the injury. Over time, more blood and other fluids leak into the area, causing the area to turn dark red or purple. A significant violent force can cause injuries involving larger blood vessels, deeper layers of muscle tissue and internal organs. These injuries can result in severe bleeding beneath the skin that may become life threatening. As you learned in Chapter 8, signs and symptoms of severe internal bleeding include: Signs and symptoms of shock: { Skin that feels cool or moist and looks pale or bluish An altered level of consciousness A rapid, weak heartbeat Excessive thirst Tender, swollen or rigid areas of the body, such as the abdomen. Applying cold, however, can be effective early on in helping control both pain and swelling (Figure 10-2). When applying cold: Make a cold pack by filling a sealable plastic bag with a mixture of ice and water, and then apply it to the injured area for about 20 minutes. If an ice-and-water mixture is not available, use a bag of frozen vegetables or a chemical cold pack as an alternative. If the person is not able to tolerate a 20-minute application, limit application to 10 minutes. Elevating the injured part may help to reduce swelling; however, do not elevate the injured part if doing so causes more pain or you suspect a dislocation or fracture (see Chapter 11). Call 9-1-1 or the designated emergency number immediately if: A person complains of severe pain or cannot move a body part without pain. You think the force that caused the injury was great enough to cause serious damage. The person shows signs and symptoms of shock or becomes confused, drowsy or unresponsive. With all closed wounds, help the person to rest in the most comfortable position possible. If you suspect the person may be in shock, have them lie flat on their back and care for shock as described in Chapter 9. Be sure that a person with an injured lower extremity does not bear weight on it until advised to do so by a medical professional. Open Wounds In an open wound, the break in the skin can be as minor as a scrape of the surface layers or as severe as a deep penetration. The six main types of open wounds are abrasions, lacerations, avulsions, amputations, punctures/penetrations and crush injuries. It is characterized by skin that has been rubbed or scraped away, such as often occurs when a child falls and scrapes their hands or knees on a rough surface (road) (Figure 10-3). It is usually painful because scraping of the outer skin layers exposes sensitive nerve endings. Bleeding is not severe and is easily controlled, since only the small capillaries are damaged. Dirt and germs frequently have been rubbed into this type of wound, which is why it is important to clean and irrigate an abrasion thoroughly as described in the section, Specific Care for Minor Open Wounds. Responding to Emergencies 163 Soft Tissue Injuries Lacerations A laceration is a cut, which may have either jagged or smooth edges (Figure 10-4). Lacerations are commonly caused by sharp-edged objects, such as knives, scissors or broken glass. Deep lacerations can also affect the layers of adipose and muscle, as well as damaging both nerves and blood vessels. Lacerations usually bleed freely and, depending on the structures involved, can bleed heavily. Lacerations are not always painful because damaged nerves cannot transmit pain signals to the brain. Avulsions An avulsion is a serious injury in which a portion of the skin and sometimes other soft tissue is partially or completely torn away (Figure 10-5). Bleeding is usually significant because avulsions often involve deeper soft tissue layers. Responding to Emergencies 164 Soft Tissue Injuries Amputations Sometimes a body part, such as a finger, may be severed (Figure 10-6). Although damage to the tissue is severe when a body part is severed, bleeding may not be as bad as you might expect. The blood vessels usually constrict and retract (pull in) at the point of injury, slowing bleeding and making it relatively easy to control with direct pressure. Punctures/Penetrations A puncture/penetration wound results when the skin is pierced with a pointed object, such as a nail, a piece of glass, a splinter or a knife (Figure 10-7). Because the skin usually closes around the penetrating object, external bleeding is generally not severe. However, internal bleeding can be severe if the penetrating object damages major blood vessels or internal organs. An object that remains in the open wound is called an embedded object (Figure 10-8). An object may also pass completely through a body part, creating two open wounds-one at the entry point and one at the exit point. Although puncture wounds generally do not bleed profusely, they are more likely to become infected. Of particular danger is the microorganism that causes tetanus, a severe infection. Responding to Emergencies 165 Soft Tissue Injuries Crush Injuries A crush injury is the result of a body part, usually an extremity, being subjected to a high degree of pressure, in most cases after being compressed between two heavy objects (Figure 10-9). This type of injury may result in serious damage to underlying tissues and cause bleeding, bruising, fracture, laceration and compartment syndrome, which is swelling and an increase in pressure within a limited space that presses on and compromises blood vessels, nerves and tendons that run through that space. Crush syndrome is also common in people who are trapped in collapsed structures due to , for example, an earthquake or act of terrorism. General Care for Open Wounds General care for open wounds includes controlling bleeding and preventing infection. Using Dressings and Bandages All open wounds need some type of covering to help control bleeding and prevent infection. These coverings are commonly referred to as dressings and bandages, and there are many types. Dressings are pads placed directly on the wound to absorb blood and other fluids and to prevent infection. Standard dressings include varying sizes of cotton gauze, commonly ranging from 2 to 4 inches square. Much larger dressings are used to cover very large wounds and multiple wounds in one body area. Some dressings have nonstick surfaces to prevent the dressing from sticking to the wound (Figure 10-10). Different types of bandages are used to hold dressings in place, apply pressure to a wound, protect the wound from infection and provide support to an injured area. An occlusive dressing is a dressing that closes a wound or damaged area of the body and prevents it from being exposed to the air or water. By preventing exposure to the air, occlusive dressings help to further prevent infection. Occlusive dressings help keep in medications that are applied to the affected area. An example of an improvised occlusive dressing is plastic wrap secured with medical tape. This type of dressing is used for certain abdominal injuries that will be discussed in Chapter 14. Any bandage applied snugly to create pressure on a wound or an injury is called a pressure bandage. A common type of bandage is a commercially made adhesive compress or adhesive bandage (Figure 10-12). Available in assorted sizes, adhesive bandages consist of a small pad of nonstick gauze on a strip of adhesive tape that is applied directly to minor wounds. A bandage compress is a thick gauze dressing attached to a bandage that is tied in place. Bandage compresses are specially designed to help control severe bleeding and usually come in sterile packages. Roller bandages are available in assorted widths from Ѕ to 12 inches and lengths from 5 to 10 yards. A roller bandage may also be used to hold a dressing in place, secure a splint or control external bleeding (Figure 10-13). Responding to Emergencies 167 Soft Tissue Injuries Follow these general guidelines when applying a roller bandage: Check for feeling, warmth and color of the area distal to (below) the injury site, especially fingers and toes, before and after applying the bandage. Wrap the bandage around the body part until the dressing is completely covered and the bandage extends several inches beyond the dressing. By keeping these parts uncovered, you will be able to see if the bandage is too tight. If fingers or toes become cold or begin to turn pale, blue or ashen, the bandage is too tight and should be loosened slightly. If blood soaks through the bandage, apply more manual direct pressure over the wound and an additional dressing and another bandage as needed. Disturbing the dressing may disrupt the formation of a clot and restart the bleeding. To control severe, life-threatening bleeding, consider alternative techniques such as tourniquets and hemostatic dressings. Elastic roller bandages, sometimes called elastic wraps, are designed to keep continuous pressure on a body part (Figure 10-14). As with roller bandages, the first step in using an elastic bandage is to select the correct size of bandage: a narrow (2- or 3-inch) bandage is used to wrap a hand or wrist; a medium-width (3- to 4-inch) bandage is used for an arm or ankle, and a wide (6-inch) bandage is used to wrap an upper leg or shoulder. When properly applied, an elastic bandage can effectively control swelling or support an injured limb, as in the care for a venomous snakebite (see Chapter 17). An improperly applied elastic bandage can restrict blood flow, which is not only painful but can also cause tissue damage if not corrected. Elastic roller bandages can be applied to control swelling or support an injured limb. Check for feeling, warmth and color of the area distal to (below) the injury site, especially the fingers and toes, before and after applying the bandage. By checking both before and after bandaging, you will be able to tell if any tingling or numbness is from the bandaging or the injury. The wrap should cover a long body section, such as an arm or a calf, beginning at the point farthest from the heart. For a joint like an ankle, knee or elbow, use figure-eight turns to support the joint.

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