By Y. Cruz. Humboldt State University.

Sustainability considerations Prior to equipment acquisition cheap sildalis 120mg mastercard, facilities should ensure buy 120mg sildalis with visa, through appropriate budgeting, that there is adequate and properly trained staff for its operation and that the equipment can be maintained during its projected lifetime. If the equipment is technically complex, it may be less expensive to outsource maintenance services than to train local maintenance personnel. Discarding the equipment at the end of its life cycle should also be contemplated and disposal costs budgeted. Obtaining authorization from the regulatory authorities Facilities of countries with radiation protection legislation/regulations need to seek approval of the regulatory authority before acquiring radiological equipment. The authorization process may require registering the equipment or licensing the installation [3]. Most refurbishing companies will not sell any piece of equipment to a foreign country until such documentation is produced. Facilities which plan to introduce new practices will need to produce more documentation than facilities which only replace a unit and usually require permits from other governmental entities such as the ministry of health, which regulates medical practices. In facilities of countries which do not have any radiation safety legislation, it is the responsibility of the facility manager to ensure that the equipment and its use comply with international safety standards. The compliance should be documented in writing and be made available to the staff and to the patients and public, if required. Site preparation Good coordination should exist between equipment acquisition and site preparation. The room in which the equipment is to be housed needs to be ready before the equipment arrives, so that its installation can proceed smoothly. Clearing customs If the equipment comes from a foreign country, import permits are required. The facility manager must ensure that the documentation required in customs clearing processes is ready well before the equipment arrives. Installation Arrangements for installation, including the need for cranes and other heavy machinery, should be made in advance of radiological equipment arrival. Contractors and local staff must be properly protected and monitored if they can be exposed to ionizing radiation during their work, for example when a cobalt source is exchanged. Acceptance testing Acceptance testing is the process of determining whether the unit meets acquisition specifications. Acceptance tests are normally done between a person of the institution (preferably a medical physicist) and an engineer or technical representative of the manufacturer. For second hand equipment, compliance with the original manufacturer’s specifications can be tricky, unless it has been specified in the acquisition agreement. Previous service records should be examined in detail, and repaired or replaced components should be tested very carefully to assess whether they may compromise safety. Adjustment costs may have to be borne by the user, unless clearly indicated in the acquisition agreement that the responsibility is the institution’s or the company’s providing the equipment. Consumables, such as X ray film or printing paper, should be available at acceptance testing, to ensure that the tests can be performed and documented. Commissioning Commissioning is the process in which the necessary clinical data are acquired so that the unit can be used clinically. If so, these data should be consulted and verified before allowing patient examinations or treatments. Verification should be performed by a knowledgeable and competent medical physicist and should be more or less extensive depending on the complexity of the equipment. Establishment of quality control/quality assurance programmes Based on the acceptance testing and on the acquired data during commissioning, it is important to develop a set of tests and establish compliance criteria to check that the unit continues to perform adequately. The institution’s medical physicist should assume responsibility that the unit always functions within the established tolerances. Specific attention was given to: (i) the situation in developing countries, where access to proper imaging must be improved; (ii) the fact that training in diagnostic imaging and radiation protection is part of the safety culture; and (iii) the need to normalize education requirements for radiation, which is a high priority. The areas covered were the need for dose reduction as a result of standardized quality assurance procedures, education and training, and the development and implementation of a sustainable safety culture, research needs to improve the knowledge in individual radiosensitivity of patients, as well as the access to proper imaging techniques and training in diagnostic imaging and radiation protection in developing countries. Integration of radiation protection and safety It is important to include radiation protection and safety plans in management control systems in hospitals. This can best be achieved by involvement of key managers, authority given to radiation protection experts and transparent internal audits. Key challenges within such a process include effective communication within the organization and adoption of a graded approach towards radiation and safety. Dose assessment and national registries It is important to assess effective collective doses from diagnostic X ray and nuclear medicine examinations. This can be best achieved by establishing national registration systems to monitor frequency and doses, with the aim of identifying long term trends. The results can be used to select priorities for clinical audit and optimization actions.

The experience of such an unpleasant bolism of many medications by acti- Glutathione is an antioxidant safe sildalis 120mg, an reaction discount sildalis 120 mg on-line, or even the expectation that vating cytochrome P450 enzymes in agent that prevents certain highly reac- this reaction will occur if alcohol is con- the liver, alcohol and its metabolism tive, oxygen-containing molecules (i. Thus, alcohol metabolism and the metabolism of certain medi- with disulfiram; however, many other affects the liver’s redox state and glu- cations can generate reactive oxygen medications (and certain toxic sub- tathione levels. The term “redox state” species, thereby inducing a state called stances) also can induce disulfiram-like refers to the concentrations of two oxidative stress in the cells. At the same reactions when combined with alcohol substances in the cells— nicotinamide time, heavy alcohol consumption (see table 2). For example, such interactions Sulfisoxazole Pediazole can occur in people who consume alco- hol with a meal shortly before or after Cardiovascular medications Isosorbide dinitrate Dilatrate, Isordil, Sorbitrate taking a medication or who take pain (nitrates) Nitroglycerin Nitro-Bid, Nitrostat medications after drinking to prevent a hangover. Alcohol-medication inter- Diabetes medications Chlorpropamide Diabinese actions fall into two general categories: (sulfonylureas) Glyburide DiaBeta, Glynase, Micronase Tolazamide generic pharmacokinetic and pharmacodynamic. Tolbutamide generic Pharmacokinetic interactions are those in which the presence of alcohol directly Vol. Antibiotics Erythromycin various Rx •Erythromycin may increase gastric emptying, (microbial infections) Isoniazid Nydrazid, leading to faster alcohol absorption in the Rifamate, Rifater small intestine. Anticonvulsants Phenytoin Dilantin Rx •Chronic alcohol consumption induces (seizure disorders) phenytoin breakdown. Hydroxyzine Atarax, Vistaril •The interactions are more pronounced in Promethazine Phenergan elderly people. Cyproheptadine Periactin •No documented interactions exist with nonsedating antihistamines (i. Anticoagulants Warfarin Coumadin Rx •Acute alcohol intake may increase anticoagulation (prevention of blood clots) by decreasing warfarin metabolism; chronic alcohol ingestion decreases anticoagulation by increasing warfarin metabolism. Antidiabetic agents Chlorpropamide Diabinese Rx •Alcohol consumption by diabetic patients taking (blood sugar Glipizide Glucotrol these medications increases the risk of lower- regulation) Glyburide DiaBeta, Glynase, than-normal blood sugar levels (i. Micronase •Chlorpropamide, glyburide, and tolbutamide can Tolbutamide Orinase cause disulfiram-like interactions after alcohol Metformin Glucophage ingestion. Barbiturates Phenobarbital various Rx •Chronic alcohol intake increases barbiturate (anesthesia, pain relief) metabolism by cytochrome P450. Muscle relaxants Carisoprodol Soma Rx •Alcohol consumption enhances impairment Cyclobenzaprine Flexeril of physical abilities (e. Tricyclic Amitriptyline Elavil, Endep Rx •Alcohol consumption increases the risk of antidepressants Clomipramine Anafranil sedation and a sudden drop in blood (depression) Desipramine Norpramin pressure when a person stands up (i. This interference of alcohol-medication interactions in ing that heavy alcohol use can impair can take two forms, as follows: moderate drinkers may differ, however, the function of certain immune cells between pharmacokinetic and pharma- and that alcoholics are predisposed to • The breakdown and excretion of codynamic interactions. These effects, how- the affected medications are of potential pharmacokinetic interac- ever, are unlikely to occur in moder- delayed, because the medications tions with alcohol is great, because the ate drinkers. These classes differ in • The metabolism of the affected exists even after low alcohol consump- their mechanism of action in that medications is accelerated, because tion, researchers have not yet demon- they affect different brain chemicals. W hen alcohol is not pre- Conversely, pharmacodynamic inter- stimulating activity. Accordingly, line, doxepin, maprotiline, and elimination rate for medications that those interactions clearly pertain to trimipramine) will cause the most these enzymes metabolize. In this type these warnings is not entirely clear, first-pass metabolism of amitriptyline of interaction, which occurs most however, because only a few antibi- in the liver, resulting in increased ami- commonly in the central nervous sys- otics appear to interact with alcohol. These interactions may be should abstain from alcohol, because paroxetine, and sertraline), which are synergistic— that is, the effects of the isoniazid can cause liver damage, currently the most widely used anti- combined medications exceed the sum which may be exacerbated by daily depressants, are much less sedating of the effects of the individual medica- alcohol consumption. Conversely, tidine and ranitidine have the most loratidine) have been developed to barbiturates increase total cytochrome pronounced effect, nizatidine has an minimize drowsiness and sedation P450 activity in the liver and accelerate intermediate effect, and famotidine while still providing effective allergy alcohol elimination from the blood appears to have no effect (i. These medications are biturates, concurrent consumption of may produce a certain narcotic-like sedative or sleep-inducing (i. For example, carisoprodol is probably the most commonly pre- It is worth noting that both barbitu- is a commonly abused and readily scribed barbiturate in modern prac- rates and benzodiazepines can impair available prescription medication that tice, also is used in the treatment of memory, as can alcohol. In fact, this pharmacodynamic interactions between effect sometimes is exploited by mix- 5 Another class of medications, which prevent gastric the two substances. Acetaminophen break- provide “hidden” doses of acetamin- creating a quick state of euphoria. In addition, patients generally should not exceed should not take regular acetaminophen arthritis and other disorders of the mus- the maximum doses recommended by in addition to the combination product). This excessive trointestinal bleeding in elderly should be aware that combination warfarin activity results from alcohol- people. Alcohol may exacerbate cough, cold, and flu medications may related inhibition of warfarin metab- that risk by enhancing the ability contain aspirin, acetaminophen, or olism by cytochrome P450 in the liver of these medications to damage the ibuprofen, all of which might con- (Lieber 1994). Alcohol accentuates required to achieve the desired antico- to be enhanced by concurrent alco- the opioids’ sedating effects.

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Were patients similar for demo- graphics order sildalis 120mg with visa, severity sildalis 120mg with visa, co-morbidity, and other prognostic factors? There is an excellent article by Hanley and Lippman- Hand that shows how to handle this eventuality. The maximum number of events that can be expected to occur when none have been observed is 3/n. One could expect to see as many as one adverse event in every 5 patients and still have come up with no events in the 14 patients in the initial study. The probability of no adverse events in one patient is 1 minus the probability of at least one adverse event in one patient. Another way of writing this is p(no adverse event in one patient) = 1–p(at least one adverse event in one patient). We can continue to reduce the actual adverse event rate to 1:10, and using the same process we get p(no adverse events in 14 patients) = (0. For example, studies of head-injured patients to date have shown that none of the 2700 low-risk patients, those with laceration only or bump without loss of consciousness, headache, vomiting, or change in neurological status, had any intracranial bleeding or swelling. Therefore, the largest risk of intracranial injury in these low-risk patients would be 3/2700 = 1/900 = 0. General observations on the nature of risk Most people don’t know how to make reasonable judgments about the nature of risk, even in terms of risks that they know they are exposed to. This was articu- lated in 1662 by the Port Royal monks in their treatise about the nature of risk. There 154 Essential Evidence-Based Medicine Table 13. People are more likely to risk a poor outcome if due to voluntary action rather than imposed action. They are likely to smoke and accept the associated risks because they think it is their choice rather than an addiction. Similarly, they will accept risks that they feel they have control over rather than risks controlled by others. Because of this, people are much more likely to be very upset when they find out that their medication causes a very uncommon, but previously known, side effect. One only has to read the newspapers to know that there are more stories on the front page about catastrophic accidents like plane crashes or fatal automo- bile accidents than minor automobile accidents. Patients are more willing to accept the risk of death from cancer or sudden cardiac death than death due to unforeseen complications of routine surgery. If there is a clear benefit to avoiding a particular risk, for example that one shouldn’t drink poison, patients are more likely to accept a bad outcome if they engage in that risky behavior. A major exception to this rule is cigarette smoking, because of the social nature of smoking and the addictive nature of nicotine. They are more willing to accept risk that is distributed to all people rather than risk that is biased to some people. There is a perception that man-made objects ought not to fail, while if there is a natu- ral disaster it is God’s will. Risk that is generated by someone in a position of Risk assessment 155 trust such as a doctor is less acceptable than that generated by someone not in that position like one’s neighbor. We are more accepting of risks that are likely to affect adults than of those primarily affecting children, risks that are more familiar over those that are more exotic, and random events like being struck by lightning rather than catastrophes such as a storm without adequate warning. Irving Fisher, Professor of Economics, Yale University, 1929 Learning objectives In this chapter you will learn: r the essential features of multivariate analysis r the different types of multivariate analysis r the limitations of multivariate analysis r the concept of propensity scoring r the Yule–Simpson paradox Studies of risk often look at situations where there are multiple risk factors asso- ciated with a single outcome, which makes it hard to determine whether a sin- gle statistically significant result is a chance occurrence or a true association between cause and effect. Since most studies of risk are observational rather than interventional studies, confounding variables are a significant problem. Multivari- ate analysis and propensity scores are methods of evaluating data to determine the strength of any one of multiple associations uncovered in a study. They are attempts to reduce the influence of confounding variables on the study results. Multivariate analysis answers the question “What is the importance of one risk factor for the risk of a disease, when controlling for all other risk factors that could contribute to that disease? For example, in a study of lipid levels and the risk for coronary-artery disease, it was found that after adjusting for advancing age, 156 Adjustment and multivariate analysis 157 smoking, elevated systolic blood pressure, and other factors, there was a 19% decrease in coronary heart disease risk for each 8% decrease in total cholesterol level. In studies of diseases with multiple etiologies, the dependent variable can be affected by multiple independent variables. Smoking, advancing age, ele- vated systolic blood pressure, other factors, and cholesterol levels are the inde- pendent variables. The process of multivariate analysis looks at the changes in magnitude of risk associated with each independent variable when all the other contributing independent variables are held fixed.

In order to draw conclusions from this study generic sildalis 120mg, patient exposure to the risk factor being studied must continue until the outcome occurs discount 120mg sildalis with visa. If the exposure began long before the outcome occurs and is intermittent, it will be more difficult to associate the two. If done properly, cross-sectional studies are capable of calculating the prevalence of disease in the population. Prevalence is the percentage of people in the population with the outcome of interest at any point in time. Since all the cases are looked at in one instant of time, cross-sectional studies cannot calculate incidence, the rate of appearance of new cases over time. Another strength of cross-sectional stud- ies is that they are ideal study designs for studying the operating characteristics of diagnostic tests. We compare the test being studied to the “gold standard” test in a cross-section of patients for whom the test might be used. The trade-off to the ease of this type of study is that the rules of cause and effect for contributory cause cannot be fulfilled. Since the risk factor and outcome are measured at the same time, you cannot be certain which is the cause and which the effect. A cross-sectional study found that teenagers who smoked early in life were more likely to become anxious and depressed as adults than those who began smoking at a later age. Does teenage smoking cause anxiety and depres- sion in later years, or are those who have subclinical anxiety or depression more likely to smoke at an early age? It is impossible to tell if the cause preceded the effect, the effect was responsible for the cause, or both are related to an unknown third factor called a confounding or surrogate variable. Confounding or surro- gate variables are more likely to apply if the time from the cause to the effect is short. For example, it is very common for people to visit their doctor just before their death. The visit to the doctor is not a risk factor for death but is a “surro- gate” marker for severe and potentially life-threatening illness. These patients visit their doctors for symptoms associated with their impending deaths. Prevalence– incidence bias is defined as a situation when the element that seems to cause an outcome is really an effect of or associated with that cause. This occurs when a risk factor is strongly associated with a disease and is thought to occur before 60 Essential Evidence-Based Medicine the disease occurs. Thus the risk factor appears to cause the disease when in reality it simply affects the duration or prognosis of the disease. The antigen was not a risk factor for the disease but an indicator of good prognosis. Longitudinal studies Longitudinal study is a catchall term describing either observations or interven- tions made over a given period of time. There are three basic longitudinal study designs: case–control studies, cohort studies, and clinical trials. These are ana- lytic or inferential studies, meaning that they look for a statistical association between risk factors and outcomes. Case–control studies These studies were previously called retrospective studies, but looking at data in hindsight is not the only attribute of a case–control study. There is another unique feature that should be used to identify a case–control study. The sub- jects are initially selected because they either have the outcome of interest – cases – or do not have the outcome of interest – controls. They are grouped at the start of the study by the presence or absence of the outcome, or in other words, are grouped as either cases or controls. This type of study is good to screen for potential risk factors of disease by reviewing elements that occurred in the past and comparing the outcomes. The ratio between cases and controls is arbitrar- ily set rather than reflecting their true ratio in the general population The study then examines the odds of exposure to the risk factor among the cases and com- pares this to the odds of exposure among the controls. The strengths of case–control studies are that they are relatively easy, cheap, and quick to do from previously available data. They can be done using current patients and asking them about events that occurred in the past. They are well suited for studying rare diseases since the study begins with subjects who already have the outcome. Each case patient may then be matched up with one or more suitable control patients. Ideally the controls are as similar to the cases as pos- sible except for the outcome and then their degree of exposure to the risk fac- tor of interest can be calculated. Case–controls are good exploratory studies and can look at many risk factors for one outcome.

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