By S. Ortega. Northwestern State University, Louisiana. 2019.

There are a range of financial impacts for source countries that may arise for the publicly funded health care system generic robaxin 500mg visa. Costs may result from overseas cosmetic surgery or dental work that requires emergency or remedial treatment within home countries (Cheung and Wilson order 500 mg robaxin with visa, 2007 order discount robaxin, Jeevan and Armstrong generic robaxin 500mg on line, 2008, Healy, 2009). Infection outbreaks resulting from travel will also bring their own costs (cf Newman et al. Similarly, there may be health and social care costs that arise from multiple births (cf Ledger et al. But there has been little systemic collection of evidence or attempts to estimate overall system costs. There are also potential impacts on private health activity – given that they potentially lose business to overseas providers, for example cosmetic surgery. There are associated costs of patients travelling overseas – the necessity to monitor/regulate advertising and provide detailed information and advice to support potential or actual medical tourists carries its own costs. There is the likelihood that large numbers of medical tourists will impact on the source country‘s own health system, perhaps increasing trends that are encouraged by the current domestic private provision. Such flows also reduce the pressure for investment in particular facilities and technology. Indeed, there is an argument that some types of outflows of medical tourists for treatments that could be provided locally signal a failure of policy and delivery in the sender country. But it is also within higher income countries where the possibilities of a exacerbating two-tier system can emerge. If, for example, eligibility for services such as fertility or dental work is tightened, then 30 those with private resources may choose to travel overseas to maintain access (thus exercising choice and exit). Patients who are able to circumvent waiting times highlight the familiar issues of access and equity. In those countries where third-party insurers are exploring medical tourism as a provider option, those that are insured under these plans – perhaps unable to get alternative cover – may find themselves disadvantaged. Clearly, however, source-country payers may benefit from outflows of patients – including employers and employees contributing to health plans, and the public insurance system itself. There may be some opportunities for financial benefit if medical tourism is an option. Mattoo and Rathindran (2006), for example, highlight that for the United States 15 treatment that would show savings of $1. Some subsets of the population, such the Indian Diaspora, may prefer to go back ―home‖ for treatment, and may be happy to cross-subsidise some of the costs, or may not need an accompanying adult, further increasing the amount saved. Plausibly, the health systems within source countries could develop relations with off-shore medical tourism facilities to leverage cost savings – providing individuals with a choice of overseas destinations. This could also reduce waiting lists – and reflects a form of outsourcing or more ‗collective‘ medical travel (Smith et al. One of the drivers for medical tourism is price because treatments may often be available locally within the private sector, but at greater cost. There are arguments that some medical systems are inefficient and face restrictive barriers to entry. A development such as medical tourism can potentially exert competitive pressure on systems importing health care and help drive down the costs and prices offered in domestic systems (Herrick, 2007). Medical tourism may encourage economies to maximize their comparative advantage in labour costs, technology and/or capacity. We have seen in Section 4 that source counties – or those importing health services – may benefit from medical tourism through alleviating waiting lists and lowering healthcare costs, but may risk quality of care and legal liability. In this section we turn our attention to destination countries – or those exporting health services. Medical tourism has historically been from lower to higher income countries, with better medical facilities and more highly trained and qualified professionals. However, this trend is now reversing, and most recently ―hubs‖ of medical excellence have developed which attract people regionally (Horowitz et al. The main importing countries (those where the medical tourists come from) are in North America and Western Europe. Although current levels of movement are relatively limited, as outlined in Section Four , the potential, if payment was covered by third-party payers, is significant. The main exporting countries (those who provide the services to medical tourists) are located across all continents, including Latin America, Eastern Europe, Africa and Asia. For instance, Thailand and India specialise in orthopaedic and cardiac surgery, whereas Eastern European countries are hotspots for dental surgery (Smith et al. Nonetheless, many of the issues are quite generic and will affect any destination country, regardless of the level of economic development, just to a greater or lesser extent. It is also worth noting that the magnitude of the possible effects being discussed is largely unknown – in many cases the potential or actual occurrence of these effects has been observed, but the scale of effect, and how this scale may differ between countries is an unknown quantity (Smith et al. Most countries that engage in delivering care to medical tourists do so to increase the level of direct foreign exchange earnings coming into their country; to improve their balance-of-payments position (Timmermans, 2004, Ramírez de Arellano, 2007, Turner, 2007). To some extent this might be income thought of as accruing directly to the health system. For instance, in Singapore the authorities stress that involvement in medical tourism enables them to provide a broader range of clinical services to the indigenous population than would be the case if income was not being generated through medical tourism (India and Malta use such arguments) (Lee, 2010, Lee and Hung, 2010). Similarly, Ramírez de Arellano (2011) suggests that the Cuban experience is to reinvest income from foreign patients into the national system. It is therefore possible that some countries may seek foreign patients in order to develop facilities to better serve local patients (e. However, one must remember that foreign patients are merely an addition to domestic private patients; and this may be a significant or insignificant addition. There may also be different economic implications depending if these patients are simply using spare capacity or competing with domestic patients. For instance, the push by Thailand to be a hub for medical tourists in the 1990‘s was a result of the economic crisis in Asia generating a fall in domestic private patients and hence leading to spare capacity in their private sector. In this case, increasing foreign patients was more or less a net benefit to the private health system with substantial income and little real opportunity cost. However, where there is not spare capacity, and hence this capacity has to be developed, there are substantial potential costs in financial terms, but also in the wider context of fears of two-tier system developments, internal brain drain, etc. Although there may be income generated for the health sector, it is typically not health care income that concerns destination countries of course, but general increases in tourist income, since there is hoped to be a substantial level of expenditure by medical tourists, and their companions, that is not related to medical care (food, accommodation, sights, travel). Indeed, it is the promise of these earnings that often drives government involvement in investing directly or indirectly (tax incentives) in private hospitals and actively promoting medical tourism (Ramírez de Arellano, 2007, Reed, 2008, Lee, 2010). Indeed, the Indian government stated in its National Health Policy in 2002 that medical tourism was considered to be a ―deemed export‖ and therefore awarded it fiscal incentives, including lower import duties, prime land at subsidised rates and tax concessions (Garud, 2005, Ramírez de Arellano, 2007, Sengupta, 2008). Similarly, the Thai policy promoting medical tourism has been deemed to be such a success that it has recently been renewed. Thus, sectors other than medical care – especially those associated with hospitality and travel – may benefit to some degree from increased medical tourism, as will the government more centrally through increased taxation revenue. This revenue can, of course, help support the domestic public health system, for example. Nonetheless, the net income from medical tourism may not be as significant as it appears. Part of the rationale for the pursuit of medical tourists is to generate additional tourism income, which presupposes that these individuals (and their companion(s)) would not otherwise have been in the country. However, in many cases medical tourists are either Diaspora or patients who have previously visited the country and are likely to again. Thus, they are ‗regular‘ visitors who on one trip happen to ‗add in‘ an element of medical care. In this situation it is highly likely that the non-health care revenue would have been raised irrespective of their visit for medical reasons. In this situation clearly the additional income generated by the ‗medical‘ element of medical tourism is far more limited, and the overall addition to the economy consequently less, which may put a different perspective on the balance of benefits and risks. Further, there are also financial costs to be borne from inviting medical tourists into a country. As mentioned above, often there are requirements for upgraded infra-structure – either specifically within the health sector (e. However, such infrastructural investments will create favourable spillovers for non-medical tourists and the local population. There are also likely to be costs concerned with appropriate staffing of facilities, possible accreditation schemes, and other requirements to attract medial tourists.

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Another person never takes aspirin for headaches order robaxin american express, only acetaminophen generic robaxin 500 mg mastercard, because aspirin causes ringing in her ears and doesn’t seem to make the headache go away buy robaxin without prescription. The scientific evaluation of driving performance is technically and logis- tically complex order robaxin with paypal. Although more than half (56%) (12) of people who reported driving after marijuana use claimed that the drug did not affect their ability to drive, it is highly questionable whether or not individuals can assess their own driving per- formance. For ethical and safety reasons, on-the-road driving studies using “real-world” doses of drugs like cocaine and methamphetamine are not feasible. Therefore, a toxicologist must rely on a number of approaches, which may include: • Empirical Considerations:What is the pharmacology of the drug? There are advantages and disadvantages associated with each approach and these are summarized in Table 7. Collectively, these approaches can provide a toxicologist with a great deal of useful information. Taken together, the scientific literature helps determine whether the drug effects are compatible with safe driving, and specifically how they might impair a person’s ability to drive. Drugs may affect normal behavior by enhancing or impairing human performance, such as cognition or psychomotor skills. The same drug may be capable of either enhancing or impairing performance, depend- ing on the dose and pattern of drug use. Real-world doses of methamphetamine far exceed those used in the controlled studies. Epidemiological studies, as well as empirical knowledge of the drug effects at elevated dose, strongly suggest that methamphetamine can impair skills necessary for safe driving. Individuals may claim their driving ability was enhanced through drug use, so be aware of study conditions and be able to explain the relative merits and caveats. In a similar manner, studies that evaluate drug combi- nations are readily misrepresented. For example, laboratory studies have shown that a single low dose of stimulant (methamphetamine) can offset sedation caused by a depressant (alcohol). Alleviation of sedation in no way infers that a stimulant will reverse all of the impairing effects of alcohol (judg- ment, attention, psychomotor function), or vice versa. The evaluation is based upon a variety of observable signs and symptoms which are proven to be reliable indicators of drug impairment. The observations and measurements that are made by a certified Drug Recognition Expert are extremely important to the toxicologist. Clinical charac- teristics such as blood pressure, pulse, respiration, body temperature, nys- tagmus, ocular convergence (ability to cross eyes), pupil size and pupil- lary reaction to light can be useful indicators of drug use. Other observable effects, such as tremors, coordination, gait, muscle tone, perception, diaphoresis (extreme sweating), emesis (vomiting), lacrimation (excessive tearing) and appearance of the con- junctiva may also provide valuable insight (Table 2). As discussed earlier, abstinence or withdrawal syndromes resulting from chronic drug use pro- duce effects that vary considerably from those caused by acute drug intoxication (Table 3). Because many of these factors are unknown, toxicological interpretation is often difficult. Questions regarding admin- istration time can sometimes be answered using the pharmacokinetic principles, such as drug half-life. For a drug that is eliminated by first order kinetics, 99% of the drug is eliminated by seven half-lives, with less than 1% remaining in the body. Although detection times for different drugs can be estimated, these vary with dose, method of analysis and metabolic factors. Although the con- centration of a particular drug in a blood sample provides important information, it should be considered in conjunction with reports of driv- ing behavior, physiological signs and other data. The benefits and weaknesses of blood, urine and saliva samples are described below: Blood Advantages: • A drug that is circulating in the blood may bind to receptors in the brain. Therefore, a blood sample that contains a drug is more likely to indicate recent usage compared to a urine sample. In the absence of other information, a urinary metabolite reported as “present” may have limit- ed significance when trying to determine whether the individual was impaired. The relative acidity or alka- linity of the urine can determine how quickly a particular drug is eliminated from the urine. However, urine drug results may be useful in determining an approximate time frame during which drug expo- sure took place. For example, the heroin metabolite 6-acetylmorphine is detectable in urine for approximately 2-8 hours after ingestion. Disadvantages: • Some pharmacological interpretation may be possible but there is lim- ited reference data at present. Therefore, the presence of elevated levels of cocaine in a blood sample may also indicate moderately recent use. The characterization of certain, specific concentrations of drugs in blood as therapeutic, toxic or lethal is often useful, but must be assigned with caution due to inter-individual differences. These ranges overlap for some drugs, making it difficult to classify the concentration in this way. Even low or sub-clinical concentrations of some drugs in blood are associated with impaired driv- ing. Following chronic use of a stimulant drug like methamphetamine or cocaine, an individual may experience extreme fatigue and exhaustion, consistent with the “crash” phase of drug use, sometimes called the “down- side. Thus, toxicological interpretation is usually based upon a combination of toxi- cological analyses, case information, and field observations made by law enforcement personnel or clinicians who may have had contact with the individual. Multiple drug use can complicate interpretation, so drug combinations need to be examined in terms of their ability to interact with each other and produce additive, synergistic or antagonistic effects: • Additive effects occur when a combination of drugs produce a total effect that is equal to the sum of the individual effects • Synergistic effects occur when a combination of drugs produce a total effect that is greater than the sum of the individual effects • Antagonistic effects occur when the effect of one drug is lessened due to the presence of another drug A trained toxicologist will be familiar with the types of drugs that can have additive, synergistic or antagonistic effects. Interpretation of toxicology results is compounded by a number of fac- tors which includes, but is not limited to multiple drug use, history of drug use (chronic vs. The same dose of drug given to two individuals may possibly produce similar effects but with varying degrees of severity that elicits a different response. The presence of a drug alone in a person’s blood or urine does not necessarily mean that he or she was impaired. Based on a com- bination of these factors (Figure 2) it is often possible for a toxicologist to provide expert testimony regarding the consistency of this information with driving impairment. Initially, samples are screened for common drugs or classes of drugs using an antibody-based test. Samples that screen positive are then re-tested using a second, more rigorous technique, usually called confirmation. Confirmatory Tests Assume for a moment that you have in your hand a key ring with ten keys, all made of brass, all appearing to have the same cut. A few of those will fit in the lock (screening test with false positives since the keys are structurally similar to each other) but only one will actually turn and unlock the door (confirmation test). Screening Tests An immunoassay test is the most common type of screening test for drugs of abuse. Using this type of test, a drug or metabolite in a biological sam- ple can be tentatively identified using an anti-drug antibody. If a drug is present in the sample, the anti-drug antibody will bind to it; if no drug is present in the sample, the anti-drug antibody will not bind to the sam- ple. Various methodologies and detection methods are utilized, giving rise to a number of immunoassays. Immunoassay test results are considered presumptive, not conclusive, because the antibodies that are used may cross-react with other substances to varying degrees, resulting in false positive results. Analogs or substances that are structurally similar to the drug are most likely to produce a false positive. Most laboratories utilize screening tests only to determine which drugs or classes of drugs might be indicated. This allows confirmatory tests to be performed for the drugs indicated by the immunoassay. Since it is unfeasible to test every sample for every drug using confirmatory proto- cols, screening tests are used principally to determine where to focus analytical resources in the laboratory. Cut-offs The immunoassay test will have a cut-off value or threshold concentra- tion, above which a sample is considered positive. This is because workplace drug testing cut-offs in urine are set so that inadvertent drug exposure (e.

Continued use will be contingent upon demonstrated improvement in analgesia buy discount robaxin 500 mg on-line, physical function and quality of life – and absence of significant adverse events and maladaptive behaviors order robaxin 500 mg otc. Consultation as needed: Consultation with a Pain Medicine or other specialist may be warranted cheap 500mg robaxin amex, depending on the expertise of the practitioner and the complexity of the presenting problem order 500mg robaxin free shipping. The management of pain in patients with a history of addiction or a comorbid psychiatric disorder requires special consideration. Periodic review of treatment efficacy: Review of treatment efficacy should occur frequently to assess the functional status of the patient, continued analgesia, adverse effects, quality of life, and indications of medication misuse. Monitoring of compliance is a critical aspect of chronic opioid prescribing, using such tools as random urine drug screening, pill counts, and where available, review of prescription monitoring data base reports. Close follow-up and reexamination is warranted to assess the nature of the pain complaint and to ensure that opioid therapy is still indicated. Attention should be given to the possibility of a decrease in global function or quality of life as a result of opioid use. Documentation: Documentation is essential for supporting the evaluation, the reason for opioid prescribing, the overall pain management treatment plan, any consultations received, and periodic review of the status of the patient. Keywords Abstract diagnosis; drug allergy; drug Skin tests are of paramount importance for the evaluation of drug hypersensitiv- hypersensitivity; intradermal test; skin test. Drug skin tests are often not carried out because of lack of concise Correspondence information on specific test concentrations. Knut Brockow, Department of based on history alone, which is an unreliable indicator of true hypersensitiv- Dermatology and Allergology Biederstein, ity. To promote and standardize reproducible skin testing with safe and nonirri- Technische Universitat Munchen,€ € tant drug concentrations in the clinical practice, the European Network and Biedersteiner Str. Group on Drug Allergy has performed a literature search on skin test drug con- Tel. Where the literature is poor, we have taken into consideration Accepted for publication 7 February 2013 the collective experience of the group. We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. For many other drugs, Edited by: Hans-Uwe Simon there is insufficient evidence to recommend appropriate drug concentration. Skin test concentrations for drugs is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hyper- sensitivity. Additional articles patients and is associated with significant morbidity and were found through archives or on the reference lists of the mortality (1). Further data sources were textbooks, test specific immune mechanisms are classified as drug allergy. The mecha- We restricted the search to systemically administered drugs nism underlying the former is thought to be IgE-mediated and excluded topically applied agents causing only contact or and the latter is primarily T cell-mediated. In drug allergy, skin testing is the most the group, when other reliable data were lacking. The litera- widely used method to determine sensitization, as other tests ture reviewed contained minimal data on testing of healthy (in vitro or drug provocation test) are less specific, less sensi- controls. There is no international con- sensus on how skin tests with drugs should be performed or Data extraction interpreted. There have been no multicentre studies to estab- lish drug concentration, test protocol, specificity, sensitivity Our aim has been to provide data for all widely used drugs and safety. Members of the task force were assigned centrations for the diagnosis of drug hypersensitivity are not different drug classes (Appendix 1) who retrieved identified available for most drugs (3). The relevance of articles was not investigate drug reactions and rely on the history alone evaluated by the responsible authors on the basis of title to make a diagnosis of drug allergy and the unjustified use/ and abstract. For drug groups provocation tests (5), as well as recommendations for the where evidence was considered sufficient for recommenda- management of betalactam hypersensitivity (6), perioperative tions to be made on skin concentrations, tables are included anaphylaxis (7), radiocontrast media reactions (8), hypersen- in the following text (Tables 1–3). It is the primary purpose of this paper to present skin test The submission of the responsible author(s) was discussed concentrations for practical use by the allergist. Suggested by the task force, confirmed or amended by consensus of concentrations should be nonirritating aiming for the highest the group. By evaluating the liter- ature, we developed additional key statements and recom- mendations concerning methodology and clinical value of skin testing for various drug classes. Published by John Wiley & Sons Ltd 703 Skin test concentrations for drugs Brockow et al. These tend to occur within 1 h after drug administra- recommendation for key statements and skin test concentra- tion, but may develop after 1–6 h (and exceptionally later). Evidence was graded as high quality, if further oedema and may progress in some cases to more severe research is very unlikely to change our confidence in the symptoms of bronchospasm, hypotension and anaphylactic estimate of effect; moderate, if further research is likely to shock. Nonimmediate hypersensi- of effect and may change the estimate; low, if further tivity reactions develop within hours to days but in highly research is very likely to have an important impact on our sensitized individuals may manifest within 24 h. A validated protocol should be used, and guidelines have A recommendation is weak if the benefits and risks are been published (high/strong) (2, 12). Scratch tests are poorly finely balanced, or appreciable uncertainty exists about the standardized and are not recommended (moderate/strong). The grading of high/strong in the For children, the tools used for management established in text denotes a high quality of evidence and strong strength adults are applicable even though there is insufficient evi- of recommendation. The sensitivity of skin tests appears to be moderate to high Results for immediate hypersensitivity reactions to betalactam antibiot- ics, perioperative drugs, heparins, platinum salts, radiocontrast General aspects media, but low for many other drugs (moderate/weak). Skin test is the most commonly used procedure to confirm a The parenteral preparation of the suspected drug, prefera- sensitization in drug hypersensitivity; for many drugs, in vitro bly the intravenous form at the recommended concentration, tests are not available or sufficiently validated (high/strong). For drugs suspected of 704 Allergy 68 (2013) 702–712 © 2013 John Wiley & Sons A/S. Skin test concentrations for drugs Table 3 Nonirritating test concentrations for selected other drugs able to make the test as sensitive as possible (12). Most drugs and drug classes are poorly soluble in water, and it is often the saturated sus- pension that is used. This will facili- Heparinoids† Undiluted 1/10 diluted Undiluted tate comparative/standardize studies (high/strong). Drugs may be irritant to the skin, and it Biologicals is necessary to establish in healthy controls (ideally! The negative predictive value is dependent Methylene blue 1/100 diluted on the pretest probability and is not helpful without this infor- Fluorescein Undiluted 1/10 diluted Undiluted mation in selected patient groups. This can be established using different dilutions of cially when parents report their children’s history (high/ increasing drug concentration. Initially, specific IgE is determined for confirma- tration should ideally be established in healthy controls tion. Where the drug is available only in tablet, method for confirming betalactam allergy. Published by John Wiley & Sons Ltd 705 Skin test concentrations for drugs Brockow et al. Positive skin and/or laboratory tests may be seen in up to As with penicillins, skin tests with nonirritant concentra- 40% of patients with immediate hypersensitivity reactions to tion of cephalosporins have a higher sensitivity compared pyrazolones (high/strong) (28). Concentrations up to 30% may be toler- the risk provoking systemic symptoms (high/strong) (6). When the skin test is point titration) are used when investigating immediate hyper- negative, a diagnosis cannot be established without a drug sensitivity reactions (high/strong). The value of skin tests with opioids remains unproven, and For most nonbetalactam antibiotics, the value of skin tests optimal skin test concentrations are unknown (moderate/ appears to be uncertain (moderate/weak) and false-positive strong) (31). For fentanyl and its derivatives, the undiluted reactions may occur when the antibiotic is tested at high con- solution is recommended (Table 2) (moderate/strong), and centrations. There is no universal agreement on the optimal possible, and concentrations used in the literature are given in vehicle (aqua, petrolatum, ethanol) or test concentration Table S1 (26, 27). There appears to be skin test cross-reactivity between morphine and 5% codeine phosphate but not with Nonsteroidal anti-inflammatory drugs 5% pentazocine and 5% tramadol (low/weak). There have been numerous multicentre studies To diagnose these reactions, bisulphite skin tests are of no from France under the auspices of Societe Francaise d’anes- diagnostic value and oral provocation test with metab- thesia et de Reanimation (34), whose recommendations have isulphite is necessary to confirm/exclude the diagnosis been updated recently (7) and these have been endorsed by (moderate/strong). Intradermal test using 1/10 dilution erative screening or testing in patients without prior reactions appears irritant (41). If 1/10 dilution has been used, it is may lead to false-positive tests/conclusions and should not be advised that further tests be carried out with 1/100 and 1/ carried out routinely (high/strong). It is recommended that in the investigation of the sus- tion of heparins (low/weak). Chlorhexidine is an integral part of the treatment is continued, there is a risk of a generalized eczema perioperative test panel in some centres.

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