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When the indications are followed cautiously, Incidence of gastrointestinal haemorrhage the risk of bleeding is smaller than the risk of thrombosis and the prescription Gastrointestinal bleeding represents a se of antiplatelet or anticoagulant therapy is rious medical condition, with mortality considered safe and necessary. However, reaching 10%, and one that contributes the risk of a bleeding episode from the to increased health costs worldwide. Pipilis et al incidence of gastrointestinal bleeding is estimated replace the well studied clopidogrel are prasugrel at 100-200 cases per 100,000 general population per and ticagrelor, both already in everyday clinical use. Both are stronger antiplatelet agents and are there the ratio of upper to lower gastrointestinal bleeding fore related to more haemorrhages from the gas is approximately 4-5 to 1, but in the elderly the ratio trointestinal system when compared with clopido 10-12 becomes smaller as diseases of the colon (diverticu grel. In fact, the existing guidelines for the man losis, angiodysplasia, neoplasms) become more fre agement of patients with acute coronary syndromes 7 quent. Mortality remains around while for ticagrelor versus clopidogrel the respective 10% for upper gastrointestinal and around 2-4% for numbers are 22 and 6. For the main indications of anticoagulant thera Any treatment with classical or novel antithrom py, such as atrial fibrillation and a mechanical heart botic drugs is expected to increase the risk of gastro valve, the benefit of reducing thromboembolic com intestinal bleeding. In general, the annual risk of major bleed mary prevention, however, the use of aspirin remains ing with warfarin is estimated at 2-3% and depends controversial and is probably not indicated (unless on the presence of several risk fac to rs (as will be dis there is a very high cardiovascular risk) because of the cussed later). In the collabora in patients with atrial fibrillation are from the gastro 14 tive meta-analysis of the antiplatelet therapy trialists, intestinal system. In cardial infarctions and one vascular death, at a cost comparison with warfarin, rivaroxaban at a dose of of 3 major bleeding episodes (most of which are from 20 mg once daily and dabigatran at a dose of 150 mg 8 the gastrointestinal tract). There is undoubtedly an twice daily increase gastrointestinal bleeding in gen unfavourable benefit- to -risk ratio. Apixaban probably does not in new cardiovascular events at a cost of 10 additional crease gastrointestinal bleeding when compared with 19 major bleeding episodes (1/3 of which were from the warfarin. Here, the benefit- to -risk ratio ed in more gastrointestinal bleeds in comparison with is considered acceptable; thus, dual antiplatelet ther warfarin, while the smaller dose of 30 mg was safer in apy is the established antithrombotic regime follow terms of bleeding but less effective in preventing isch 20 ing an acute coronary syndrome or the implantation aemic strokes. It should be not Risk fac to rs for bleeding from antiplatelets and ed that different antithrombotic strategies were com anticoagulants pared and each study had a different population of patients with different baseline characteristics (for the main risk fac to rs favouring the occurrence of example, the patients in the studies of atrial fibril gastrointestinal bleeding are the presence of an un lation were 8-10 years older than those in the stud derlying pathology, older age, renal dysfunction, a ies of coronary artery disease). As stated earlier, the his to ry of haemorrhage, and the prescription of an newer, more potent antiplatelet drugs (prasugrel and tithrombotic therapy. Peptic ulcer is the most com ticagrelor) increase bleeding when compared with mon cause of upper gastrointestinal bleeding (50% clopidogrel. Dabigatran, rivaroxaban and edoxaban, in older series, but around 33% in more recent ones). Major gastrointestinal haemorrhages in trials of different antithrombotic therapies. Study Indication Duration Antithrombotic Incidence of therapies gastrointestinal bleeding among the compared groups fifiC8 Myocardial infarction 2 years Usual vs. In patients with atrial Lower gastrointestinal bleeding (data from vari fibrillation, several scoring systems have been pro ous series of patients) is due to diverticulosis (30 posed to calculate bleeding risk. These scores address 40%), haemorrhoids (5-14%), angiodysplasia or isch bleeding risk in general and are not specific for the aemic vascular disease (10-37%), inflamma to ry dis gastrointestinal tract. Still, they are relevant because ease (9-18%), cancer/polyp (10-14%), or other rarer the majority of bleeding episodes are, indeed, local 30,31 causes. A daily dose of 300 mg haemorrhagic complications, but it must be empha doubles the risk in comparison with a dose of 100 sised that, very frequently, bleeding can occur with 32 36,37 mg. Enteric-coated aspi rin seems to bear a smaller risk for blood loss when Parameters relevant to the re-initiation of antithrombotic compared with plain aspirin, although this matter is 33,34 therapy controversial. Coadministration of a second anti platelet agent with aspirin increases the risk signifi the management of the bleeding episode is beyond cantly (as explained earlier). Of course, discontinuing the with adjustment for multiple risk fac to rs, it was found antithrombotic treatment is important but the rever that the relative risk for upper gastrointestinal bleed sal of the antithrombotic effect of any drug is prob ing was 3. However, re when the dose of aspirin was 300 mg, 100-300 mg and versal may be delayed, followed frequently by a pro 9 thrombotic situation, and carries a risk of adverse re <100 mg, respectively. The most widely effect of rivaroxaban, but data are limited to healthy used is the Rockall score, which combines clinical and volunteers rather than patients with active haemor labora to ry findings. Once haemostasis is secure, the clinical ques bleeding after haemostasis and mortality. Patients tion for the treating physician is if, when, and how with a Rockall score <2 are considered at low risk the antithrombotic therapy should be restarted. The for recurrence and patients with a score >8 have high 41 main parameters to take in to consideration are the mortality (Table 3). After day 7, the recurrences 42 the thromboembolic risk exceeds the risk of recurrent were rare.

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Nevertheless, despite improvement in the technology of diagnostic ultrasound, the recognition of these anomalies remains difficult. Referral centers with special expertise in fetal echocardiography have indeed reported both false positive and false negative diagnoses. There is a typical association between conotruncal anomalies and 22q11 deletion, a condition associated with long term implications, including immune deficits, neurological development and speech, that may not be apparent in neonatal life. Associated cardiac lesions are present in about 50% of cases, including ventricular septal defects (which can occur anywhere in the ventricular septum), pulmonary stenosis, unbalanced ventricular size ("complex transpositions"), anomalies of the mitral valve, which can be straddling or overriding. There are three types of complete transposition: those with intact ventricular septum with or without pulmonary stenosis, those with ventricular septal defects and those with ventricular septal defect and pulmonary stenosis. Diagnosis Complete transposition is probably one of the most difficult cardiac lesions to recognize in utero. In most cases the four-chamber view is normal, and the cardiac cavities and the vessels have normal appearance. The most useful echocardiographic view however is the left heart view demonstrating that the vessel connected to the left ventricle has a posterior course and bifurcates in to the two pulmonary arteries. Difficulties may arise in the case of huge malalignment ventricular septal defect with overriding of the posterior semilunar root. This combination makes the differentiation with double outlet right ventricle very difficult. The left atrium is connected to the right ventricle, which is in turn connected to the ascending aorta. Conversely, the right atrium is connected with the right ventricle, which is in turn connected to the ascending aorta. The derangement of the conduction tissue secondary to malalignment of the atrial and ventricular septa may result in dysrhythmias, namely complete atrioventricular block. For diagnostic purposes, the identification of the peculiar difference of ventricular morphology (modera to r band, papillary muscles, insertion of the atrioventricular valves) has a prominent role. Demonstration that the pulmonary veins are connected to an atrium which is in turn connected with a ventricle that has the modera to r band at the apex is an important clue, that is furthermore potentially identifiable even in a simple four-chamber view. Clinical presentation may be delayed up to 2-4 weeks, and usually occurs with signs of congestive heart failure. Surgery (which involves arterial switch to establish ana to mic and physiological correction) is usually carried out within the first two weeks of life. Operative mortality is about 10% and 10-year follow-up studies report normal function but there is uncertainty if in the long term such patients are at increased risk of atherosclerotic coronary disease. Tetralogy of Fallot can be associated with other specific cardiac malformations, defining peculiar entities. Hypertrophy of the right ventricle, one of the classic elements of the tetrad, is always absent in the fetus, and only develops after birth. Diagnosis Echocardiographic diagnosis of tetralogy of Fallot relies on the demonstration of a ventricular septal defect in the outlet portion of the septum and an overriding aorta. Conversely, demonstration with color and/or pulsed Doppler that, in the pulmonary artery, there is either no forward flow or reverse flow allows a diagnosis of pulmonary atresia. In cases with minor forms of right outflow obstruction and aortic overriding differentiation from a simple ventricular septal defect can be difficult. Incorrect orientation of the transducer may demonstrate apparent sep to -aortic discontinuity in a normal fetus. The mechanism of the artifact is probably related to the angle of incidence of the sound beam. Abnormal enlargement of the right ventricle, main pulmonary trunk and artery, suggests absence of pulmonary valve. Evaluation of other variables, such as multiple ventricular septal defects and coronary anomalies, would be valuable for a better prediction of surgical timing and operative prognosis. Even in cases of tight pulmonary stenosis or atresia, the wide ventricular septal defect provides adequate combined ventricular output, while the pulmonary vascular bed is supplied in a retrograde manner by the ductus. The only exception to this rule is represented by cases with an absent pulmonary valve that may result in massive regurgitation to the right ventricle and atrium. When there is pulmonary atresia, rapid and severe deterioration follows ductal constriction. Survival after complete surgical repair (which is usually carried out in the third month of life) is more than 90% and about 80% of survivors have normal exercise to lerance.

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Both heroin and cocaine are on average some three times more expensive per gram for amphetamine (measured at prevailing street purities). The other side of the coin is that gross trafficking profits per given unit weight are greater for both heroin and cocaine (see Figure 76). Gross profitability for amphetamine trafficking over the 1991-1994 period has been about the same as for heroin and cocaine (see Figure 77). Germany Gross profits per kg Gross domestic trafficking profits per kg 1991 1994 avg. With retail prices for amphetamine relatively stable in Germany and wholesale prices falling (probably a reflection of less expensive but fast-growing imports from eastern Europe), gross trafficking profit margins for amphetamine are clearly rising, and so are the economic incentives for further expansion. By 1993/1994 gross profitability of trafficking in amphetamine was already higher than that of cocaine or heroin (see Figure 78). Figure 78 Changes in purities between the wholesale and the retail level have not been considered so far. The market structure in the United Kingdom differs substantially from that in the United States and only somewhat from that in Germany (compare Figure 79 with Figures 74 and 76). While in the United States retail prices of methamphetamine are at par with retail prices of cocaine, retail prices of one gram of cocaine in the United Kingdom have been about eight times higher than prices of amphetamine. Figure 79 Figure 80 In terms of trafficking profitability, Figure 80 shows that amphetamine fares significantly better than heroin or cocaine. The reason for the high gross profit margins for amphetamine are not high retail prices but rather low wholesale prices, indicating significant domestic manufacture and/or large-scale imports. While wholesale amphetamine prices in Germany, for instance, amounted to some $17,000 per kilogram over the 1991-1994 period, prices in the United Kingdom fluctuated around $3,000 per kilogram. Price differences were less pronounced at the retail level, particularly when taking the lower purities in the United Kingdom in to account. In recent years, amphetamine was traded in the United Kingdom at $15-$20 per gram, in Germany at around $35 per gram, and methamphetamine was traded in the United States at around $100 per gram. One characteristic of the amphetamine market observed in the United Kingdom and in other countries is the stable nature of unit-weight prices at street purity over time. De-fac to price changes, reflecting changes in the market structure (such as enforcement success, new manufacturers, shifting consumer preferences), are effected through changes in purity levels rather than changes in unit-weight prices. This means that stable unit-weight prices of amphetamine can go hand in hand with strongly fluctuating >pure amphetamine= prices. Even though international comparisons are partially dis to rted due to different concepts used to define the retail level, United Kingdom purity levels nevertheless appear to be on the low side. Analysis of the situation in Norway shows that gross profit margins for amphetamine as a percentage of wholesale prices are greater than for heroin or cocaine (see Figure 81 and 82). As in Germany, the gross profitability of amphetamine has been rising in Norway since 1992. Figure 81 Figure 82 As with other countries in Europe, available purity data for Norway do not distinguish explicitly between the retail and the wholesale levels and thus do not allow for any further analysis of overall gross profitability. The overall range of purities was between 30% and 70%, which is, however, sufficient to conclude that average purity of amphetamine in Norway is much higher than in the United Kingdom and similar to the United States. High purity levels are also reported from other Nordic countries and Poland (95%). Purities of amphetamine in Denmark are at around 80% at the wholesale level and around 25% at the retail level (1993). Such high purity levels in the Nordic countries could represent a more serious public health concern [Rajs and Fugelstad, 1994; Olsson et al. There is, however, some concern, for instance in the United Kingdom [Wright and Pearl, 1995], that recreational use may continue to grow and current recreational users might eventually become >hard-core= abusers. The situation in the Far East is similar to Europe and North America with regard to the higher profitability of methamphetamine trafficking than of trafficking in other drugs. Figures 83 and 84 illustrate this for Thailand, which in recent years has reported the most methamphetamine seizures in the region. Figure 83 Figure 84 Gross trafficking profit margins among countries in the Far East, differ much more than among countries in Europe or North America. Gross profit margins for methamphetamine are currently extremely high in Japan and in the Republic of Korea while in Thailand and the Philippines they are at about the same level as in Europe or North America (see Figure 85). The high gross profit margins in Japan and the Republic of Korea may, in part, be explained by Far East Gross domestic trafficking profits per kg 1991 1994 avg. Figure 85 93 successful enforcement efforts, which have substantially increased the retail prices for these substances.

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The health professional should not provide personal or medical information to the employer, unless specifcally allowed by the worker. Such communication should occur with the consent of the worker and should be limited to health issues that impact on rail safety. Where a worker is already seeing a specialist, referrals for specialist opinion or further investigation for ftness for duty may be made to that specialist. The role of medical specialists this Standard generally requires Safety Critical Workers who are assessed Fit for Duty Subject to Review to be seen by a specialist leading up to their review appointment with the Authorised Health Professional. Where appropriate and available, the use of telemedicine technologies such as videoconferencing is encouraged as a means of facilitating access to specialist opinion. Risk management approach the requirements for rail safety worker health assessments are to be determined by a risk management approach. This aims to ensure the level and frequency of health assessments conducted is commensurate with the risk associated with the tasks performed by rail safety workers. Rail transport opera to rs must establish systems and procedures to ensure rail safety workers receive the appropriate level and frequency of health assessment that corresponds with the risks associated with the tasks they perform. Figure 5 shows the ergonomics of a typical rail safety job, and provides a framework for understanding and applying a risk management approach to rail safety worker health assessments. It shows that information is gained about the rail system by the senses (mainly vision and hearing). These processes take place within the operational environment of the rail opera to r. Health assessments are one approach to treating the risk of serious incidents and the risk to individual safety, thus a mix of engineering, administrative and health assessment measures is likely to be required. When determining the health assessment requirements of rail safety workers, it is important to take in to account the operational and engineering environment, since overall risk management signifcantly determines the human attributes that are required for safety. This interaction between technology and human capabilities has implications not only for the setting and application of health standards, but also for meeting diverse legal requirements. They must be set and applied carefully to match the risks associated with the tasks to be consistent with anti-discrimination and privacy laws. As the work environment signifcantly determines the skills and attributes required and the risk involved, a risk analysis should form the basis of all rail safety worker health assessment decisions. A rail transport opera to r should perform its own risk assessments of rail safety work in its own operating environment and apply health assessments accordingly. It is not practical to individualise health assessments for every worker or task, thus a system of risk categorisation forms the basis of the health risk management system. This facilitates the risk management process and simplifes application of the health assessment requirements (refer to Section 5. Health assessments comprising screening questionnaires and clinical examinations are designed to match the risk categories and identify medical conditions that are likely to impact on safety. In turn, specifc medical criteria for various medical conditions are defned to ensure consistency of application.

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