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DAvMed 44 Haemo-endoc-gastro KCL 2011 Diabetes Mellitus Diabetes mellitus is a relatively common disorder which is of major aeromedical concern. It is regularly screened for by urine testing at routine medical examinations and in some organisations by a fasting glucose estimation. DIAGNOSIS: The finding of glycosuria should prompt a fasting blood glucose estimation. The precise diagnostic criteria for diabetes and impaired glucose tolerance are subject to small variations with time and between national advisory bodies, and the cut off points are to some extent arbitrary, given the continuous nature of the spectrum of glucose intolerance. The 2006 WHO criteria are as follows: Because of the considerable implications that the diagnosis of diabetes mellitus has for the career of professional aircrew, great care should be taken to perform a glucose tolerance test under standardised conditions. The subject should consume a diet of adequate carbohydrate content (> 250 grams/day) for 3 days prior to the test and then be fasted overnight. Blood for fasting glucose should be collected prior to the administration of 75g of glucose in 300 ml of water and a further blood sample collected 2 hours later. For subject who fit into the impaired glucose tolerance category, regular follow up is essential as they have a 5% per annum risk of becoming frankly diabetic, and carry an increased cardiovascular disease risk. An annual glucose tolerance test for such individuals is advised, but otherwise they are permitted to fly with an unrestricted category. AEROMEDICAL CONCERNS Diabetes Mellitus is a major risk factor for cardiovascular disease, and the cardiovascular mortality amongst diabetics is increased by a factor of at least 2. The all cause mortality relative risk is 1.5 - 2.0 compared to age and sex matched controls. The microvascular complications of diabetes mellitus have implications for aircrew, with retinopathy, neuropathy and nephropathy being commonly encountered. It is important to note that all these complications are equally prevalent among those the insulin dependent (type 1) and the non-insulin dependent (type 2) forms of the disease. A major aeromedical ©Prof. Anthony Batchelor 1 DAvMed 44 Haemo-endoc-gastro KCL 2011 concern in diabetes mellitus relates to the high incidence of hypoglycaemia in patients requiring pharmacological therapy. The annual incidence of significant hypoglycaemia in insulin using diabetics, defined as requiring the assistance of another person, is around 10%, and the incidence is around 30% for milder hypoglycaemic episodes. There is evidence to suggest that mild hypoglycaemia is associated with decrements of cognitive function and decision making ability at levels before clinical symptoms are apparent to the patient, and these abnormalities can persist for some time after correction of hypoglycaemia. The risk of hypoglycaemia in type 2 diabetics treated with sulphonylureas varies widely, with different series reporting rates of 2-20% per annum, but no agents of this class appear to be totally free of this potential complication. The only biguanide in use in the Western world, metformin, is not reported as causing hypoglycaemia, and this is compatible with what is understood of its mode of action. TREATMENT & AIRCREW DISPOSAL In type 2 diabetics, dietary modification, exercise and significant weight reduction may be compatible with good control, acceptable 24 hour blood glucose profiles, and even a return toward normal of the glucose tolerance test. Such an approach may allow a return to flying duties, quite possibly without limitations, but regular reviews at intervals not exceeding 6 months would be required, when objective evidence of diabetic control should be sought with HBA1c levels and capillary blood glucose profiles. At such reviews weight should be monitored and checks be made for microvascular complications and cardiovascular disease, as well as reviewing the patient for other cardiovascular risk factors (particularly hypertension). There is a strong case for performing exercise ECGs on all diabetic aviators at yearly intervals, particularly beyond the age of 40 years (required by UK CAA). The pharmacological agents permitted in the flying environment for diabetic control are limited, but the range is steadily expanding. While the intestinal alpha-1glucosidase inhibitor, acarbose, is acceptable, gastrointestinal side effects are common and it is not popular with aircrew. Metformin is permitted as pharmacological therapy for type 2 diabetics who fail to respond to diet and lifestyle changes alone, has significant cardio-protective effects in diabetics, and is not associated with hypoglycaemia. It is acceptable in professional aviators with a multi-crew restriction, but even that limitation is under review by the CAA. The thiazolidinediones, or ‘glitazones’, are primarily recommended for use in combination with another oral hypoglycaemic agent and in combination with metformin these drugs were initially not considered acceptable in the flight environment because of concerns over the possible risk of hypoglycaemia. However, with increasing experience and confidence, this combination is now permitted for restricted flying duties, in a multi-crew environment. Glitazones may also be considered for use as sole therapy in patients who suffer unacceptable side effects with metformin (see table). The risk of hypoglycaemia is considered unacceptable with all the currently available sulphonylurea drugs and none of the other classes of emerging agents is as yet considered acceptable in aircrew. However, the development of the incretinbased agents has been an exciting therapeutic progression and the use of DDP-4 inhibitors (the ‘glyptins’) in the flying environment are under active review. Flying categories for type 2 diabetics requiring drug therapy would usually exclude high performance aircraft, and involve restriction to multi-crew aircraft types. A further concern in military flying is the effect of military operations on diabetic control with irregular working hours, lack of access to normal dietary sources, and extreme emotional and physical stress all tending to disturb the normal equilibrium. Insulin dependent diabetes is widely considered a complete bar to all types of flying, the risk of hypoglycaemia being considered incompatible with flight deck duties. No level of HBA1c in type 1 diabetics treated with insulin has been shown to be associated both with adequate diabetic control (particularly important now that the risk of complications has been clearly demonstrated to be related to blood glucose levels) and freedom from significant risks of hypoglycaemia. This point of view has been contested in the USA and Canada, where several hundred private pilots have now been licensed to fly with onerous safeguards in place to (hopefully) preserve flight safety. These pilots have had to demonstrate good diabetic control and absence of complications, together with freedom from hypoglycaemic episodes for at least one year. ©Prof. Anthony Batchelor 2 DAvMed 44 Diet alone; glitazones Fit all classes Haemo-endoc-gastro KCL 2011 Diagnosis of Diabetes Mellitus Temporarily Unfit Insulin – permanently unfit acarbose; Metformin +/- glitazone Suphonylureas Class 1 (OML) / Class 2 Unfit Class 1 / Class 2 (OSL) unrestricted AIRCREW SELECTION A history of any form of diabetes is unacceptable for aircrew selection, and in the Royal Air Force a strong family history (2 first degree relatives with diabetes) would be regarded as an indication for considering a glucose tolerance test prior to selection. ©Prof. Anthony Batchelor 3 DAvMed 44 Haemo-endoc-gastro KCL 2011 Thyroid Disease Thyroid diseases are the second most commonly encountered endocrine disorders and are important to identify as abnormalities of thyroid function can have significant effects on judgement, psychomotor functions, mood, reaction times and many other facets of human physiology and psychology. What is more, they are usually eminently treatable, with a subsequent return to full aircrew duties being possible. THYROID FUNCTION TESTS Normal control over thyroid function is dependent upon a negative feedback control system, which starts with synthesis of thyrotrophin releasing hormone by the hypothalamus. This acts within the anterior pituitary to liberate thyroid stimulating hormone (TSH) which in turn influences the thyroid gland to increase its output of thyroxine (T4) and tri-iodothyronine (T3). These hormones circulate in plasma bound to protein, with only small amounts of free T4 and even smaller amounts of free T3 being present. Within peripheral tissues a proportion of T4 is converted to T3 which is the most active thyroid hormone. Plasma T4 and T3 exert a negative feedback influence on the anterior pituitary release of TSH, via the hypothalamus. Radioimmuno assays of TSH, free T4 and free T3 nowadays provide a reliable and accurate biochemical assessment of thyroid function in most circumstances. The TSH level is the most reliable single test, is both sensitive and specific, being depressed in situations of excessive thyroid activity, and elevated in hypothyroidism. However it needs to be appreciated that TSH levels can be altered in acute and chronic disease states when misleading results can be obtained. Free T4 is an accurate and useful second line measurement of thyroid function, but can also be influenced by drugs and disease. HYPERTHYROIDISM This is a syndrome resulting from excess circulating T4 and/or T3. The most common cause is Graves’s disease, with other causes including toxic multinodular goitre, solitary toxic nodule, and acute thyroiditis. The hyperthyroid syndrome is characterised by weight loss with a good appetite, fatigue, muscular weakness and insomnia, sweating and heat intolerance, palpitations, tachycardia and is occasionally complicated by atrial fibrillation. The patients often exhibit agitation and tremor, with emotional lability, and diarrhoea is common, as is oligomenorrhoea in females. Graves’ disease is commoner in females in a ratio of 5:1, and is an immunologically mediated disorder in which IgG antibodies (thyroid stimulating antibodies) bind to TSH receptors within the thyroid, while other related antibodies act on retro-orbital tissues. Such patients exhibit hyperthyroidism, usually with a diffuse goitre, often with a bruit over the gland. 50% will show an ophthalamopathy with proptosis and impairment of extra-ocular muscle function. The disease is a remitting and relapsing disorder whose acute symptoms can be eased by beta blockers, but the definitive therapeutic modalities include antithyroid drugs, subtotal or total surgical thyroidectomy, or radio-active iodine therapy. The aeromedical concerns of the hyperthyroid state are multiple and self evident from the above list of possible symptoms, but may also include fatigue, poor concentration and impaired judgement. Drug treatment consists of using antithyroid compounds, carbimazole and propylthiouracil being the most frequently prescribed in this country, for a period of 18 months to 2 years. These drugs not only block the synthesis of thyroxine within the thyroid gland, but also appear to exert an immunological effect resulting in falling titres of thyroid stimulating antibodies. Traditionally the drug dose is titrated against thyroid function, but an increasingly favoured approach is to maintain full doses of the thyroid blocking compound, avoiding hypothyroidism by the addition of oral L-thyroxine supplements as ©Prof. Anthony Batchelor 4 DAvMed 44 Haemo-endoc-gastro KCL 2011 required. Relapse rates after medical treatment are high, around 60-70% but may be lower with the second of these approaches, where a greater suppression of antibody levels appears to be achieved. Relapse would be an indication to consider radio-iodine therapy, as would drug side effects such as skin rashes or evidence of bone marrow aplasia. Radioactive iodine therapy has much to commend it from both the general clinical and aviation medicine view points. After initial control of the acute hyperthyroid estate with anti-thyroid drugs, iodine 131 treatment usually results in a permanent remission of the disease, but with a very significant chance of the subsequent development of hypothyroidism. The treatment is simple and quick, and appears to be remarkably safe. Although initially this approach was only offered to more mature adults (over 40 years) many centres are now offering radioactive iodine therapy to much younger individuals. Those treated with this modality require regular long term follow up of their thyroid function, with replacement Lthyroxine being provided when, and if, they develop hypothyroidism, as indicated by a rising TSH level. Subtotal or total thyroidectomy is less frequently used these days, except for young people who have relapsed after medical treatment, and do not wish radioactive iodine treatment. Complications include hypoparathyroidism (usually only temporary) and recurrent laryngeal nerve damage. HYPOTHYROIDISM This is a syndrome resulting from reduced circulating levels of T4 and T3, and is most commonly caused by autoimmune thyroiditis or Hashimoto’s disease. It can also be iatrogenic, induced by surgery or iodine 131 treatment, and more rarely may be related to iodine deficiency, other drug treatment, or dyshormonogenisis. The disorder is characterised by fatigue, weight gain and cold intolerance, with patients complaining of dry skin, hair loss, constipation and muscular stiffness. It is complicated by hyperlipidaemia, the rapid evolution of ischaemic heart disease, depression, vocal changes, and carpal tunnel syndrome. Clinical signs include the characteristic skin and facial changes, bradycardia and a delay in the relaxation phase of tendon jerks. In Hashimoto’s disease there is usually a firm diffuse goitre without a bruit, and there is an association with other autoimmune disorders. Thyroid antibody titres are substantially elevated. Treatment consists of replacement L-thyroxine, increasing the dose slowly until clinical and biochemical evidence of a return to the euthyroid state is achieved. In the long term a regular monitoring with clinical assessment and TSH levels is required, as drug compliance is a significant problem in a minority. AEROMEDICAL DISPOSAL Abnormalities of thyroid function should initially result in subjects being made unfit for all aircrew duties. Hyperthyroid subjects can be considered for limited flying duties (multicrew) once they are euthyroid on treatment, but usually not before 4 – 6 months, and will require close monitoring. After one year those with stable thyroid function can be considered for unrestricted flying duties, but with indefinite medical follow up. Those subjects with treated hypothyroidism can be considered for a return to full flying duties once a euthyroid state is established on replacement therapy, provided all symptoms and complications of the disorder are resolved. ©Prof. Anthony Batchelor 5 DAvMed 44 Haemo-endoc-gastro KCL 2011 ANAEMIA AEROMEDICAL CONCERNS Decreased oxygen carrying capacity of the blood leads to an increased cardiac output for a given work load. In turn, there is a decreased effort tolerance and sub-clinical cardiovascular problems may be unmasked. The presence of anaemia may also be an indicator of a wide variety of underlying disease processes. CLASSIFICATION Nutritional - iron - vitamin B12 - folic acid Haemolytic - inherited - acquired - red cell membrane defects - abnormal haemoglobin - red cell enzyme abnormalities - immune - non-immune Bone marrow - aplastic - suppressed by chronic disease - infiltration SPECIFIC EXAMPLES Iron deficiency - in males consider GI blood loss, diet and malabsorption. Worldwide, intestinal parasites are the commonest cause. - in females, consider menstrual losses in addition Runners’ anaemia - commonly a physiological adaptation associated with increased red cell mass and even greater increase in plasma volume - ? traumatic haemolysis or traumatic blood loss - probably not significant Beta-thalassaemia trait - such individuals usually have only a modest stable anaemia, and a normal exercise tolerance. They may be fit for aircrew selection but each case will have to be decided on the basis of individual assessment. Congenital spherocytosis - when treated with splenectomy in childhood, may maintain near normal haemoglobin levels. However, the susceptibility of splenectomised subjects to certain infections and particularly to malaria, may have significant implications for military aircrew selection. Sickle cell trait ©Prof. Anthony Batchelor - contentious issue. Risk of precipitating sickling has been considered to be associated with fever, dehydration, immobility and reduced ambient inspired oxygen tension. In practice, flying duties do not seem to present a significant risk to fit young individuals, and most organisations (including RAF) have stopped screening. 6 DAvMed 44 Haemo-endoc-gastro KCL 2011 ANAEMIA AND AEROMEDICAL DISPOSAL Aircrew selection - bar to flying training - possible reconsideration after investigation Trained aircrew - symptomatic or significant anaemia (Hb < 12 g/dl) - immediate grounding; return to flying depends upon finding a curable cause - mild anaemia - depends on cause and individual assessment Aeromedical evacuation ©Prof. Anthony Batchelor - acute anaemia; Hb > 9-10g/dl (but dependent on cause and other conditions) - chronic anaemia; Hb ? > 7 g/dl 7 DAvMed 44 Haemo-endoc-gastro KCL 2011 Air Travel and Venous Thrombosis Venous thrombo-embolism (VTE) • • • • Incidence 1 in 1,000/annum in developed counties Increases with age (1 in 100,000 in childhood to 1% in old age) Virchow’ triad – – Stasis of blood – Changes in blood – Changes in vessel wall Genetic and acquired Travellers’ Thrombosis • • • • • • • • • • • Simpson 1940: increased incidence of DVT (deckchair thrombosis) 1954 Homans: venous thrombosis and prolonged sitting (2 car; 2 flying; 1in a theatre) 1977 Symington & Stack “economy class syndrome” 1984 Cruickshank et al “economy class syndrome” 1996 Eschwege & Robert: increased incidence of DVT in commuters caught up in Paris bus strike 1998 Mercer & Brown: 134 cases of PE - 50% had travelled for > 4 hours in previous 31 days 1999 Ferrari et al: 160 cases of VTE - 39 had recently travelled (9 flying; 28 car; 2 train) Kesteven & Robinson: 86 pts who developed VTE within 28 days of flying • 72% had at least one risk factor prior to flight • 87% occurred after return trips or after very long trips • only 2% has no risk factors and no history of a return journey • 92% developed symptoms within 96 hours of flight Kraaijenhagen - 788 pts with VTE; unable to demonstrate association with air travel versus controls ten Wolde et al - 198 pts; no association with travel of > 3-4 hrs Dimberg World Bank study - no increase in VTE among frequent travellers compared to nontravelling controls VTE and Coagulation Abnormalities • Thrombophilia – Deficiencies of proteins C & S, antithrombin (rare – increase risk ten fold) – Factor V Leiden • present in 5% of the white population • present in 20% of those with VTE – Prothrombin 20210A present in 2% population; 6% with VTE – Factor VIII levels > 150% of normal in 11%; but 25% with VTE – Homocysteine > 18.5 micro mol/l in 5%; but 10% in those with VTE: risk x 2.5 ( > 20 micromol/l risk x 3-4) VTE and Risk Interaction • • Gene – gene interaction Gene – environment interaction – Baseline female VTE risk 0.8 per 10,000/year – Risk for females on OCP = 3.0 per 10,000/year (relative risk 3.7) – Risk females + factor V Leiden = 5.7 per 10,000/year (relative risk 6.9) – Risk females + factor V Leiden + OCP = 28.5 per 10,000/year (relative risk 34.7) ©Prof. Anthony Batchelor 8 DAvMed 44 Haemo-endoc-gastro KCL 2011 Risks Peculiar to Flying? • • • • • • • • hypoxia ) - but no experimental evidence (see RAF CAM/ Leicester University study!) hypobaria ) and consider professional aircrew (no XS risk) and populations living at altitude dehydration – mucosal dryness, but no significant overall fluid loss alcohol – leading to diuresis, somnolence and immobility? air quality – contentious, but no evidence for adverse influences after major studies fluid retention immobility posture Patrick Kesteven - 2001 • • • • • Fixed population of 650,000 (Newcastle) all cases of VTE presenting to hospital 1,250 over a two year period only 47 (3.8%) had made a journey of > 100 miles in the previous 4 weeks – 60% by air; 36% by road; 4% by rail – at least one medical risk factor was present in all but three of the 47 VTE incidence in NE England: 1 in 27,660 per annum VTE – models of risk: • Cumulative risk – baseline risk – variable (age) – fixed (coagulation abnormality) – added factor (eg OCP) – intercurrent event (eg. trauma, immobility etc) Rosendaal Lancet 1999;353:1167 ©Prof. Anthony Batchelor 9 DAvMed 44 Haemo-endoc-gastro KCL 2011 VTE and Flying Risk Strategy • Mildly increased risk – age > 40 years – obesity – minor surgery within 3 days – active inflammatory disease • Moderately increased risk (Advice as above; consult GP; – heart failure consider graduated support stockings; not aspirin!) – recent MI (within 6/52) – oestrogen therapy – pregnancy/postnatal – lower limb trauma (within 6/52) – polycythaemia – paraplegia • High level risk (Advice as above; consult GP; – previous VTE graduated compression stockings; – known thrombophilia consider low molecular weight heparin) – recent major surgery (within 6/52) – previous CVA – malignancy – family history of VTE ©Prof. Anthony Batchelor (General advice – hydration, mobility; consider support socks/stockings) 10 DAvMed 44 Haemo-endoc-gastro KCL 2011 GASTROINTESTINAL DISEASE (NB – the notes from this point on have not all been completely revised since 2004/5. They are included for interest, but should be read in conjunction with Ed 4 of Ernsting and hand outs from relevant lecturers) Gastrointestinal disorders are common within the age group represented by flying personnel, and acute gastroenteritis has repeatedly been reported as being the commonest cause of sudden in flight incapacitation of aircrew. TRAVELLERS’ DIARRHOEA In excess of 1000 million people undertake international travel each year and of those over 10% travel from industrialised to developing countries. Of the latter group acute episodes of diarrhoea are exceedingly common, with reported rates varying from 20-50%. Most of these attacks are self limiting and harmless but nevertheless they can interfere with holiday plans, can disrupt a business trip, and they can have significant economic implications to host nations. Equally such attacks can have very significant implications for military operations and for the crew of civil airline operations. Aetiology It is now well established that the aetiology of travellers’ diarrhoea is infective, with pathogens being demonstrated in well over 80% of subjects. The pattern of these pathogens is closely related to the pattern that is endemic in the host country, and is the same spectrum of enteropathogens that cause infantile diarrhoea in these countries. Like the infants, the visitors have low resistance and high susceptibility. By far the commonest pathogen implicated on a world wide basis is enterotoxigenic E coli, accounting for some 40% of cases, but Shigella, Campylobacter and Salmonella are frequently represented, together with Protozoa such as Giardia lamblia, Cryptosporidium parvum, and Entamoeba histolytica. Further protozoan infective agents are discovered at regular intervals, and about 10% of cases are due to viruses, the rota virus and the norwalk viruses being most commonly implicated. Transmission Transmission is via contaminated food and water. It must be remembered that ice is only frozen water and can be an unsuspected source of infection, and that chlorination of swimming pool water may not be effective in eliminating protozoal cysts. Clinical Features The attacks of diarrhoea start most commonly on the third day and usually resolve spontaneously within 2-4 days. More protracted symptoms, lasting for longer than one month, occur in only 1-2% of the population involved. In most cases the illness is mild, with bowel actions not exceeding 6 per day, but abdominal cramps together with nausea and vomiting lead to significant short term morbidity and disability. Up to 20% of sufferers will have fever or bloody diarrhoea suggestive of enteroinvasive disease. ©Prof. Anthony Batchelor 11 DAvMed 44 Haemo-endoc-gastro KCL 2011 Prevention In planning a strategy for prevention of traveller’s diarrhoea it is important to assess the risks to the health of the individual, the effects of possible incapacitation to the mission on which the individual is involved, and the risks within the country of destination. Individuals at high risk of infection or from severe consequences of such infection, include those aged less than 6 years, those with reduced gastric acidity (gastric surgery, acid suppressing drugs) and those with immuno-deficiency disorders. Subjects with chronic inflammatory bowel disease may also be at increased risk of relapse. Prevention is firstly based upon avoiding the enteropathogen. Travellers are advised to avoid uncooked or unpeeled food, ice cubes and tap water, and should be aware of the risks of ingesting water in swimming pools, lakes, and even sea water near sewage effluent points. Hot food should be served at a temperature greater than 65% centigrade and flight crews should be advised to choose different items from restaurant menus. For subjects at high personal risk, or for those deemed to be on missions of critical importance to military operations, political or business matters etc, in whom sudden illness could have far reaching consequences, antimicrobial chemoprophylaxis should be considered. There is no doubt that this approach is highly effective, with the 4-fluoroquinolone drugs being the most effective. The possibility of encouraging drug resistant strains remains a controversial discussion point. Non-antibiotic prophylaxis with bismuth subsalicylate is moderately effective, but the consumption of live yoghurt (infected with lactobacillus) has not been shown to have any significant effect. Treatment The treatment is the therapy of acute gastroenteritis, with replacement of fluid and electrolyte loss being fundamental. Glucose/electrolyte solutions are ideal if available, but if not a high oral fluid intake using salty soups and fruit juices can be most effective, and can be supplemented by complex carbohydrate sources such as rice, bread and potatoes. Antimotility agents such as loperamide provide useful symptom relief, but should be avoided in those with evidence of dysentery. The use of antibiotics is controversial though effective, but is indicated for specific infections such as shigella, typhoid and amoebiasis. One study of military personnel on jungle training exercises has shown a single dose of ciprofloxacin 500 mgs to be exceedingly effective in reducing the duration of diarrhoea, the number of fluid stools passed, and in promoting an early return to fighting fitness. Aircrew should not fly for between 24 and 48 hours after symptoms have resolved, depending on operational need, thus allowing time for restoration of fluid and electrolyte equilibrium. PEPTIC ULCER DISEASE Peptic ulcer disease remains common in the United Kingdom with 4,111 deaths in the United Kingdom in 1996 having been certified as due to this cause. At that time it was the tenth commonest cause of death, slightly commoner than road traffic accidents, and the death rate from peptic ulcer has risen over the past 20 years. Much of this mortality, however, does occur in an increasingly elderly population, but peptic ulcer disease results in 40,000 hospital admissions per year and is estimated to cost the NHS £50 million. Duodenal Ulcer Epidemiology ©Prof. Anthony Batchelor 12 DAvMed 44 Haemo-endoc-gastro KCL 2011 This disorder has a remitting/relapsing natural history and is commonest in young males. The incidence is falling in men, but stable in women and duodenal ulcer is substantially commoner than gastric ulcer in males under 40 years. A genetic component to the aetiology is indicated by the increased history amongst first degree relatives and the increased incidence in blood group ‘O’ individuals, and nonsecretors of blood group antigens. Non-steroidal anti-inflammatory drugs account for a small percentage of DU’s, and are associated with complications of duodenal ulcers. Over 96% of duodenal ulcer disease is now known to be associated with a Helicobacter pylori gastritis. This infection appears to be an essential component of the cocktail of factors required before duodenal ulceration can occur, and eradication of the organism is associated with a dramatic reduction in relapse rate. Clinical Features The symptoms of localised epigastric pain eased by food, or alkalis, often waking the patient at night, and occurring in a cyclical pattern of remissions and relapses, is well known. However it is important to appreciate that atypical symptom patterns are common. The diagnosis is most satisfactorily made by endoscopy particularly in those with distorted duodenal caps from previous ulcer disease, and the procedure permits biopsy for Helicobacter pylori infection to be carried out at the same time. Management The management of duodenal ulcer disease was revolutionised in the late 1970’s with the introduction of H2 receptor antangonists. For the first time drugs were available which produced acid suppression which was adequate to allow prompt symptom relief, and high ulcer healing rates. However, it rapidly became apparent that intervention with such agents did not change the natural history of the disease, and cessation of therapy was associated with a very high relapse rate of 60-80% per year. The concept of maintenance therapy with low dose H2 receptor antangonists was then introduced and this proved to be an effective strategy, lowering the relapse rate to 20-30% per annum. Throughout the 1980’s gastric surgery became steadily less popular as an approach to the management of chronic relapsing duodenal ulcer disease, even though fairly sophisticated techniques such as highly selective vagotomy had evolved in an attempt to reduce gastric acid output with minimal side effects. Most series continued to show, however, that surgery was associated with a 15-40% relapse rate, symptomatic and metabolic complications were common, and concerns have been expressed about the long term cancer risks. The safety and efficacy of medical maintenance treatment was a major factor in the rejection of gastric surgery, and the advent of proton pump inhibitors in the late 1980’s, with their much more powerful suppressive effect on gastric acid production, provided a means of healing most resistant ulcers. During this period, aircrew with duodenal ulcer disease were routinely treated with H2 receptor antangonists, subjected to endoscopic follow up and grounded for a lengthy period before being permitted to return to flying duties. Relapsing ulcer disease was usually associated with maintenance therapy and a restricted aircrew category. Although the medical profession appeared slow to realise the significance of the discovery of spiral organisms in the gastric mucosa of human beings with gastritis and ulcer disease, it is now widely accepted that helicobacter pylori is an essential component in the aetiology of duodenal ulcer disease, and is implicated in a high proportion of gastric ulcers. Eradication of the organism has been associated with dramatic reductions in ulcer relapse rate in large numbers of series in the short term and evidence for long term remission is also emerging. This has led to a radical re-think of the management of ulcer disease in aircrew, with much shorter periods of grounding for uncomplicated ulcer disease, and restoration of unrestricted flying category in those in whom ulcer healing and H pylori eradication is confirmed. A more cautious approach is taken with complicated ulcer disease. ©Prof. Anthony Batchelor 13 DAvMed 44 Haemo-endoc-gastro KCL 2011 Duodenal ulcer Management Strategy in Military Aircrew Uncomplicated DU - treat with ulcer healing agent and Helicobacter pylori eradication - unfit all flying duties for 2/12 - endoscopy at 2/12, check ulcer healing and biopsy for H pylori - or substitute breath test/faecal antigen test to confirm H pylori clearance? - if clear, upgrade full flying duties DU plus haemorrhage - same treatment - unfit full flying duties for 6/12 - check endoscopy and H pylori status - if clear, return to full flying duties Perforated DU - downgraded 1 year - H pylori eradication Rx if relevant - check endoscopy at 1 year - if clear, return to unrestricted flying duties NSAID associated DU - H pylori +ve: same as simple DU - H pylori -ve: conventional Rx, check ulcer healing at 8/52, if clear - full flying duties and no further NSAIDs INFLAMMATORY BOWEL DISEASE Ulcerative colitis and Crohn’s disease are the two most common forms in inflammatory bowel disease and are chronic remitting/relapsing disorders requiring long term medical treatment and follow up. They are prone to a spectrum of complications and their diagnosis has significant implications for the careers of aviators. Ulcerative Colitis Ulcerative colitis is a chronic inflammatory disease of the large bowel, with a relapsing/remitting natural history, and of unknown aetiology. The inflammatory process is normally confined to the mucosa, starting in the rectum and spreading proximally to involve variably amounts of the colon. The aetiology is not understood, but probably represents an interaction between genetic predisposing factors, exogenous and endogenous triggers, producing an inflammatory process which is mediated by the immune system. Epidemiology The disorder has a similar incidence throughout all ages after puberty, at around 5-8/100,000 in North Western Europe and in people of Anglo-Saxon origin. It is notably less common in smokers. Prognosis ©Prof. Anthony Batchelor 14 DAvMed 44 Haemo-endoc-gastro KCL 2011 From the aeromedical view point it is more relevant to concentrate on the prognosis than to enter lengthy discussion on the clinical features of the disorder which can be distilled from any standard text. Ulcerative colitis is associated with only a slight excess mortality in the year of diagnosis and this is almost entirely confined to pancolitis occurring in the elderly. There is no overall excess mortality. The disorder is, however, a relapsing one and over 95% of patients can be expected to have relapsed by 10 years from the time of the presenting episode. Relapse rates appear to be directly related to the extent of the colon involved, and are higher in the young. The most important observation, however, is that relapses are totally unpredictable, which naturally has implications for aviators and also for military personnel. One mode of therapy is surgical resection of the colon and 10-25% of subjects can expect to have colonic resection by 10 years from presentation, depending upon their geographical location. Surgical intervention tends to be offered at an earlier stage in Scandinavian countries than in the UK, and some surveys have indicated that the social and employment consequences of the disorder are less marked in these countries as well. The introduction of ileal pouch surgery has made colonic resection appear rather more acceptable to patients, particularly to the young, but is not without its complications. Not only is there a significant chance of relapse of disease activity, with over 30% of sufferers having a relapse in any one year (45% in the 20-40 year age group), but there is also a significant risk of disease extension with each relapse. In the longer term there is a well documented cancer risk associated with ulcerative colitis, related to the extent of bowel involvement, the subjects age at presentation, and the duration of disease. Cardiovascular mortality amongst sufferers, however, is reduced, and this is almost certainly related to the lower cigarette smoking rate amongst subjects. Management The treatment of acute episodes will not be discussed, beyond saying that systemic and topical steroids are the mainstay of therapy. Maintenance treatment, however, is a vital component of management and it has been repeatedly shown that 5 aminosalicylic acid (5-ASA) delivered directly to the colon has a significant positive impact on relapse rates, reducing the overall annual rate to around 10-15%. This remains true even after lengthy periods of remission on treatment, so that discontinuing the drug is associated with an immediate increase in annual relapse. The first 5 ASA drug was sulphasalazine in which 5 ASA was bonded onto a sulphonomide antibiotic, thus avoiding absorption in the small intestine, but the active agent being liberated by bacterial cleavage of the bond in the colon. A relatively high incidence of side effects from this drug is related in large part to the sulphapyridine component and a number of agents have now appeared on the market which use alternative approaches to targeted delivery of 5-ASA in the colon. These have all been shown to be effective in reducing relapse rates, tend to have a lower incidence of side effects, but their differing delivery patterns need to be considered when targeting specific regions of the terminal ileum and colon. The one remaining concern is of nephrotoxicity from 5-ASA which is exceedingly uncommon, but well recognised. Factors Affecting Relapse Rates Upper respiratory tract infections and analgesic ingestion have both been shown to have a significant association with relapse of ulcerative colitis, but it is possible that they may represent the same phenomenon, i.e. paracetamol/aspirin consumption for URTIs. Although it has been difficult to prove a statistical association, many clinicians are convinced that gastroenteritis, dietary indiscretion, foreign travel, and particularly physical and psychological stress, are also strongly related to relapse. A number of these factors have significant implications for aircrew on world-wide operations, and military aircrew in particular. ©Prof. Anthony Batchelor 15 DAvMed 44 Haemo-endoc-gastro KCL 2011 Aeromedical Concerns Sudden incapacitation is an unlikely event to be associated with ulcerative colitis when the disorder is in remission. However, the disease has an unpredictable relapse pattern, and the need for medical surveillance and for maintenance therapy, can be expected to have an impact on operational availability of sufferers. Reduced operational efficiency may also be a factor worthy of consideration with many nonspecific symptoms having been clearly associated with ulcerative colitis, even in remission, and these include a reduced sense of well being, fatigueability, and a variety of drug side effects. Irritable bowel symptoms are also extremely common, even during remission, and the sense of rectal “unease” which afflicts so many sufferers is undoubtedly a major distracting influence. For those aircrew with limited disease in remission, return to restricted flying under regular supervision may be possible. For extensive or complicated colitis, the outlook for a flying career is usually poor. Crohn's Disease Crohn’s disease is an inflammatory disease affecting the whole of the GI tract, usually distributed in a patchy fashion and involving the large bowel only in 30%, the small intestine alone in 40% and both large and small intestines in 30%. The distal ileum is the commonest single site likely to be involved. Histologically it is characterised by the presence of non-caseating granulomata, and involvement of the full thickness of the bowel wall, in contrast to the predominantly mucosal disease of ulcerative colitis. The aetiology is unknown, but unlike ulcerative colitis it is commoner in smokers and many patients appear to have had diets containing an unduly high proportion of refined sugars early in life. It most commonly begins in early adult life, follows a remitting relapsing pattern, and is frequently complicated by abscess and fistula formation, haemorrhage, peri-anal disease, and obstructive symptoms. Prognosis The recurrence rate of Crohn’s disease is almost 100% at 10 years, and 30% of sufferers can expect to have surgery performed in the first year, with a surgical intervention rate of 5% per year in the remainder. In addition to local complications, nutritional deficiencies and anaemia are common, and remote complications such as iritis and arthritis are not rare. Aeromedical Disposition Small bowel Crohn’s disease can rarely be expected to be compatible with a return to full flying duties because of the unexpected relapses, complications and symptoms described above. Occasional individuals in full remission, with no complications and maintained on low dose immunosuppressant therapy (eg prednisolone, azathioprine) may be considered for restricted flying duties under close supervision. If confined to the large bowel alone, limited and uncomplicated disease in complete remission for one year, with resolution of endoscopic changes and no markers of disease activity, might be compatible with a limited flying category for military aircrew, subject to six monthly reviews. Generally the prognosis for a full flying career in this disease is exceedingly poor. ©Prof. Anthony Batchelor 16