On 2 August 1990, Iraq invaded Kuwait. Four days later, nearly US troops and an

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1 754 * A REVIEW OF THE EVIDENCE FOR A GULF WAR SYNDROME Khalida Ismail On 2 August 1990, Iraq invaded Kuwait. Four days later, nearly US troops and an international oalition of military personnel were mobilised to the Gulf under Operation Desert Shield, whih inluded members of the UK Armed Fores under Operation Granby. The air ampaign, Operation Desert Storm, began on the 17 January On 24 February 1991, a ground war was onduted whih lasted only four days. Thousands of Iraqi soldiers were killed in the hostilities, on the infamous Basra Death Road, one of the main routes they used to enter and leave Kuwait. There were less than 300 deaths in the allied fores. Within months after the hostilities had ended reports of US Gulf veterans omplaining of various symptoms began emerging. Veterans groups, the media, and ertain researhers alleged that some Gulf veterans were suvering from a Gulf War syndrome, a new disorder, whih they believed was aused by various environmental exposures while in the Gulf theatre. This artile addresses the ase for a Gulf War syndrome. The proess by whih a new illness arises depends first on establishing whether its linial features are suyiently diverent from other known onditions and then whether aetiologial fator(s) an be identified. 1 Soial and ultural fators, suh as the pereption of one s health and auses of disease, are also relevant in the emergene of a new disorder. Outome, interventions, and lessons for the future are important. The literature on eah of these topis will be reviewed. CLINICAL Correspondene to: Dr Khalida Ismail, Department of Psyhologial Mediine, Guy s, King s and St Thomas Shool of Mediine, 103 Denmark Hill, London SE24 0AQ, UK khalida.ismail@iop.kl.a.uk FEATURES OF ILL HEALTH IN GULF VETERANS Epidemiologial studies Initial ase reports desribed non-speifi symptoms suh as fatigue, headahes, and rashes that did not fall into reognised diagnosti ategories. In the USA, Gulf veterans were invited to join voluntary medial registries run by the US Department of Defense for those still serving (the Comprehensive Clinial Evaluation Program) 2 and the Department of Veteran AVairs for disharged personnel. A few individuals did have reognised diseases, suh as leishmaniasis, but the majority presented with non-speifi symptoms. Fatigue, headahe, memory problems, sleep disturbanes, skin rashes, joint pains, and dyspnoea were the most ommonly reported symptoms in both registries. Three International Classifiation of Diseases, ninth revision (ICD-9) ategories, musuloskeletal disorders (18.6%), mental disorders (18.3%), and symptoms, signs and ill defined onditions (17.8%), aounted for over 50% of diagnoses of the first veterans who partiipated in the Comprehensive Clinial Evaluation Program. 2 The UK Ministry of Defene voluntary register, the Medial Assessment Program, found no evidene of a new syndrome nor a dramati over representation of any one disorder. 3 As voluntary registers may have been over represented by people who pereive themselves to be ill, studies representative of the military population were needed. Population based studies have found that Gulf veterans onsistently self report a wide range of non-speifi symptoms and onditions ompared to military ontrols. A telephone survey of a random sample of Gulf veterans who resided in Iowa when they enlisted had higher rates of self reported medial and psyhiatri symptoms, suh as asthma, depression, post-traumati stress disorder, fatigue, fibromyalgia, and alohol abuse, than ontemporary military personnel who were not deployed to the Gulf. 4 A survey of nearly 4000 urrently ative personnel in four US Air Fore units found that Gulf veterans reported an exess of all 35 symptoms enquired ompared to non-gulf veterans; the most ommon were sinus ongestion, headahe, fatigue, joint pain and stivness, ognitive diyulties, and diyulty sleeping. 5 In a survey of 1500 ative duty US Navy mobile onstrution battalion personnel (Seabees), Gulf veterans reported a higher prevalene of symptoms, mainly fatigue, forgetfulness, sleeping diyulties, rash, joint pains and headahes, psyhologial symptoms onsistent with post-traumati stress disorder, and depression. However, objetive assessment did not reveal any diverenes between hand grip strength, serum ferritin, C-reative protein, haptoglobin or lung funtion. 6 In a survey of military personnel in the UK, Gulf veterans reported all 50 symptoms enquired two to three times more frequently than two

2 Eduation Prevalene of symptoms Gulf Bosnia Era Box 2: Clinial features of Gulf War syndrome Gulf veterans are reporting symptoms two to three times more frequently than military personnel who were not deployed to the Gulf The symptoms are multisystem and non-speifi, suh as fatigue, headahe, subjetive memory problems, sleep disturbane, and musuloskeletal pains The underlying pattern of symptom reporting is not unique to Gulf veterans There is some evidene that symptoms are assoiated with psyhologial onditions Despite the inreased symptom reporting, the overall physial funtioning of Gulf veterans is not greatly impaired *755 0 Most frequent Least frequent Figure 1 Distribution of 50 symptoms in three UK military ohorts: deployed to the Gulf, deployed to Bosnia, and Era (serving in the military during the Gulf onflit but not deployed to the Gulf). military ontrols, veterans who were on another deployment (Bosnia peae keeping), and veterans who were in ative servie at the time but not deployed to the Gulf 7 (fig 1). The most ommon symptoms in all three ohorts were sleep diyulties, irritability, headahes, fatigue, forgetfulness, and joint pains (box 1). Symptom prevalene in the ontrol groups was similar to eah other suggesting that there was a Gulf speifi rather than deployment evet. While the pereption of general health was signifiantly lower in the Gulf group than the other two groups, the level of physial funtioning was about the same in all three groups. Box 1: The 15 most frequent symptoms (%) by deployment (men) Symptoms Gulf (n=3284) Bosnia (n=1815) Era (n=2408) Feeling unrefreshed after sleep Irritability/outbursts of anger Headahes Fatigue Sleeping diyulties Forgetfulness Joint stivness Loss of onentration Flatulene/burping Pain without swelling/redness Feeling distant/ut ov from other Avoiding doing things/situations Chest pain Feeling jumpy/easily startled Sore throat There was no onsistent exess of admissions to military hospitals for explained and unexplained onditions among ative duty Gulf veterans. 8 An eight year retrospetive study of all UK Gulf veterans reported a slightly inreased mortality rate from external auses, mainly aidents, ompared to mathed non-gulf military personnel while mortality rates from disease related auses were lower. 9 These results are similar to earlier US findings involving over veterans. 3 Statistial approahes to Gulf war related ill health Fator analysis is a set of statistial methods that examine the latent fator struture that underlies the orrelations between the set of symptoms observed. It has been used as a parsimonious method of representing and validating multisymptom data on Gulf War veterans. 5 One unit in Texas suggested that there was a Gulf War syndrome based solely on the fator struture in a non-representative sample of US Gulf veterans This led to muh ontroversy in the sientifi ommunity and Gulf veterans partiularly after further fator analysis studies were unable to orroborate the findings. 10 In a fator analysis using 50 symptoms in a UK sample of Gulf veterans, the first three fators were haraterised by symptoms of mood ognition, suh as headahes, irritability, sleep diyulties, and distressing dreams; respiratory system symptoms, suh as shortness of breath and wheezing; and peripheral nervous system symptoms, suh as tingling and numbness. There were no great diverenes in the three fator strutures in Gulf veterans ompared to Bosnia veterans and non-deployed veterans. 10 In a US sample of ative duty Navy personnel, five fators were identified whih were similar in both Gulf and non-gulf veterans, although Gulf veterans had higher fator sores refleting greater severity of symptoms. Another US study derived a three fator struture with similar symptoms loading onto them in both Gulf and non-gulf samples. They labelled these fators as somati distress, psyhologial distress, and pani. The fators were highly onvergent with eah other in eah of the two samples. 3 Relation between symptoms and mental health All the voluntary registers and population based studies have onsistently shown that psyhiatri symptoms 4 7 and mental disorders, 28 are more ommon in Gulf veterans than non-gulf ontrols. A signifiant proportion of veterans on the voluntary register who had reeived a symptoms, signs, and ill-defined ondition diagnosis had a psyhiatri disorder, either depression, somatoform disorder, tension headahes, or post-traumati stress disorder. A dose response assoiation between the number of symptoms reported and post-traumati stress disorder and depression in Gulf veterans has also been reported. The overall linial piture to date is that Gulf veterans are reporting more symptoms, whih appear to be multi organ and non-speifi. The most ommon symptoms are related to mood and ognitive funtioning and appear to diver from other military populations only in frequeny and severity. An important limitation of most studies is that they have used self report measures of illness as opposed to objetive measures; this inreases the risk of reall bias and inadvertent endorsement of symptom in the questionnaires, and may have led to overestimation of health problems.

3 Eduation 756 * Gulf War speifi exposures A number of environmental fators speifi to the Gulf onflit suh as suspeted hemial weapons, organophosphate pestiides, immunisations, pyridostigmine bromide, oil well fires, and depleted uranium have been postulated as being linked to the syndrome. Several population based studies have reported assoiations between a wide range of self report exposures and ill health. 467 Depleted uranium is used in ammunition and armoury. A small group of soldiers were involved in handling depleted uranium whih was then exreted, but no health evets have been found; monitoring for late sequelae ontinues in this sample. Over 600 oil wells were set alight at the end of the ground war whih led to plumes of blak louds. Environmental monitoring studies at the time did not find exess levels of toxi gases suh as hydrogen sulfide and sulfur dioxide, but there was an inrease in the level of fine partiulate matter. Military personnel involved in bringing the fires under ontrol were appropriately proteted. 11 Smoke fire an ause eye and nose irritation and dereased pulmonary funtion. While respiratory symptoms are ommonly reported, the sparse data on objetive pulmonary funtion suggests that there is no objetive evidene of respiratory damage attributable to oil well smoke. 6 There was a real threat of nerve agents, suh as sarin, and blister agents, suh as mustard, being released by Iraq and hemial weapons alarms were in widespread use. There were frequent, sometimes several times a day, presumed false, alarms and on eah oasion personnel were required to put on nulear-biologial-hemial (NBC) suits whih were unomfortable and indued partial sensory deprivation. There was an aidental destrution of an Iraqi arms dump with release of hemial agents at Khamisiyah but no asualties were reported at the time, 11 and there was no post-war inrease in hospitalisations in those who have possibly been exposed. Despite the lak of objetive evidene of widespread exposure to hemial weapons, the urrent state of knowledge is that, although unlikely, there is insuyient evidene to rule out that short periods of sublethal doses of sarin may ause neurologial damage. 11 Pyridostigmine bromide was used as pre-treatment for possible exposure to nerve gas. It ats by inhibiting holinesterase at the neuromusular juntion; the atual doses, frequeny, and duration of pyridostigmine bromide administered varied from unit to unit. Some investigators have suggested that pyridostigmine bromide may be a andidate exposure beause some individuals are genetially more suseptible to pyridostigmine bromide and/or it may have ated synergistially with pestiides. 12 Animal models have suggested that stress may inrease blood brain barrier permeability to pyridostigmine bromide, although this has been hallenged. Self report pyridostigmine bromide intake was not assoiated with post war handgrip strength. Pyridostigmine bromide is used in muh higher doses for patients with myasthenia gravis whih suggests it is unlikely to have been toxi to Gulf veterans. Varying amounts of pestiides were issued (DEET and premethrin) to ombat the desert pests that inhabited the military amps with personnel. While there is usually gross evidene of toxi evets of high doses of organosphophates, the delayed evets of hroni low level exposure, perhaps in onjuntion with pyridostigmine bromide, are not known. There was also a real threat of biologial weapons, namely anthrax, plague, and botulinum. The UK programme involved immunisations against plague, with pertussis to aelerate the immune response, and anthrax. The US programme involved immunisations against anthrax and botulinum. Personnel reeived the vainations either before deployment or on arrival in the Gulf theatre. Regular vainations in the military are a ommon pratie but immunisation against biologial weapons is rare, leading to speulation that multiple vainations may have damaged the immune system. Rook and Zumla hypothesised that the regimen of multiple vainations given to Gulf veterans during stress, espeially the administration of pertussis, may have interated with pestiides to ause a shift in the T ell ytokine profiles from Th1 to Th2, whih may have led to symptom development 13 (fig 2). Reeiving multiple vaines during deployment but not before deployment was assoiated with multiple symptoms in UK Gulf veterans and lends some support to this theory. 14 The evidene to date suggests that there are serious biases that may invalidate the reported assoiations between exposures and ill health. Most of the exposures have been assessed using self report measures and are now objetively unmeasurable. The alleged exposures were not systemially measured in the Gulf theatre. Potential interations between various exposures remain poorly understood. Box 3: Gulf speifi exposures Using self report measures, a wide range of Gulf speifi exposures have been found to be assoiated with ill health There is insuffiient objetive evidene for any one exposure Long term effets of low doses of postulated toxins, suh as hemial agents, depleted uranium, and pestiides are unertain but are unlikely to play an important aetiologial role in the development of symptoms Role of stress The US Presidential Advisory Committee onluded that among other fators, stress was likely to be an important ontributing fator to Gulf War related illnesses. Similar syndromes have arisen from previous onflits. These onditions have reeived many diverent labels: soldier s heart and evort syndrome were borne from the Crimean war, shell shok and neurasthenia from the first world war, and Agent Orange syndrome following the Vietnam war. 16 These wars were horrifi in the toll of human lives and the extreme living onditions. No physial ause was found for the health problems, and the psyhologial impat of onflit began to be inreasingly reognised. Post-traumati stress disorder emerged as a diagnosable ondition following the Vietnam war, in an attempt to reognise the role of extreme stress in the development of ertain mental health problems. There is also inreasing evidene that physial symptoms and onditions are ommon in people with post-traumati stress disorder. The symptoms in Gulf veterans are similar to symptoms in other onflits in that they share fatigue, shortness of breath, headahe, sleep diyulties, impaired onentration, and forgetfulness. 16 On first impressions, the Gulf War annot ompare with human asualties and settings of previous onflits. On loser inspetion, Gulf veterans were under onsiderable stress. The threat of biologial and hemial warfare was real, onstant, and serious and the assoiated fear annot be underestimated. It has been argued that biologial and hemial agents are as muh psyhologial as physial weapons.

4 Eduation Th1 IL-2 IFNγ Classial ell mediated immunity, and marophage ativation Help for ytotoxi T ells *757 Vaines Th0 Multiple, simultaneous vainations Pertussis as adjuvant Th2 IL-4 IL-5 Cutaneous basophil hypersensitivity Inreased eosinophils and mast ells, hayfever, allergi asthma Figure 2 The Rook and Zumula 13 theoretial model of a potential effet of multiple vaine on immune funtion. Similar syndromes have also been identified in the ivilian population. A number of multi symptom, medially unexplained syndromes are very similar to those found in Gulf veterans. These onditions are hroni fatigue syndrome, total allergy syndrome, dental amalgam disease, hroni Lyme disease, sik building syndrome, multiple hemial sensitivity, fibromyalgia, and irritable bowel syndrome. These symptoms and onditions tend to overlap with eah other 17 and are ommonly assoiated with mood. They tend to be similar in that no physial ause an be identified and stressful events are assoiated with their onset. They tend to diver in the aetiologial attribution of the ondition given by the patient and the media, from viruses to hemials to buildings, in the ontext of inadequate epidemiologial or biologial evidene for a ausal relationship. Elevated rates of hroni fatigue syndrome and multiple hemial sensitivity have been reported in Gulf veterans. Other explanatory fators Soiodemographi risk fators that pertain to many health problems in the ivilian populations, suh as soioeonomi status and lifestyles, appear to be relevant to ill health in Gulf veterans. Privates were around 20% more likely to report ill health than non-ommissioned oyers and around 70% more likely to report ill health than oyers. Ex-servie Gulf veterans were around two times more likely to report Box 4: Non-Gulf speifi exposures A number of non-gulf speifi exposures, suh as smoking, rank, ex-servie, have been assoiated with ill health in Gulf veterans Stress is likely to have played an important role in the aetiology of symptoms Symptoms in Gulf veterans appear to have some similarity with symptoms following previous onflits and in ivilian populations psyhologial and physial ill health, 18 perhaps beause they now adopted a more sedentary ivilian lifestyle. Smoking was also assoiated with ill health. Pre-deployment training, group ohesiveness, suh as the buddy system, and post-deployment leave have been onsidered important in preventing psyhiatri breakdown sine the seond world war. In one tentative survey, there was no evidene that proxy markers of these fators were important for ill health, exept perhaps in ombat units. 18 Soial and ultural values play a role in the emergene and aeptane of a new disorder. 1 Prevailing attitudes towards homosexuality interfered with the media and publi understanding of HIV and AIDS. Disorders defined by linial features as opposed to pathology, suh as depression and medially unexplained syndromes, are more vulnerable to having their definition distorted by the prevailing attitudes of soiety and the media. It is diyult to quantify the impat of war images and media information (fig 3) on the onset and appraisal of symptoms in Gulf veterans, but it is possible to speulate that for some Gulf veterans this may have led to attributing non-speifi symptoms to their experiene in the Gulf. 3 Treatments Interventions have been limited. In the light of no single identified fator or learly defined disease proess to treat, some liniians have suessfully used a multidisiplinary model based on the management of hroni pain. 19 The model of are would require forming a therapeuti relationship where the experiene of symptoms by the veterans is aknowledged by the liniian. This involves a detailed medial and psyhiatri assessment and investigations as appropriate to exlude physial and psyhiatri explanations for the symptoms. The patient should be enouraged to shift his pereption of his ondition from one of ause (as no single ause has been identified) to one of rehabilitation, as would be the ase with any other hroni ondition, suh as heart disease. The patient ould

5 Eduation 758 * Gulf War syndrome Part of the diyulty the Defense Department has had in determining any auses of so-alled Gulf War illnesses is the wide range of symptoms reported by U.S. troops and the fat no single fator an aount for their ailments. Here s a list of the most ommonly reported symptoms and some possible auses being investigated. Symptoms: Fatigue Joint pain Headahes Rashes/skin problems Insomnia Possible auses: Physial/psyhologial stress Low-level exposure to nerve gas Low-level exposure to biologial weapons Vaines given to soldiers Toxi fumes from burning oil wells Depleted uranium from munitions Pestiides Veterans who served in the Persian Gulf an all toll-free an information helpline at Figure 3 Example of a US media report (NBC News) on Gulf War syndrome. be enouraged to inrease his funtional apaity by partiipating in a graded exerise programme that he finds aeptable and promoting strategies that help him to not exessively fous on his symptoms. Any onurrent psyhiatri ondition typially depression, anxiety, post-traumati stress disorder, and alohol problems should be atively treated. Outome studies To date there have been very few outome studies that examine the ourse and persistene of symptoms in Gulf veterans, and to monitor the lateny period for an emerging illness. In a ohort of US Gulf veterans who were assessed soon after returning from the Gulf, the prevalene of post-traumati stress symptoms had inreased twofold two years later. Post-traumati stress symptoms were also assoiated with inreased somati symptoms two years later. A ase ontrol study nested within a randomly seleted ohort of US Gulf veterans reported that psyhologial symptoms and unexplained fatigue tend to persist but other symptoms, suh as musuloskeletal pain, gastrointestinal omplaints, and skin rashes, flutuate. These early results suggest that symptoms may have a delayed onset and follow a flutuating ourse. Other outome studies, suh as those run by the Gulf War Illnesses Researh Unit at King s College, London, are in progress. Methodologial problems The study of ill health in Gulf veterans has been limited by both avoidable and unavoidable methodologial problems. Studies that use seletive samples suh as veterans who are in urrent servie or in reserve units have limited generalisability. Studies that do not use a ontrol group annot make inferenes for a new disorder, as they have not tested whether similar problems are present in non-gulf samples. The use of self report measures, while the most pratial tool in large surveys, may risk overestimating health problems, so do need validating by objetive assessments. The time lag between the Gulf onflit and urrent researh ativities is over 10 years, suggesting that it is unlikely that any ausal inferene an be made from self report measures of exposures. Yet there are almost no objetive methods of measuring the various exposures. The evidene that some Gulf veterans are still reporting ill health annot be ignored and aetiologial models are still needed. Perhaps models that attempt to desribe the nature of ill health are one way forward. For example, an urrent ill health be explained by liniian evaluated psyhiatri disorders? Another ompliation of the time lag is traing Gulf veterans. Many of them have left the servies and put their military experiene behind them. Issues relating to onfidentiality an avet traking of urrent serving and disharged veterans. The soiodemographi harateristis of most military personnel that is, male, young, mobile, and of lower ranks makes them a more diyult group to trae. Box 5: Methodologial problems Time lag sine Gulf onflit ( ) and urrent health Reall bias of Gulf speifi exposures Need to use study samples that are representative of the population that was deployed to the Gulf Appropriate (other military) omparison groups need to be used to test differenes in health and exposures Lessons for the future Modern militaries are diverent to previous militaries: a greater proportion omprises ombat support and other support servies units and a smaller proportion of ombat units; highly advaned tehnologies are used whih are not without their own risks; and peaekeeping and managing human suvering are inreasingly playing a role. Post-onflit health problems are likely to ontinue to emerge. The main aim of military organisations should be prevention. The mehanisms urrently available are risk ommuniation, olletion of routine data, and ommissioning researh. Risk ommuniation strategies applied to ivilian populations may need to be onsidered by military organisations to develop further their own well established risk ommuniation. 20 EVetive risk ommuniation involves providing a balane between the amount, timing, and setting of dissemination. DiVerent organisations need to onsider strategies appropriate to them, but the key omponents of risk ommuniation involves identifying the risk(s) that need to be onveyed, understanding the target audiene(s), seleting the hannels and methods by whih the messages will be disseminated, implementing the ommuniations, and assessing feedbak. In future onflits personnel ould be eduated about the physial and mental evets of deployment rather than solely on obvious life events suh as ombat. One of the reurrent diyulties in establishing ausal links between Gulf speifi exposures and subsequent ill health has been the lak of valid exposure data. Future deployments will require planning to measure potential environmental risk fators. Some measures are related to logistis, suh as medial reord keeping in and out of field hospitals. Pre-deployment standardised examinations will provide baseline health data from whih prospetive studies an be mounted. Potential environmental risk fators for eah onflit zone should be atively sought and measured at baseline. The initial relutane of governments to aknowledge a health problem led to onspiray theories by the media and veterans group. 311 As publi and media onern about speifi exposures are unpreditable, military organisations and governments need to be prepared to at swiftly by ommissioning researh early and setting up evaluation entres.

6 Eduation Finally, researh is still ongoing. In the UK, three population based projets (University of Manhester, King s College, and the London Shool of Hygiene and Tropial Mediine) ontinue to generate epidemiologial data on aetiology and outome of UK Gulf veterans. The USA ontinues to invest into geneti, immunologial, toxiology, linial, and epidemiologial researh studies and the results will ontinue to be published for years to ome. Box 6: Future onflits Surveillane and medial reord keeping during deployments should be a key strategy in deteting and preventing health problems Implementing researh earlier rather than later should be enouraged Strategies to improve risk ommuniation will beome inreasingly important Conlusions Gulf veterans do have inreased health problems. At present, they appear to have a linial profile related to other medially unexplained onditions, suh as hroni fatigue syndrome. No single aetiologial fator has been identified and it is likely that Gulf war related ill health is aused by a omplex interation of multiple fators, suh as stress, vainations, and soietal fators. The main lesson for the future is to prevent post-onflit health problems by employing multiple approahes, using risk ommuniation, surveillane, and ommissioning researh. To date, there is no onsistent evidene of a syndrome unique to Gulf veterans. The ontroversy reminds us that militaries are made up of individuals whose oupation is to protet the rights of itizens in their own, and in other nations, often in extreme onditions. Referenes 1 Wegman D, Woods N, Bailar J. Invited ommentary: How would we know a Gulf war syndrome if we saw one? Am J Epidemiol 1997;146: This is an exellent desription of the methodologial issues in assessing emerging disorders. 2 Joseph S, and the Comprehensive Clinial Evaluation Program Evaluation Team. A omprehensive linial evaluation of Persian Gulf war veterans. Milit Med 1997;162: Wessely S, Chalder T, Davies K, et al. Ten years on: what do we know about Gulf war syndrome? In: Havenaar J, ed. Health onsequenes of eologial disasters. (in press) This is an exhaustive review of the epidemiologial and biologial data published to date as well as an opinion on the ultural fators involved in the emergene of new disorders. 4 The Iowa Persian Gulf Study Group. Self-reported illnesses and health status among Gulf war veterans. A population based study. JAMA 1997;277: Fukuda K, Nisenbaum R, Stewart G, et al. Chroni multi-symptom illness affeting Air Fore veterans of the Gulf war. JAMA 1998;280: Gray G, Kaiser K, Hawksworth A, et al. Inreased postwar symptoms and psyhologial morbidity among US Navy Gulf war veterans. Am J Trop Med Hygiene 1999;60: Unwin C, Blathley N, Coker W, et al. Health of UK serviemen who served in the Persian Gulf war. Lanet 1999;353: This was the first UK based population study using two ontrol groups. It onfirmed earlier US findings and established that there was an inrease in symptoms in UK Gulf veterans. 8 Gray G, Coate B, Anderson C, et al. The postwar hospitalization experiene of US veterans of the Persian Gulf war. N Engl J Med 1996;335: Mafarlane G, Thomas E, Cherry N. Mortality among UK Gulf war veterans. Lanet 2000;356: This is a well designed and implemented UK based population study of the mortality rates in UK Gulf veterans. 10 Ismail K, Everitt B, Blathley H, et al. Is there a Gulf war syndrome? Lanet 1999;353: Presidential Advisory Committee on Gulf War Veterans Illnesses. Final report. Washington, DC: US Government Printing Offie, This report is an exellent summary of the evidene of health problems and the exposures. It makes reommendations and reports the opinions of various individuals and organisations. It is an example of how an enquiry should be onduted. 12 Institute of Mediine. Gulf war and health: volume 1. Depleted uranium, pyridostigmine bromide, sarin, and vaines. Washington DC: National Aademy Press, This is part of a series of exhaustive reports summarising Gulf and non-gulf evidene for the health effets of various exposures. It an be obtained free from the website < 13 Rook G, Zumla A. Gulf war syndrome: is it due to a systemi shift in ytokine balane towards a Th2 profile? Lanet 1997;349: This is a pioneering theoretial paper whih proposes how multiple psyhologial and biologial stresses ould potentially lead to immune hanges. 14 Hotopf M, David A, Hull L, et al. Role of vainations as risk fators for ill health in veterans of the Gulf war: ross setional study. BMJ 2000;320: Marshall G, Davis L, Sherbourne C. A review of the sientifi literature as it pertains to Gulf war illnesses, volume 4: stress. Santa Monia, California: RAND Health, 2000 <http//rand.org>. This is an exhaustive review of stress and its health effets using evidene from ivilian and military populations. It an be obtained free from the website. 16 Hymans K, Wignall S, Roswell R. War syndromes and their evaluation: from the US ivil war to the Persian Gulf war. Ann Intern Med 1997;125: This is a seminal and highly readable paper reviewing Gulf War health in the ontext of other post onflit health problems. 17 Wessely S, Nimnuan C, Sharpe M. Funtional somati syndromes: one or many? Lanet 1978;354: Ismail K, Blathley N, Hotopf M, et al. Oupational risk fators for ill health in UK Gulf veterans. J Epidemiol Community Health 2000;54: Engel CCJ, Roy M, Kayanan D, et al. Multidisiplinary treatment of persistent symptoms after Gulf war servie. Mil Med 1998;163: Institute of Mediine. Strategies to protet the health of deployed U.S. fores: medial surveillane, reord keeping, and risk redution. Washington DC: National Aademy Press, This is a well written and thoughtful report on various strategies to derease the likelihood of health problems in future onflits. It an be obtained on the website < *759

7 Eduation 760 * QUESTIONS (See answers on p 715) (1) Whih of the following statements about symptoms in Gulf War related ill health is orret? (a) Symptoms are rarely assoiated with psyhiatri disorders (b) Symptoms fall into a unique luster that is different to other disorders () One of the most ommonly reported symptom is headahe (d) Symptoms that are ommon in Gulf veterans are as ommon in veterans not deployed to the Gulf (e) As a group Gulf veterans are severely physially impaired (2) A variety of researh methods have been used in the study of Gulf War related ill health. Whih of the following methods is most likely to provide data based on samples that are representative of those who served in the Gulf onflit? (a) Case series (b) Voluntary registries () Seleted military units of personnel in urrent servie (d) Population based ross setional studies (e) Outome studies (3) Whih of the following is a orret interpretation of the urrent evidene regarding exposures? (a) Stress is most likely to be the single most important fator in the development of symptoms (b) The effets of depleted uranium on brain damage are well known () The levels of pestiides used were suffiiently high to be regarded as toxi (d) It is unlikely that biologial and hemial weapons were released (e) Multiple vainations are assoiated with inreased psyhologial problems (4) Whih of the following statements is orret? (a) There is good evidene that the media has ontributed to the emergene of a Gulf War syndrome (b) Medially unexplained syndromes are inreased in Gulf veterans () The more deployments a soldier has the more likely he is to develop health problems (d) Modern onflits are less stressful than previous onflits (e) Most of the symptoms in Gulf War veterans an be explained by post-traumati stress disorder (5) In future onflits: (a) One of the objetives in risk ommuniation is to assume that the intended audienes have the same harateristis (b) Compensation should be given earlier rather than later, even if the medial ondition is not yet learly defined () Routine surveillane of deployed personnel would be a useful method of olleting baseline data (d) Commissioning researh should be delayed until there is lear evidene of a health problem (e) There is no longer any need to promote group ohesiveness in military units