Persistence of symptoms in veterans of the first Gulf War: 5-year follow-up.BACKGROUND: During the 1990-1991 Gulf War, approximately 700,000 U.S. troops were deployed to the Persian Gulf Persian Gulf, arm of the Arabian Sea, 90,000 sq mi (233,100 sq km), between the Arabian peninsula and Iran, extending c.600 mi (970 km) from the Shatt al Arab delta to the Strait of Hormuz, which links it with the Gulf of Oman. theater of operations Noun 1. theater of operations - a region in which active military operations are in progress; "the army was in the field awaiting action"; "he served in the Vietnam theater for three years" field of operations, theatre of operations, theater, theatre, field . Of that number, approximately 100,000 have presented medical complaints through various registry and examination programs. OBJECTIVES: Widespread symptomatic symptomatic /symp·to·mat·ic/ (simp?to-mat´ik) 1. pertaining to or of the nature of a symptom. 2. indicative (of a particular disease or disorder). 3. illness without defining physical features has been reported among veterans of the 1991 Gulf War. We ascertained as·cer·tain tr.v. as·cer·tained, as·cer·tain·ing, as·cer·tains 1. To discover with certainty, as through examination or experimentation. See Synonyms at discover. 2. changes in symptom symptom /symp·tom/ (simp´tom) any subjective evidence of disease or of a patient's condition, i.e., such evidence as perceived by the patient; a change in a patient's condition indicative of some bodily or mental state. status between an initial 1995 symptom evaluation and a follow-up in 2000. METHODS: We assessed mailed symptom survey questionnaires for 390 previously surveyed members of the U.S. Department of Veterans Affairs Veterans Affairs is a term of the business that deals with the relation between a government and its veteran communities, usually administered by the designated government agency. Gulf War Registry for changes over the 5-year interval in terms of number and severity of symptoms. RESULTS: For the cohort cohort /co·hort/ (ko´hort) 1. in epidemiology, a group of individuals sharing a common characteristic and observed over time in the group. 2. as a whole, we found no significant changes in symptom number or severity. Those initially more symptomatic in 1995 showed some improvement over time, but remained much more highly symptomatic than those who had lesser initial symptomatology symptomatology /symp·to·ma·tol·o·gy/ (simp?to-mah-tol´ah-je) 1. the branch of medicine dealing with symptoms. 2. the combined symptoms of a disease. symp·to·ma·tol·o·gy n. . CONCLUSIONS: The symptom outbreak following the 1991 Gulf War has not abated Abated, an ancient technical term applied in masonry and metal work to those portions which are sunk beneath the surface, as in inscriptions where the ground is sunk round the letters so as to leave the letters or ornament in relief. From 1911 Encyclopædia Britannica over time in registry veterans, suggesting substantial need for better understanding and care for these veterans. KEY WORDS: Gulf War illness, medically unexplained unexplained Adjective strange or unclear because the reason for it is not known Adj. 1. unexplained - not explained; "accomplished by some unexplained process" symptoms. Environ en·vi·ron tr.v. en·vi·roned, en·vi·ron·ing, en·vi·rons To encircle; surround. See Synonyms at surround. [Middle English envirounen, from Old French environner Health Perspect 114:1553-1557 (2006). doi:10.1289/ehp.9251 available via http://dx.doi.org/ [Online 6 July 2006] ********** During the 1990-1991 Gulf War (GW), approximately 700,000 U.S. troops were deployed to the Persian Gulf theater of operations. Large-scale involvement of U.S. forces in combat in this region largely ended by the winter of 1991. Nevertheless, significant numbers of the 700,000 U.S. service personnel deployed to the region in 1990-1991 presented with medical complaints in the years following operations. Of that number, approximately 100,000 have presented medical complaints through various registry and examination programs (Brown et al. 2002; Stuart et al. 2002). The symptomatology that characterizes their complaints has been described in a number of studies, including investigations from the United Kingdom and other countries (Iowa Persian Gulf Study Group 1997; Lashof and Cassells 1998; Perisan Gulf Veterans Coordinating Board 1995; Unwin et al. 1999). These studies of both randomly sampled and selected populations show that GW veterans clearly report both increased numbers and severity of virtually all symptoms queried when compared with personnel not deployed to the region. Significantly, to date, these symptoms are not reliably associated with characteristic signs or diagnoses of pathological 1. pathological - [scientific computation] Used of a data set that is grossly atypical of normal expected input, especially one that exposes a weakness or bug in whatever algorithm one is using. conditions (Eisen et al. 2005; Fukuda et al. 1998; Hodgson and Kipen 1999; Wessely 2004). Only one study has made an attempt to longitudinally lon·gi·tu·di·nal adj. 1. a. Of or relating to longitude or length: a longitudinal reckoning by the navigator; made longitudinal measurements of the hull. b. follow GW veterans to determine how their symptomatic presentations have evolved--whether there has been improvement, stability, or decline in the self-reported health of individuals and groups of GW veterans (Hotopf et al. 2003, 2004). This information is critical in trying to understand not just the etiology etiology /eti·ol·o·gy/ (e?te-ol´ah-je) 1. the science dealing with causes of disease. 2. the cause of a disease. of such complaints but also how to plan for continued care and rehabilitation rehabilitation: see physical therapy. . We have studied, both clinically and by survey, various groups of GW veterans since 1995 (Fiedler et al. 2006; Hallman et al. 2003; Kipen et al. 1999; Peckerman et al. 1999; Pollet et al. 1998). Our original investigations were from a random sample of the Department of Veterans Affairs (VA) GW registry members. We found that physician diagnoses, including those without a generally accepted etiology such as chronic fatigue syndrome chronic fatigue syndrome (CFS), collection of persistent, debilitating symptoms, the most notable of which is severe, lasting fatigue. In other countries it is known variously as myalgic encephalomyelitis, chronic fatigue and immune dysfunction syndrome, and , multiple chemical sensitivities multiple chemical sensitivity (MCS), adverse physical reaction to certain chemicals in susceptible persons. When exposed to the chemicals, people with MCS react with symptoms such as nausea, headache, dizziness, fatigue, impaired memory, rash, and respiratory , and fibromyalgia fibromyalgia Chronic syndrome that is characterized by musculoskeletal pain, often at multiple sites. The cause is unknown. A significant number of persons with fibromyalgia also have mental disorders, especially depression. , could not account for much of the symptomatology presented and that, based on symptom endorsement and severity, veterans on the registry could be robustly classified as either highly symptomatic (40% of subjects) or mildly symptomatic (60% of subjects) (Hallman et al. 2003). The large number of highly symptomatic "cases" (i.e., self-reported sick individuals), as well as representation from all four service branches, including National Guard and Reserve units, makes the VA registry a robust population from which to investigate the characteristics, although not the prevalence, of GW illnesses. We are currently studying more representative random populations of GW veterans (Fiedler et al. 2006). As part of this random sample of deployed and nondeployed veterans surveyed in 2000, we took advantage of the opportunity to do a 5-year follow-up of our original cohort of individuals from the registry. We hypothesized that the symptom reporting would remain relatively constant over the 5-year frame and that the highly symptomatic cluster would show a greater tendency toward decline in their health status (more symptomatology) after controlling for demographic variables. Materials and Methods Participants. Participants were U.S. military veterans from the Gulf War Health Registry maintained by the VA. In 1995 (time 1), veterans residing in seven states--Delaware, Illinois, New Jersey, New York New York, state, United States New York, Middle Atlantic state of the United States. It is bordered by Vermont, Massachusetts, Connecticut, and the Atlantic Ocean (E), New Jersey and Pennsylvania (S), Lakes Erie and Ontario and the Canadian province of , North Carolina North Carolina, state in the SE United States. It is bordered by the Atlantic Ocean (E), South Carolina and Georgia (S), Tennessee (W), and Virginia (N). Facts and Figures Area, 52,586 sq mi (136,198 sq km). Pop. , Ohio, and Pennsylvania--were selected by VA's Environmental Epidemiology epidemiology, field of medicine concerned with the study of epidemics, outbreaks of disease that affect large numbers of people. Epidemiologists, using sophisticated statistical analyses, field investigations, and complex laboratory techniques, investigate the cause Service using a simple random sampling procedure. The veterans were originally selected as part of recruitment for clinical studies of GW illness (Hallman et al. 2003; Nelson et al. 2001; Pollet et al. 1998). A random subset A group of commands or functions that do not include all the capabilities of the original specification. Software or hardware components designed for the subset will also work with the original. of veterans who completed that survey formed the sampling frame for the present study conducted in 2000 (time 2). Procedure. At time 1, we mailed introductory letters and questionnaires with postage-paid response envelopes to 2,011 veterans. We followed this with reminder postcards, a second (identical) letter and questionnaire, and a maximum of three follow-up phone calls at intervals coming or happening with intervals between; now and then. See also: Interval of approximately 2 weeks until a response was received, ultimately yielding 1,161 responses (60%). At time 2, The U.S. Department of Defense's Defense Manpower Data Center The Defense Manpower Data Center (DMDC) serves under the Office of the Secretary of Defense to collate personnel, manpower, training, financial, and other data for the Department of Defense. (DMDC DMDC Defense Manpower Data Center DMDC Defense Management Data Center DMDC Disk Memory Drive Controller ) provided updated addresses and demographic information on those who had responded at time 1. These veterans were sent a letter describing the project and requesting their consent to be interviewed. Records from the Internal Revenue Service and national directory assistance databases (e.g., TeleMatch, Springfield, VA) were used to locate veterans whose letters were returned without forwarding information. These databases did not include cellular telephone numbers. This 5-year follow-up of the registry cohort was included as a part of a larger investigation of a national random sample of deployed GW veterans (Fiedler et al. 2006). As part of this study, after informed consent was obtained, all subjects were interviewed by a computer-assisted telephone interview (CATI CATI Computer-Assisted Telephone Interviewing CATI California Agricultural Technology Institute CATI Center for Advanced Technology & Innovation CATI Carolina Association of Translators & Interpreters ) method. However, to allow direct follow-up comparisons to the data collected by mail at time 1 and to compare data collection modalities Modalities The factors and circumstances that cause a patient's symptoms to improve or worsen, including weather, time of day, effects of food, and similar factors. , 60% of those in our original registry cohort were randomly mailed a one-page questionnaire, comprising only symptom questions, 2 weeks before their telephone interview (Brewer et al. 2004). The veterans reported an average of five more symptoms via mail than via telephone, mainly as the result of mild symptoms reported by mail that were not reported at all during the telephone interview (Brewer et al. 2004). As a result, we used this one-page written symptom questionnaire as the basis of our comparisons. Additional demographic and other health information was collected as part of the subsequent CATI interview. Measures. Participants were asked to examine a list of 48 symptoms identical to that used at time 1 (Table 1). For each symptom, the respondents In the context of marketing research, a representative sample drawn from a larger population of people from whom information is collected and used to develop or confirm marketing strategy. indicated whether they had experienced "persistent or recurring re·cur intr.v. re·curred, re·cur·ring, re·curs 1. To happen, come up, or show up again or repeatedly. 2. To return to one's attention or memory. 3. To return in thought or discourse. " problems within the last 6 months, and if so, whether the problems they had experienced were "mild," "moderate," or "severe." For each symptom, a severity index was calculated by coding "no" as 0, "mild" as 1, "moderate" as 2, and "severe" as 3. Based on factor and cluster analyses of their time 1 symptom data, each respondent In Equity practice, the party who answers a bill or other proceeding in equity. The party against whom an appeal or motion, an application for a court order, is instituted and who is required to answer in order to protect his or her interests. had been classified as belonging to one of two clusters: a) veterans reporting good health and few moderate/severe symptoms (n = 242; ~ 60%), and b) veterans reporting fair/poor health and endorsing an average of 37 symptoms, 75% as moderate/severe (n = 148; ~ 40%). Thus, there was a total of 390 respondents who completed both the time 1 and time 2 symptomatology assessments (Table 2) (Hallman et al. 2003). Statistical analyses. To assess changes in symptoms over time, we conducted paired samples t-tests on the average number of symptoms and average severity of symptoms endorsed at time 1 and time 2. We performed repeated measures MANCOVA MANCOVA Multivariate Analysis of Covariance (multiple analysis of covariance Covariance A measure of the degree to which returns on two risky assets move in tandem. A positive covariance means that asset returns move together. A negative covariance means returns vary inversely. ) to examine the main effect of time on the severity of 48 symptoms by controlling for age (mean centered), rank, race, marital status marital status, n the legal standing of a person in regard to his or her marriage state. , sex, education, branch of service, duty (active or National Guard/Reserve), smoker smoker A person who smokes tobacco, almost always understood to be cigarettes Ratio of ♂:♀ smokers Philippines64/19, China61/7, Saudi Arabia53/2, Russia50/12 status, and cluster membership ("mildly" or "highly" symptomatic as classified at time 1). In addition, we performed an ANCOVA ANCOVA Analysis of Covariance (analysis of covariance) to examine the main effect of cluster membership at time 1 on change in number of symptoms over the 5-year period. The change score was calculated by subtracting time 1 scores from time 2 scores. We used the following variables as controls: age (mean centered), sex, rank, race, marital status, education, branch, duty, and smoking status. For tests of main effects and interactions, we adopted p < 0.05 as the critical value. To adjust for multiple comparisons when comparing changes in the 48 individual symptoms, we employed a Bonferroni correction In statistics, the Bonferroni correction states that if an experimenter is testing n independent hypotheses on a set of data, then the statistical significance level that should be used for each hypothesis separately is 1/n , adopting as a critical value p < 0.001 (0.05/48). Results Response rates. Time 1. The results for time 1 have been fully described by Hallman et al. (2003). Of the 1,935 deliverable questionnaires, 1,161 were completed and returned by the respondents, yielding a response rate of 60%. Using chi-square analyses, we tested for potential selection biases and found no significant differences in the distribution of branch of service, duty status (active, Reserve, National Guard), or sex between those randomly selected to be in the sample and those in the registry as a whole. Logistic regression In statistics, logistic regression is a regression model for binomially distributed response/dependent variables. It is useful for modeling the probability of an event occurring as a function of other factors. analyses suggested no significant differences in response rates attributable to sex, date of entry into the registry, branch of service, type of duty (active, Reserve, or National Guard), or rank [enlisted en·list·ed adj. Of, relating to, or being a member of a military rank below a commissioned officer or warrant officer. enlisted Adjective , noncommissioned officer non·com·mis·sioned officer n. Abbr. NCO An enlisted member of the armed forces, such as a corporal, sergeant, or petty officer, appointed to a rank conferring leadership over other enlisted personnel. (NCO NCO abbr. noncommissioned officer NCO noncommissioned officer NCO n abbr (Mil) (= noncommissioned officer) → Uffz. ), warrant officer, officer]. Multivariate analysis multivariate analysis, n a statistical approach used to evaluate multiple variables. multivariate analysis, n a set of techniques used when variation in several variables has to be studied simultaneously. of variance also revealed no significant differences in response rates attributable to either specific symptoms or specific diagnoses as determined by VA examining physicians and independent questionnaires completed at the time of registry enrollment (generally, months to years prior to time 1 study). Time 2. Updated DMDC data and data collected by telephone indicated that 70 of the original 1,161 registry veterans were ineligible in·el·i·gi·ble adj. 1. Disqualified by law, rule, or provision: ineligible to run for office; ineligible for health benefits. 2. to participate in the follow-up study. These included veterans who were deceased (n = 20), not deployed to the Gulf (n = 39), incarcerated incarcerated /in·car·cer·at·ed/ (in-kahr´ser-at?ed) imprisoned; constricted; subjected to incarceration. in·car·cer·at·ed adj. Confined or trapped, as a hernia. (n = 3), or incapacitated in·ca·pac·i·tate tr.v. in·ca·pac·i·tat·ed, in·ca·pac·i·tat·ing, in·ca·pac·i·tates 1. To deprive of strength or ability; disable. 2. To make legally ineligible; disqualify. (e.g., loss of hearing; n = 8). Of the remaining 1,091 eligible to participate, 640 (60%) were mailed a questionnaire, of which, 453 (71%) were completed and returned. Forty-five (7%) could not be delivered, and no forwarding address forwarding address forward n → adresse f de réexpédition could be found. Of those who completed the questionnaire, 426 were contacted by telephone and by mail, and 398 of these completed both time 1 and time 2 assessments. Thus, 62% of those mailed a questionnaire at time 2 completed it and the subsequent telephone interview. Eight cases were excluded because of missing data or because the demographic categories to which they belonged were too small to permit meaningful analyses. These included three veterans who served in the Coast Guard, one widowed veteran, three who indicated the "other" category for race, and one for whom rank was unknown, leaving 390 subjects for further analysis. These 390 respondents did not differ significantly from the 1,161 respondents who participated at time 1 in terms of sex (8.5% females vs. 9.6% of total); rank (12.6% officers vs. 10.1% of total); duty status at mobilization mobilization Organization of a nation's armed forces for active military service in time of war or other national emergency. It includes recruiting and training, building military bases and training camps, and procuring and distributing weapons, ammunition, uniforms, (57.5% active vs. 59.0% of total); or branch (70.0% Army vs. 70.2% of total). They were significantly different from the 1,161 originally studied in terms of age at time 2 (42.7 years vs. 41.7 years for total), racial composition (16.9% African American African American Multiculture A person having origins in any of the black racial groups of Africa. See Race. vs. 23.2% of total; p < 0.006, two-sided), and education (22.8% college graduates vs. 19.1% of total; p < 0.02). In addition, t-tests with Bonferroni correction revealed no significant differences in the number of symptoms or their average severity reported at time 1 by the 390 current respondents and the remainder of the time 1 cohort. Change in number of reported symptoms over time. At time 1, the mean number of symptoms ([+ or -] SD) reported by the sample of 390 was 22.07 [+ or -] 12.92. At time 2, the mean number of symptoms increased slightly (0.67 symptoms) to 22.74 [+ or -] 12.89; however, this change was not significant [t(389) = -1.48; p = 0.14]. Average symptom severity also increased slightly from 0.83 [+ or -] 0.62 at time 1 to 0.84 [+ or -] 0.62 at time 2. Again, this change was not significant [t(398) = -0.52; p = 0.61]. Results of ANCOVA on change in number of symptoms controlling for age (mean centered), sex, rank, race, marital status, education, branch, duty, and smoking status revealed that the effect of time 1 cluster membership was significant [F(1, 379) = 31.84; p < 0.001] (Table 3). Those veterans classified as mildly symptomatic at time 1 showed an increase in number of symptoms over time (mean, 2.33), and those veterans who were highly symptomatic showed a decrease in symptoms at time 2 (mean, -2.04). Also, there were significant effects of race [F(1, 379) = 15.11; p < 0.001] and age [F(1, 379) = 6.98; p < 0.05]. Black veterans reported 4.26 more symptoms at time 2, whereas white veterans showed a slight decrease [t (388) = -3.62; p < 0.001]. Increase in the number of symptoms over time was associated with older age (r = 0.12; p < 0.05). Changes in symptom severity over time. A repeated measures MANCOVA indicated that there was no significant difference over time in the severity of the 48 symptoms. However, we observed multivariate The use of multiple variables in a forecasting model. effects on severity for age [Wilks's [LAMBDA The Greek letter "L," which is used as a symbol for "wavelength." A lambda is a particular frequency of light, and the term is widely used in optical networking. Sending "multiple lambdas" down a fiber is the same as sending "multiple frequencies" or "multiple colors. ] = 0.756; F(48, 332) = 2.24; p < 0.001], race [Wilks's [LAMBDA] = 0.803; F (48, 332) = 1.70; p < 0.005], and cluster membership [Wilks's [LAMBDA] = 0.344; F(48, 332) = 13.19; p < 0.001] (Table 1). In addition, there was a significant time x smoker status effect [Wilks's [LAMBDA] = 0.815; F(48, 332) = 1.57; p < 0.05] and a significant time x cluster membership effect [Wilks's [LAMBDA] = 0.790; F (48, 332) = 1.84; p < 0.005]. Next, we looked at tests of between-subject effects for the variables that yielded significant multivariate tests to examine the severity changes in individual symptoms. The main effect of age was significant for "persistent or recurring problems" with "arms, hands, and shoulders," "back problems," "frequent or painful urination urination Process of excreting urine from the bladder (see urinary system). Nerve centres in the spinal cord, brain stem, and cerebral cortex control it through involuntary and voluntary muscles. The need to void is felt when the bladder holds 3. ," "sexual or genital genital /gen·i·tal/ (jen´i-t'l) 1. pertaining to reproduction, or to the reproductive organs. 2. (in the plural) the reproductive organs. gen·i·tal adj. 1. problems," "pain in arms armed for war; in a state of hostility. See also: Arms or legs," and "pain in more than one joint," with the severity of all these symptoms increasing more in older individuals. The main effect of race was significant for "persistent or recurring problems" with "constipation constipation, infrequent or difficult passage of feces. Constipation may be caused by the lack of adequate roughage or fluid in the diet, prolonged physical inactivity, certain drugs, or emotional disturbance. ," "hair," and "sweating not due to exercise," with all three symptoms increasing more in severity among African-American veterans (Table 4). The main effect of cluster membership was significant for "persistent or recurring problems" with all 48 symptoms at the p < 0.001 level, with F(1, 379) values ranging from 32.96 to 329.59. Veterans who were highly symptomatic at time 1 had higher severity scores at time 2 than those who reported mild symptomatology. The time x smoker status interaction term revealed that it was significant for "persistent or recurring problems" with "mouth, teeth, gums" (Table 4). Paired samples t-tests showed that while the changes in this symptom were not significant for those who never smoked and for former smokers, the increase in symptom severity for the current smokers was significant [t(100) = -3.37; p < 0.005]. The time x cluster membership interaction term was significant for "persistent or recurring problems," with 18 symptoms listed in Table 4. Paired samples t-tests for 18 symptoms for the cluster originally reporting mild symptomatology showed that after Bonferroni correction (0.05/18 = 0.002), the increases over time in the severity of "abdominal abdominal /ab·dom·i·nal/ (ab-dom´i-n'l) pertaining to the abdomen. ab·dom·i·nal adj. Of or relating to the abdomen. n. An abdominal muscle. gas," "muscle aches or cramps," "numbness numbness /numb·ness/ (num´nes) anesthesia (1). Numbness Loss of feeling or sensation. Mentioned in: Topical Anesthesia or tingling tin·gle v. tin·gled, tin·gling, tin·gles v.intr. 1. To have a prickling, stinging sensation, as from cold, a sharp slap, or excitement: tingled all over with joy. sensations," "pain in arms or legs," and "difficulty concentrating" were significant. For the cluster that reported high symptomatology at time 1, the decreases in the severity of "headaches," "difficulty breathing," "unrefreshing sleep," "sleeping more than usual," "sudden mood changes," and "feeling depressed or blue" were significant after Bonferroni correction (means [+ or -] SDs presented in Table 1). Discussion Consistent with our hypothesis, this group of Gulf War Registry veterans continued to experience significant symptoms 10 years after deployment to the Middle East, > 5 years after they presented for registry examination. In the cohort as a whole, we found no significant changes in individually matched symptom reporting, neither improvement nor progression, in number or severity of symptoms. However, some subgroups did show significant, albeit relatively small, changes. Important predictors of worsening wors·en tr. & intr.v. wors·ened, wors·en·ing, wors·ens To make or become worse. Noun 1. worsening - process of changing to an inferior state decline in quality, deterioration, declension included being less symptomatic at time 1, African-American race, older age, and being a smoker at time 2. The effects of older age and smoking seem logical based on their expected impact on musculoskeletal musculoskeletal /mus·cu·lo·skel·e·tal/ (-skel´e-t'l) pertaining to or comprising the skeleton and muscles. mus·cu·lo·skel·e·tal adj. Relating to or involving the muscles and the skeleton. changes and on oral health, respectively. However the effects of race and cluster are less straightforward. Those who were classified as highly symptomatic at time 1 had higher severity scores compared with those who were mildly symptomatic at both times. However, for 18 symptoms we did observe a time x cluster effect The cluster effect is the effect of buyers and sellers of a particular good or service congregating in a certain place and hence inducing other buyers and sellers to relocate there as well. ; this time x cluster effect showed that a subset of symptoms in mildly symptomatic people increased severity over time, whereas a distinct subset of symptoms in highly symptomatic people decreased severity over time. In spite of the increase in symptom number and severity for the mild cluster and the decrease for the high cluster, the individuals in the two groups still remain substantially apart and distinct, with high individuals maintaining high symptomatology over time. A history of physician diagnoses did not predict symptoms at time 1 (Hallman et al. 2003), so we did not include this data in these subsequent analyses. Prior medical evaluations of GW veterans have not demonstrated explanatory ex·plan·a·to·ry adj. Serving or intended to explain: an explanatory paragraph. ex·plan medical findings or diagnoses between those with and without symptoms (Eisen et al. 2005; Fukuda et al. 1998; Hodgson and Kipen 1999; Wessely 2004). Controlled trials controlled trial Clinical research A clinical study in which one group of participants receives an experimental drug while the other receives either a placebo or an approved–'gold standard' therapy. See Blinding, Double-blinded. of behavioral therapy behavioral therapy n. See behavior therapy. and antibiotics Antibiotics Definition Antibiotics may be informally defined as the subgroup of anti-infectives that are derived from bacterial sources and are used to treat bacterial infections. for Gulf War illness have been conducted, and some of our subjects likely participated in both routine and experimental therapies. However, based on reports from therapeutic trials to date, there is little reason to expect a large effect of treatment on symptoms (Donta 2004; Wessely 2004). Hotopf et al. (2003) measured total symptoms in a random-sample U.K. Gulf War veteran cohort in 1997 and again in 2001. They reported a nonsignificant non·sig·nif·i·cant adj. 1. Not significant. 2. Having, producing, or being a value obtained from a statistical test that lies within the limits for being of random occurrence. decrease in symptoms over the 4 years, consistent with our finding of only minor variation. Using a fatigue scale, a psychiatric psy·chi·at·ric adj. Of or relating to psychiatry. psychiatric adjective Pertaining to psychiatry, mental disorders distress scale (General Health Questionnaire) and a measure of physical function (Medical Outcome Study Short-Form 36), Hotopf et al. (2004) reported that greater initial severity of fatigue predicted greater severity for all three outcomes over a 5-year follow-up. This is somewhat contrary to our findings that more symptomatic individuals actually showed greater declines in symptomatology. This difference may be explained by their use of scales for specific conditions rather than unaggregated symptom data, as we used. They also found that the attribution at·tri·bu·tion n. 1. The act of attributing, especially the act of establishing a particular person as the creator of a work of art. 2. factor "Belief in Gulf War Syndrome Gulf War syndrome, popular name for a variety of ailments experienced by veterans after the Persian Gulf War. Symptoms reported include nausea, cramps, rashes, short-term memory loss, fatigue, difficulty in breathing, headaches, joint and muscle pain, and birth " was associated with worsening, which is consistent with our previous findings at time 1 (Boyd et al. 2003). Limitations. The veterans we studied were taken from a registry and thus may not be completely representative of all deployed soldiers. We did not have a comparison group that was not deployed in this analysis, but we used individual matching to avoid many sources of bias, and all analyses were adjusted for multiple potential demographic confounders. Self-report items are always subject to bias; also, the interpretation of symptoms in the absence of explanatory diagnoses remains a challenge, but cannot be avoided until more reliable biomarkers of such illnesses are developed. Implications. Overall, we found little change to indicate either a self-limited condition or one characterized char·ac·ter·ize tr.v. character·ized, character·iz·ing, character·iz·es 1. To describe the qualities or peculiarities of: characterized the warden as ruthless. 2. by significant progression. 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Benefits and harms of doxycycline doxycycline /doxy·cy·cline/ (dok?se-si´klen) a semisynthetic broad-spectrum tetracycline antibiotic, active against a wide range of gram-positive and gram-negative organisms; used also as d. calcium and d. hyclate. treatment for Gulf War veterans illnesses. Ann Intern intern /in·tern/ (in´tern) a medical graduate serving in a hospital preparatory to being licensed to practice medicine. in·tern or in·terne n. Med 141:85-94. Eisen SA, Kang HK, Murphy FM, Blanchard MS, Reda DJ, Henderson WG, et al. 2005. Gulf War veterans' health: medical evaluation of a US cohort. Ann Intern Med 142:881-890. Fiedler N, Ozakinci G, Hallman W, Wartenberg D, Brewer NT, Barrett DH, et al. 2006. Military deployment Military deployment is the movement of armed forces and their logistical support infrastructure. In most of the world's navies, a deployment designates an extended period of duty at sea. to the Gulf War as a risk factor for psychiatric illness among US troops. Br J Psychiatry psychiatry (səkī`ətrē, sī–), branch of medicine that concerns the diagnosis and treatment of mental, emotional, and behavioral disorders, including major depression, schizophrenia, and anxiety. 188:453-459. Fukuda K, Nisenbaum R, Stewart G, Thompson WW, Robin L, Washko RM, et al. 1998. Chronic multisymptom illness affecting Air Force veterans of the Gulf War. JAMA JAMA abbr. Journal of the American Medical Association 280:981-988. Hallman WK, Kipen HM, Diefenbach M, Boyd K, Kang H, Leventhal H, et al. 2003. Symptom patterns among Gulf War Registry veterans. Am J Public Health 93(4):624-630. Hodgson MJ, Kipen H. 1999. Gulf War illnesses: causation causation Relation that holds between two temporally simultaneous or successive events when the first event (the cause) brings about the other (the effect). According to David Hume, when we say of two types of object or event that “X causes Y” (e.g. and treatment. J Occup Environ Med 41:443-452. Hotopf M, David A, Hull L, Nikalaou V, Unwin C, Wessely S. 2003. Gulf War illness--better, worse, or just the same? A cohort study A cohort study is a form of longitudinal study used in medicine and social science. It is one type of study design. In medicine, it is usually undertaken to obtain evidence to try to refute the existence of a suspected association between cause and disease; failure to refute . BMJ BMJ n abbr (= British Medical Journal) → vom BMA herausgegebene Zeitschrift 327:1370. Hotopf M, David A, Hull L, Nikalaou V, Unwin C, Wessely S. 2004. Risk factors for continued illness among Gulf War veterans: a cohort study. Psychol Med 34:747-754. Iowa Persian Gulf Study Group. 1997. Self-reported illness and health status among Gulf War veterans. A populationbased study. JAMA 277:238-245. Kipen H, Hallman W, Kang HK, Fiedler N, Natelson BH. 1999. Prevalence of chronic fatigue and chemical sensitivities in Gulf Registry veterans. Arch Environ Health 54:313-318. Lashof JC, Cassells JS. 1998. Illness among Gulf War veterans: risk factors, realities, and future research. JAMA 280:1010-1011. Nelson JJ, Natelson BH, Peckerman A, Pollet C, Lange G, Tiersky L, et al. 2001. Medical follow-up of Persian Gulf War Persian Gulf War or Gulf War (1990–91) International conflict triggered by Iraq's invasion of Kuwait in August 1990. Though justified by Iraqi leader Saddam Hussein on grounds that Kuwait was historically part of Iraq, the invasion was presumed to be veterans with severe medically unexplained fatigue: a preliminary study. Mil Med 166:1107-1109. Peckerman A, Natelson BH, Kipen H, Smith SL, Dahl dahl n. 1. See pigeon pea. 2. or dal A thick creamy East Indian stew made with lentils or other legumes, onions, and various spices. K, Pollet C, et al. 1999. Quantitive Quan´ti`tive a. 1. Estimable according to quantity; quantitative. sensory sensory /sen·so·ry/ (sen´sor-e) pertaining to sensation. sen·so·ry adj. 1. Of or relating to the senses or sensation. 2. testing in Gulf War veterans with chronic fatigue syndrome. J Environ Med 1:235-240. Persian Gulf Veterans Coordinating Board. 1995. Unexplained illnesses among Desert Storm veterans. Arch Intern Med 155:262-268. Pollet C, Natelson BH, Lange G, Tiersky L, DeLuca J, Policastro T, et al. 1998. Medical evaluation of Persian Gulf veterans with fatigue and/or chemical sensitivity. J Med 29:101-113. Stuart JA, Murray KM, Ursano RJ, Wright KM. 2002. The Department of Defense's Persian Gulf War Registry year 2000: an examination of veterans' health status. Mil Med 167:121-128. Unwin C, Blatchley N, Coker W, Ferry S, Hotopf M, Hull L, et al. 1999. Health of UK servicemen who served in Persian Gulf War. Lancet lancet /lan·cet/ (lan´set) a small, pointed, two-edged surgical knife. lan·cet n. 353:169-178. Wessely S. 2004. The long aftermath for the 1991 Gulf War. Ann Intern Med 141:155-156. Gozde Ozakinci, (1) William K. Hallman, (2) and Howard M. Kipen (3) (1) Bute Medical School The Bute Medical School is the school of medicine at the University of St Andrews in St Andrews, Fife, Scotland. History The early medical school Medicine was the third subject to be taught at St Andrews, at St Salvator's College and later the United College of , University of St. Andrews, St. Andrews, Fife, Scotland, United Kingdom; (2) Food Policy Institute, Cook College, Rutgers University Rutgers University, main campus at New Brunswick, N.J.; land-grant and state supported; coeducational except for Douglass College; chartered 1766 as Queen's College, opened 1771. Campuses and Facilities Rutgers maintains three campuses. , New Brunswick, New Jersey This article is about the city in New Jersey. For the Canadian province, see New Brunswick. New Brunswick, also known as "the Healthcare City"[2] or "Hub City",[3] is a city and the county seat of the County of Middlesex, New Jersey, USA. , USA; (3) UMDNJ-Robert Wood Johnson Medical School, EOHSI-Clinical Research and Occupational Medicine Division, Piscataway, New Jersey, USA Address correspondence to H.M. Kipen, EOHSI-Clinical Research and Occupational Medicine Division, 170 Frelinghuysen Rd., Room 208, Piscataway, NJ 08854 USA. Telephone: (732) 445-0123, ext 629. Fax: (732) 445-3644. E-mail: kipen@eohsi.rutgers.edu Support was provided by Centers for Disease Control and Prevention Centers for Disease Control and Prevention (CDC), agency of the U.S. Public Health Service since 1973, with headquarters in Atlanta; it was established in 1946 as the Communicable Disease Center. Cooperative Agreement U50/CCU214463-02, the New Jersey Center for Environmental Hazards 'Environmental hazard' is a generic term for any situation or state of events which poses a threat to the surrounding environment. This term incorporates topics like pollution and Natural Hazards such as storms and earthquakes. Research, and National Institute of Environmental Health Sciences The National Institute of Environmental Health Sciences (NIEHS) is one of 27 Institutes and Centers of the National Institutes of Health (NIH),which is a component of the Department of Health and Human Services (DHHS). The Director of the NIEHS is Dr. David A. Schwartz. Center grant ES05022. The authors declare they have no competing financial interests. Received 7 April 2006; accepted 5 July 2006.
Table 1. Severity (mean [+ or -] SD) of 48 symptoms at time 1 and time 2
for highly symptomatic and mildly symptomatic clusters and overall
means.
Mild
Time 1 Time 2
Symptom (n = 242) (n = 242)
Headaches 0.85 [+ or -] 0.98 0.85 [+ or -] 0.97
Eyes or vision 0.51 [+ or -] 0.79 0.67 [+ or -] 0.83
Ears or hearing 0.55 [+ or -] 0.83 0.69 [+ or -] 0.89
Nose or sinuses 0.86 [+ or -] 1.02 0.94 [+ or -] 1.01
Multiple chemical sensitivities 0.39 [+ or -] 0.74 0.51 [+ or -] 0.86
Mouth, teeth, and gums 0.41 [+ or -] 0.75 0.50 [+ or -] 0.83
Ability to taste 0.06 [+ or -] 0.26 0.12 [+ or -] 0.39
Difficulty swallowing 0.11 [+ or -] 0.41 0.21 [+ or -] 0.56
Throat problems 0.22 [+ or -] 0.55 0.26 [+ or -] 0.64
Swollen glands 0.18 [+ or -] 0.46 0.25 [+ or -] 0.58
Difficulty breathing 0.33 [+ or -] 0.66 0.36 [+ or -] 0.69
Coughing 0.38 [+ or -] 0.65 0.46 [+ or -] 0.74
Chest discomfort 0.43 [+ or -] 0.74 0.48 [+ or -] 0.75
Irregular heartbeat 0.16 [+ or -] 0.52 0.29 [+ or -] 0.62
Arms, hands, and shoulders 0.55 [+ or -] 0.87 0.67 [+ or -] 0.87
Back problems 0.70 [+ or -] 0.90 0.86 [+ or -] 0.98
Nausea 0.18 [+ or -] 0.45 0.21 [+ or -] 0.56
Vomiting 0.05 [+ or -] 0.25 0.09 [+ or -] 0.40
Stomach or digestive problems 0.52 [+ or -] 0.86 0.69 [+ or -] 0.93
Diarrhea 0.39 [+ or -] 0.73 0.48 [+ or -] 0.80
Constipation 0.17 [+ or -] 0.51 0.24 [+ or -] 0.57
Abdominal gas 0.54 [+ or -] 0.81 0.72 [+ or -] 0.95*
Abdominal pain 0.29 [+ or -] 0.66 0.42 [+ or -] 0.74
Frequent or painful urination 0.16 [+ or -] 0.46 0.24 [+ or -] 0.66
Muscle aches or cramps 0.57 [+ or -] 0.81 0.82 [+ or -] 0.93*
Sexual or genital problems 0.21 [+ or -] 0.52 0.28 [+ or -] 0.67
Numbness or tingling 0.47 [+ or -] 0.73 0.70 [+ or -] 0.86*
Pain in arms and legs 0.57 [+ or -] 0.82 0.79 [+ or -] 0.95*
Pain in more than one joint 0.71 [+ or -] 0.92 0.86 [+ or -] 0.99
Skin (including rashes) 0.74 [+ or -] 0.95 0.68 [+ or -] 0.98
Hair problems 0.18 [+ or -] 0.51 0.21 [+ or -] 0.61
Cuts or sores 0.34 [+ or -] 0.66 0.33 [+ or -] 0.70
Fainting spells 0.05 [+ or -] 0.26 0.06 [+ or -] 0.29
Losing balance/dizziness 0.38 [+ or -] 0.64 0.52 [+ or -] 0.77
Difficulty concentrating 0.62 [+ or -] 0.81 0.81 [+ or -] 0.89*
Difficulty remembering 0.81 [+ or -] 0.90 1.04 [+ or -] 0.94
Feeling sickly 0.31 [+ or -] 0.59 0.42 [+ or -] 0.74
Unrefreshing sleep 1.01 [+ or -] 0.95 1.14 [+ or -] 0.97
Sleeping more than usual 0.54 [+ or -] 0.82 0.54 [+ or -] 0.86
Fatigue (not from exercise) 0.92 [+ or -] 0.87 1.04 [+ or -] 0.98
Fatigue after exercise 0.37 [+ or -] 0.71 0.55 [+ or -] 0.86
Unexplained weakness 0.39 [+ or -] 0.64 0.48 [+ or -] 0.79
Feeling anxious 0.61 [+ or -] 0.76 0.71 [+ or -] 0.91
Sudden mood changes 0.64 [+ or -] 0.81 0.72 [+ or -] 0.90
Sensitivity to heat or cold 0.37 [+ or -] 0.71 0.44 [+ or -] 0.80
Fever or chills 0.14 [+ or -] 0.42 0.19 [+ or -] 0.52
Sweating 0.31 [+ or -] 0.73 0.48 [+ or -] 0.84
Feeling depressed or blue 0.59 [+ or -] 0.80 0.71 [+ or -] 0.98
High
Time 1 Time 2
Symptom (n = 148) (n = 148)
Headaches 2.11 [+ or -] 0.91 1.77 [+ or -] 0.98*
Eyes or vision 1.36 [+ or -] 0.94 1.45 [+ or -] 0.94
Ears or hearing 1.37 [+ or -] 1.05 1.30 [+ or -] 1.01
Nose or sinuses 1.86 [+ or -] 1.07 1.74 [+ or -] 1.11
Multiple chemical sensitivities 1.51 [+ or -] 1.12 1.57 [+ or -] 1.17
Mouth, teeth, and gums 1.25 [+ or -] 1.11 1.22 [+ or -] 1.08
Ability to taste 0.69 [+ or -] 0.90 0.70 [+ or -] 0.89
Difficulty swallowing 0.72 [+ or -] 0.85 0.73 [+ or -] 0.93
Throat problems 1.03 [+ or -] 1.04 0.84 [+ or -] 0.94
Swollen glands 1.01 [+ or -] 1.05 0.79 [+ or -] 0.94
Difficulty breathing 1.45 [+ or -] 1.00 1.03 [+ or -] 0.95*
Coughing 1.39 [+ or -] 1.07 1.21 [+ or -] 1.06
Chest discomfort 1.56 [+ or -] 0.94 1.33 [+ or -] 1.01
Irregular heartbeat 0.71 [+ or -] 1.03 0.71 [+ or -] 0.91
Arms, hands, and shoulders 1.82 [+ or -] 1.08 1.63 [+ or -] 1.03
Back problems 1.78 [+ or -] 1.01 1.75 [+ or -] 1.11
Nausea 0.99 [+ or -] 0.95 0.84 [+ or -] 0.93
Vomiting 0.47 [+ or -] 0.77 0.39 [+ or -] 0.73
Stomach or digestive problems 1.59 [+ or -] 1.07 1.53 [+ or -] 1.08
Diarrhea 1.29 [+ or -] 1.08 1.21 [+ or -] 1.08
Constipation 0.61 [+ or -] 0.85 0.74 [+ or -] 0.95
Abdominal gas 1.74 [+ or -] 1.05 1.54 [+ or -] 1.10
Abdominal pain 1.41 [+ or -] 0.98 1.26 [+ or -] 1.04
Frequent or painful urination 0.74 [+ or -] 0.95 0.69 [+ or -] 0.90
Muscle aches or cramps 1.95 [+ or -] 0.86 1.81 [+ or -] 1.06
Sexual or genital problems 0.97 [+ or -] 1.12 0.93 [+ or -] 1.10
Numbness or tingling 1.80 [+ or -] 0.89 1.72 [+ or -] 1.08
Pain in arms and legs 2.11 [+ or -] 0.87 1.88 [+ or -] 1.06
Pain in more than one joint 2.17 [+ or -] 0.88 2.05 [+ or -] 1.00
Skin (including rashes) 1.69 [+ or -] 1.12 1.37 [+ or -] 1.15
Hair problems 0.81 [+ or -] 1.03 0.72 [+ or -] 1.00
Cuts or sores 1.04 [+ or -] 1.06 0.91 [+ or -] 1.06
Fainting spells 0.32 [+ or -] 0.73 0.24 [+ or -] 0.56
Losing balance/dizziness 1.43 [+ or -] 1.04 1.27 [+ or -] 0.93
Difficulty concentrating 1.99 [+ or -] 0.90 1.87 [+ or -] 0.91
Difficulty remembering 2.13 [+ or -] 0.88 2.11 [+ or -] 0.94
Feeling sickly 1.59 [+ or -] 0.98 1.37 [+ or -] 0.99
Unrefreshing sleep 2.48 [+ or -] 0.73 2.26 [+ or -] 0.83*
Sleeping more than usual 1.62 [+ or -] 1.21 1.28 [+ or -] 1.20*
Fatigue (not from exercise) 2.34 [+ or -] 0.81 2.18 [+ or -] 0.81
Fatigue after exercise 1.82 [+ or -] 1.06 1.74 [+ or -] 1.13
Unexplained weakness 1.91 [+ or -] 0.98 1.72 [+ or -] 1.04
Feeling anxious 2.00 [+ or -] 0.95 1.74 [+ or -] 1.01
Sudden mood changes 2.11 [+ or -] 1.02 1.80 [+ or -] 1.07*
Sensitivity to heat or cold 1.49 [+ or -] 1.18 1.34 [+ or -] 1.18
Fever or chills 1.09 [+ or -] 1.05 0.84 [+ or -] 0.92
Sweating 1.39 [+ or -] 1.10 1.28 [+ or -] 1.11
Feeling depressed or blue 1.95 [+ or -] 1.00 1.61 [+ or -] 1.09*
Overall mean
Symptom Time 1/time 2
Headaches 1.33/1.20
Eyes or vision 0.83/0.96
Ears or hearing 0.86/0.93
Nose or sinuses 1.24/1.25
Multiple chemical sensitivities 0.81/0.92
Mouth, teeth, and gums 0.73/0.77
Ability to taste 0.30/0.34
Difficulty swallowing 0.34/0.41
Throat problems 0.53/0.48
Swollen glands 0.49/0.46
Difficulty breathing 0.75/0.62
Coughing 0.76/0.74
Chest discomfort 0.86/0.80
Irregular heartbeat 0.37/0.45
Arms, hands, and shoulders 1.03/1.03
Back problems 1.11/1.20
Nausea 0.49/0.45
Vomiting 0.21/0.20
Stomach or digestive problems 0.93/1.01
Diarrhea 0.73/0.76
Constipation 0.33/0.43
Abdominal gas 0.99/1.03
Abdominal pain 0.72/0.74
Frequent or painful urination 0.38/0.41
Muscle aches or cramps 1.09/1.19
Sexual or genital problems 0.50/0.53
Numbness or tingling 0.97/1.08
Pain in arms and legs 1.15/1.20
Pain in more than one joint 1.27/1.31
Skin (including rashes) 1.10/0.94
Hair problems 0.42/0.40
Cuts or sores 0.61/0.55
Fainting spells 0.15/0.13
Losing balance/dizziness 0.78/0.80
Difficulty concentrating 1.14/1.21
Difficulty remembering 1.31/1.45
Feeling sickly 0.80/0.78
Unrefreshing sleep 1.57/1.57
Sleeping more than usual 0.95/0.82
Fatigue (not from exercise) 1.46/1.47
Fatigue after exercise 0.92/1.00
Unexplained weakness 0.96/0.95
Feeling anxious 1.14/1.10
Sudden mood changes 1.20/1.13
Sensitivity to heat or cold 0.79/0.78
Fever or chills 0.50/0.44
Sweating 0.72/0.79
Feeling depressed or blue 1.11/1.05
*Significantly different from time 1 to time 2 within highly symptomatic
and mildly symptomatic clusters.
Table 2. Demographic characteristics of the sample (n = 390).
Demographic variable No. (%)
Sex
Male 364 (93.3)
Female 26 (6.7)
Military branch
Army 267 (68.5)
Air Force 35 (9.0)
Marines 64 (16.4)
Navy 24 (6.2)
Education
High school 108 (27.7)
College 231 (59.2)
Graduate school 51 (13.1)
Duty
Active duty 227 (58.2)
National Guard 72 (18.5)
Reserves 91 (23.3)
Race
White 324 (83.1)
Black 66 (16.9)
Martial status
Married 217 (55.6)
Divorced 19 (4.9)
Separated 13 (3.3)
Single, never married 132 (33.8)
Not married but living with mate 9 (2.3)
Rank
Enlisted 183 (46.9)
NCO 157 (40.3)
Warrant officer 8 (2.1)
Commissioned officer 42 (10.8)
Smoker
Never smoked 178 (45.6)
Former smoker 111 (28.5)
Current smoker 101 (25.9)
Table 3. Number of symptoms (mean [+ or -] SD) at time 1 and time 2
across demographic variables and cluster membership.
Demographic variable Time 1 Time 2
Cluster membership
Mildly symptomatic 14.22 [+ or -] 8.67 16.55 [+ or -] 10.49
Highly symptomatic 34.90 [+ or -] 7.15 32.86 [+ or -] 9.64
Sex
Male 22.02 [+ or -] 12.96 22.81 [+ or -] 12.96
Female 22.73 [+ or -] 12.57 22.81 [+ or -] 12.03
Military branch
Army 23.47 [+ or -] 12.46 24.14 [+ or -] 12.76
Air Force 23.60 [+ or -] 12.39 23.66 [+ or -] 12.09
Marines 16.72 [+ or -] 13.86 18.14 [+ or -] 13.44
Navy 18.54 [+ or -] 12.44 18.13 [+ or -] 10.55
Education
High school 23.62 [+ or -] 13.12 24.31 [+ or -] 12.79
college 22.45 [+ or -] 12.95 23.42 [+ or -] 13.01
Graducate school 17.04 [+ or -] 11.24 16.33 [+ or -] 10.65
Duty
Active duty 22.77 [+ or -] 13.22 23.26 [+ or -] 12.93
National Guard 21.42 [+ or -] 11.78 23.04 [+ or -] 11.93
Reserves 20.83 [+ or -] 13.01 21.20 [+ or -] 13.50
Race
White 21.47 [+ or -] 12.68 21.41 [+ or -] 12.45
Black 25.00 [+ or -] 13.77 29.26 [+ or -] 13.12
Marital status
Married 22.77 [+ or -] 13.18 23.75 [+ or -] 13.17
Divorced 25.53 [+ or 0] 13.79 25.26 [+ or -] 13.77
Separated 21.00 [+ or -] 13.48 23.62 [+ or -] 13.74
Single, never married 20.64 [+ or -] 12.26 20.40 [+ or -] 12.14
Not married but 20.22 [+ or -] 13.34 26.11 [+ or -] 11.21
living with mate
Rank
Enlisted 21.54 [+ or -] 12.99 21.71 [+ or -] 12.69
NCO 23.85 [+ or -] 12.82 25.50 [+ or -] 13.14
Warrant officer 19.13 [+ or -] 16.14 22.25 [+ or -] 13.81
Full officer 18.29 [+ or -] 11.56 17.00 [+ or -] 10.16
Smoker
Never smoked 20.92 [+ or -] 13.15 20.87 [+ or -] 13.12
Former smoker 21.24 [+ or -] 13.17 23.19 [+ or -] 12.69
Current smoker 25.00 [+ or -] 11.85 25.54 [+ or -] 12.25
Table 4. Significant main and interaction effects (except the main
effect of cluster membership) for change in symptom severity.
Source F (1, 379) p-Value
Age
Arms, hands, shoulders 21.29 0.000
Back problems 11.64 0.001
Frequent or painful urination 11.88 0.001
Sexual or genital problems 22.07 0.000
Pain in arms or legs 12.28 0.001
Pain in more than one joint 13.60 0.000
Race
Constipation 13.98 0.000
Hair 11.05 0.001
Sweating not due to exercise 10.70 0.001
Time x smoker status
Mouth, teeth, gums 11.29 0.001
Time x cluster membership
Headaches 12.45 0.000
Swollen glands in neck or armpit 10.81 0.001
Difficulty breathing 23.69 0.000
Abdominal gas 15.72 0.000
Abdominal pain 10.68 0.001
Muscle aches or cramps 18.20 0.000
Numbness or tingling sensations 11.52 0.001
Pain in arms or legs 21.78 0.000
Difficulty concentrating 10.85 0.001
Feeling sickly 14.40 0.000
Unrefreshing sleep 13.84 0.000
Sleeping more than usual 12.58 0.000
Unexplained weakness 13.19 0.000
Feeling anxious or upset 16.49 0.000
Sudden mood changes 20.62 0.000
Fever or chills 15.61 0.000
Sweating not due to exercise 12.14 0.001
Feeling depressed or blue 22.87 0.000
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