Report of the Institute of Medicine Committee on the Efficacy and Safety of Halcion.
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Adverse Drug Reaction Reporting Systems↗
Biomedical subjects
P D Stolley
Publications and source records attributed to P D Stolley.
Elevated tissue plasminogen activator antigen and stroke risk: The Stroke Prevention In Young Women Study.
BACKGROUND AND PURPOSE: Abnormalities in endogenous fibrinolysis are associated with an increased risk for stroke in men and older adults. We tested the hypothesis that elevated plasma tissue plasminogen activator (tPA) antigen, a marker for impaired endogenous fibrinolysis, is an independent risk factor for stroke in young women. METHODS: Subjects were 59 nondiabetic females ages 15 to 44 years with cerebral infarction from the Baltimore-Washington area and 97 control subjects frequency-matched for age who were recruited by random-digit dialing from the same geographic area. A history of cerebrovascular disease risk factors was obtained by face-to-face interview. Plasma tPA antigen was measured by enzyme-linked immunosorbent assay. RESULTS: Mean plasma tPA antigen levels were significantly higher in stroke patients than control subjects (4. 80+/-4.18 versus 3.23+/-3.67 ng/mL; P=0.015). After adjustment for age, hypertension, cigarette smoking, body mass index, and ischemic heart disease, there was a dose-response association between tPA antigen and stroke with a 3.9-fold odds ratio of stroke (95% CI, 1.2 to 12.4; P=0.03) for the upper quartile (>4.9 ng/mL) of tPA antigen compared with the lowest quartile. The dose-response relationship between tPA antigen and stroke was equally present in white and nonwhite women, and further adjustment for total and HDL cholesterol levels only modestly attenuated this association. CONCLUSIONS: This population-based case-control study shows that elevated plasma tPA antigen level is independently associated with an increased risk for ischemic stroke in nondiabetic females 15 to 44 years of age. These findings support the hypothesis that impaired endogenous fibrinolysis is an important risk factor for stroke in young women.
Adolescent↗
The Guillain-Barré syndrome and the 1992-1993 and 1993-1994 influenza vaccines.
BACKGROUND: The number of reports of influenza-vaccine-associated Guillain-Barré syndrome to the national Vaccine Adverse Event Reporting System increased from 37 in 1992-1993 to 74 in 1993-1994, arousing concern about a possible increase in vaccine-associated risk. METHODS: Patients given a diagnosis of the Guillain-Barré syndrome in the 1992-1993 and 1993-1994 influenza-vaccination seasons were identified in the hospital-discharge data bases of four states. Vaccination histories were obtained by telephone interviews during 1995-1996 and were confirmed by the vaccine providers. Disease with an onset within six weeks after vaccination was defined as vaccine-associated. Vaccine coverage in the population was measured through a random-digit-dialing telephone survey. RESULTS: We interviewed 180 of 273 adults with the Guillain-Barré syndrome; 15 declined to participate, and the remaining 78 could not be contacted. The vaccine providers confirmed influenza vaccination in the six weeks before the onset of Guillain-Barré syndrome for 19 patients. The relative risk of the Guillain-Barré syndrome associated with vaccination, adjusted for age, sex, and vaccine season, was 1.7 (95 percent confidence interval, 1.0 to 2.8; P=0.04). The adjusted relative risks were 2.0 for the 1992-1993 season (95 percent confidence interval, 1.0 to 4.3) and 1.5 for the 1993-1994 season (95 percent confidence interval, 0.8 to 2.9). In 9 of the 19 vaccine-associated cases, the onset was in the second week after vaccination, all between day 9 and day 12. CONCLUSIONS: There was no increase in the risk of vaccine-associated Guillain-Barré syndrome from 1992-1993 to 1993-1994. For the two seasons combined, the adjusted relative risk of 1.7 suggests slightly more than one additional case of Guillain-Barré syndrome per million persons vaccinated against influenza.
Adolescent↗
Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study.
BACKGROUND: Although antibiotic prophylaxis against infective endocarditis is recommended, the true risk factors for infective endocarditis are unclear. OBJECTIVE: To quantitate the risk for endocarditis from dental treatment and cardiac abnormalities. DESIGN: Population-based, case-control study. SETTING: 54 hospitals in the Philadelphia area. PATIENTS: Persons with community-acquired infective endocarditis not associated with intravenous drug use were compared with community residents, matched by age, sex, and neighborhood of residence. MEASUREMENTS: Information on demographic characteristics, host risk factors, and dental treatment was obtained from structured telephone interviews, dental records, and medical records. RESULTS: During the preceding 3 months, dental treatment was no more frequent among case-patients than controls (adjusted odds ratio, 0.8 [95% CI, 0.4 to 1.5]). Of 273 case-patients, 104 (38%) knew of previous cardiac lesions compared with 17 controls (6%) (adjusted odds ratio, 16.7 [CI, 7.4 to 37.4]). Case-patients more often had a history of mitral valve prolapse (adjusted odds ratio, 19.4 [CI, 6.4 to 58.4]), congenital heart disease (adjusted odds ratio, 6.7 [CI, 2.3 to 19.4]), cardiac valvular surgery (adjusted odds ratio, 74.6 [CI, 12.5 to 447]), rheumatic fever (adjusted odds ratio, 13.4 [CI, 4.5 to 39.5]), and heart murmur without other known cardiac abnormalities (adjusted odds ratio, 4.2 [CI, 2.0 to 8.9]). Among case-patients with known cardiac lesions--the target of prophylaxis--dental therapy was significantly (P = 0.03) less common than among controls (adjusted odds ratio, 0.2 [CI, 0.04 to 0.7] over 3 months). Few participants received prophylactic antibiotics. CONCLUSIONS: Dental treatment does not seem to be a risk factor for infective endocarditis, even in patients with valvular abnormalities, but cardiac valvular abnormalities are strong risk factors. Few cases of infective endocarditis would be preventable with antibiotic prophylaxis, even with 100% effectiveness assumed. Current policies for prophylaxis should be reconsidered.
Adolescent↗
Calcium channel blockers and the risk of cancer.
CONTEXT: Recent epidemiologic studies have raised the concern that calcium channel blocker use may increase the risk of cancer overall and of several specific cancers. OBJECTIVE: To assess whether calcium channel blocker use increases the risk of cancer overall and of specific cancers. DESIGN: Case-control drug surveillance study based on data collected from 1983 to 1996. SETTING: Hospitals in Baltimore, Md, New York, NY, and Philadelphia, Pa. PATIENTS: A total of 9513 patients aged 40 to 69 years with incident cancer of various sites and 6492 controls aged 40 to 69 years admitted for nonmalignant conditions. MAIN OUTCOME MEASURES: Incident cancer overall and 23 specific cancers. RESULTS: Calcium channel blocker use was unrelated to the risk of cancer overall (relative risk [RR], 1.1; 95% confidence interval [CI], 0.9-1.3). Use was not significantly associated with increased risks of individual cancers, including those previously implicated, except cancer of the kidney (RR, 1.8; 95% CI, 1.1 -2.7). Recent use, use for 5 or more years, and use of individual calcium channel blocker drugs were also not associated with cancer incidence. Use of beta-blockers and angiotensin-converting enzyme inhibitors was generally unrelated to cancer overall or individual cancers, but both were associated with kidney cancer (RR, 1.8; 95% CI, 1.3-2.5; and RR, 1.9; 95% CI, 1.2-3.0, respectively). CONCLUSIONS: The present study suggests that the use of calcium channel blockers is unrelated to an increase in the overall risk of cancer or of individual cancers, except kidney cancer, which has been associated with hypertension or drugs to treat hypertension in previous studies.
Adult↗
Growth of hypercholesterolemic children completing physician-initiated low-fat dietary intervention.
OBJECTIVE: To evaluate the growth of hypercholesterolemic children completing an innovative, physician-initiated, home-based nutrition education program or standard nutrition counseling that aims to lower dietary fat intake. STUDY DESIGN: From suburban pediatric practices, 261 3.9- to 9.9-year-old children with elevated cholesterol levels and 81 children with nonelevated cholesterol levels were identified. The children with hypercholesterolemia were randomly assigned to the home-based education program, standard nutrition counseling, or an at-risk control group. Height, weight, skinfold measures, and dietary intake were evaluated at baseline, 3, 6, and 12 months; changes in anthropometric measures among treatment groups were compared over time. RESULTS: The intervention groups demonstrated significant decreases in fat and saturated fat intake after the interventions; however, weight z-score, height z-weight-for-height-median, and sum of skinfolds did not vary among the treatment groups over the year. At baseline, height z-score, weight z-score, and weight-for-height-median were positively associated with caloric intake, whereas weight z-score, weight-for-height-median, and sum of skinfolds were positively associated with fat intake. When the groups were combined and the children were grouped by average fat intake quintiles, no association between fat intake and changes in weight z-score, height z-score, or weight-for-height-media was observed. Differences over time in sum of skinfolds among fat intake quintile groups (suggesting a negative association between fat intake and body fat) that approached statistical significance (p = 0.06) were observed. CONCLUSIONS: These results support the safety, with respect to growth, of physician-initiated dietary intervention and lower fat diets for children with hypercholesterolemia. In addition, low dietary fat intake was associated with lower body fat.
Body Height↗
Transitional cell cancer of the urinary tract and renal cell cancer in relation to acetaminophen use (United States).
Experimental and epidemiologic evidence have suggested that phenacetin use increases the risk of transitional cell cancers of the urinary tract. The drug is no longer marketed but a commonly used metabolite, acetaminophen, has been linked recently to an increased risk of renal cancer. We assessed the relation of acetaminophen use to the risk of transitional cell cancer of the urinary tract and of renal cell cancer with data from a hospital-based study of cancers and medication use conducted from 1976-96 in the eastern United States. We compared 498 cases of transitional cell cancer and 383 cases of renal cell cancer with 8,149 noncancer controls and 6,499 cancer controls and controlled confounding factors with logistic regression. For transitional cell cancer, the relative risk (RR) estimate for regular acetaminophen use that had begun at least a year before admission was 1.1 (95 percent confidence interval [CI] = 0.6-1.9) based on noncancer controls, and 0.9 (CI = 0.5-1.6) based on cancer controls. RR estimates for use that lasted at least five years, and for nonregular use, were also close to 1.0. For renal cell cancer, the corresponding estimates were again close to 1.0. Our results suggest that acetaminophen, as used in present study population, does not influence the risk of transitional cell cancer of the urinary tract or of renal cell cancer.
Acetaminophen↗
Platelet glycoprotein receptor IIIa polymorphism P1A2 and ischemic stroke risk: the Stroke Prevention in Young Women Study.
BACKGROUND AND PURPOSE: Platelet glycoprotein IIb/IIa (GpIIb-IIIa), a membrane receptor for fibrinogen and von Willebrand factor, has been implicated in the pathogenesis of acute coronary syndromes but has not been previously investigated in relation to stroke in young adults. METHODS: We used a population-based case-control design to examine the association of the GpIIIa polymorphism P1A2 with stroke in young women. Subjects were 65 cerebral infarction cases (18 patients with and 47 without an identified probable etiology) 15 to 44 years of age from the Baltimore-Washington region and 122 controls frequency matched by age from the same geographic area. A face-to-face interview for vascular disease risk factors and a blood sample for the P1A2 allele and serum cholesterol were obtained from each participant. Logistic regression was used to estimate the odds ratio for one or more P1A2 alleles after adjustment for other risk factors. RESULTS: Among cases and controls, the prevalence rates of one or more P1A2 alleles were 21% and 22% among blacks and 36% and 28% among whites, respectively. This genotype was significantly associated with hypertension only in black control subjects but otherwise not with any of the established vascular risk factors. The adjusted odds ratio for cerebral infarction of one or more P1A2 alleles was 1.1 (confidence interval [CI], 0.6 to 2.3) overall, 0.5 (CI, 0.1 to 7.1) among blacks, and 1.4 (CI, 0.5 to 3.7) among whites. For the cases with an identified probable etiology, the corresponding odds ratios were 3.0 (CI, 0.9 to 10.4) overall, 0.7 (CI, 0.1 to 7.1) among blacks, and 12.8 (CI, 1.2 to 135.0) among whites. CONCLUSIONS: No association was found between the P1A2 polymorphism of GpIIIa and young women with stroke. However, subgroup analyses showed that the P1A2 polymorphism of GpIIIa appeared to be associated with stroke risk among white women, particularly those with a clinically identified probable etiology for their stroke. Further work with an emphasis on stroke subtypes and with multiracial populations is warranted.
Adolescent↗
Thermolabile methylenetetrahydrofolate reductase polymorphism (C677T) and total homocysteine concentration among African-American and white women.
A polymorphism associated with a thermolabile variant (C677T) of the enzyme methylenetetrahydrofolate reductase has been associated with both elevated total homocysteine (tHcy) levels and risk for cardiovascular disease. Data from the Stroke Prevention in Young Women Study were used to determine the prevalence of the C677T genotype and to assess whether environmental factors modified the association between genotype and tHcy concentration. The C677T genotype prevalence was 80% -/-, 20% +/-, and 0% +/+ among 46 African-American women; and 39% -/-, 53% +/-, and 8% +/+ among 77 white women (P < 0.01). There was a trend toward higher tHcy levels in African-American women with the +/- genotype when compared with the -/- genotype (6.9 mumol/L vs 5.3 mumol/L respectively, p = 0.10); no association was found among the white women (6.0 mumol/L, -/-; 4.5 mumol/L, +/-; and 6.2 mumol/L, +/+; p = 0.67). Among African American women, those who smoked and were +/- genotype had the highest tHcy levels (8.0 mumol/L); while among white women, those who smoked and were -/- had the highest tHcy levels (8.1 mumol/L). Despite being hampered by a limited sample size, the thermolabile allele is significantly less common among African-American than white women. The association between genotype and tHcy concentration is influenced by smoking and multivitamin use.
Adolescent↗
Hormone replacement and menopausal symptoms following hysterectomy.
Hormone replacement therapy (HRT) is recommended for most women who experience surgical menopause following hysterectomy/oophorectomy for noncancerous conditions; it is also commonly prescribed for postmenopausal women. Beginning in 1992, 1,299 women undergoing hysterectomy in 28 hospitals throughout Maryland were interviewed prior to hysterectomy and were subsequently followed over a 2-year period. Interviews included questions about HRT use and symptoms associated with menopause. The majority of the women (66 percent) were white, 55 percent had a high school education or better, 49 percent were obese (body mass index > or =27.3), and 11 percent were postmenopausal. Over 40 percent of premenopausal women underwent bilateral oophorectomy. At 3 months posthysterectomy, 89 percent of these women were on HRT; this figure dropped to 85 percent at 24 months. Among postmenopausal women, 50 percent were on HRT both at 3 months and at 24 months posthysterectomy. Among premenopausal women who had unilateral oophorectomy, 21 percent were on HRT at 3 months, increasing to 35 percent at 24 months. Among premenopausal women who had no ovaries removed, 5 percent were on HRT at 3 months, increasing to 13 percent at 24 months. There were few within-group differences between HRT users and nonusers, except that among postmenopausal women, HRT users were younger and more likely to be white and had higher income and educational levels. Women who were postmenopausal or who underwent bilateral oophorectomy were less likely to have hot flashes if they were on HRT, but women with 0-1 ovary removed who were on HRT were more likely to have hot flashes than those not on HRT. Black women were significantly more likely to experience hot flashes than were white women, independent of HRT status and weight. Obese women were on HRT at approximately the same rates as nonobese women but were significantly more likely to have hot flashes, even when analyses controlled for HRT and race.
Adult↗
Induced and spontaneous abortion in relation to risk of breast cancer (United States).
The relation of induced and spontaneous abortion to the risk of breast cancer is evaluated in a hospital-based case-control interview study conducted in three cities in the United States from 1985 through 1995. Cases were 1,803 women aged 25 to 64 years with newly diagnosed invasive breast cancer; controls were 4,182 women of the same ages admitted for conditions unrelated to reproductive factors. Other breast cancer risk-factors were controlled through multiple logistic regression. The reference for all analyses was women who had never had an abortion, either induced or spontaneous. Among parous women, the relative risk (RR) estimate was 1.1 (95 percent confidence interval [CI] = 0.9-1.5) for induced abortion overall, 1.0 (CI = 0.7-1.4) for abortion before the first birth, and 1.3 (CI = 1.0-1.8) for abortion after at least one birth. Among nulliparous women, the relative risk estimate for induced abortion was 1.3 (CI = 0.9-1.9). There was no trend of increased risk with number of abortions, nor was there consistent evidence of an increased risk in any particular subgroup. Spontaneous abortion was not associated with increased risk of breast cancer, either among nulliparous women or among parous women. These findings provide little support for the hypothesis that induced abortion increases breast cancer risk overall or in particular subgroups.
Abortion, Induced↗
Concepts of fever: recent advances and lingering dogma.
Fever has been a preoccupation of clinicians since medicine's beginning. One might therefore expect that basic concepts relating to this physiological response would be well delineated and that such concepts would be widely known. In fact, only in the past several decades has the febrile response been subjected to scientific scrutiny. As a result of recent scientific investigation, modern concepts have evolved from a perception of fever as nothing more than a rise in core temperature to one in which fever is recognized as a complex physiological response characterized by a cytokine-mediated rise in temperature, as well as by generation of acute-phase reactants and activation of a panoply of physiological, endocrinologic, and immunologic systems. The average clinician appears to have little more than a regrettably rudimentary knowledge of these modern concepts of fever. This symposium summary considers many such concepts that have immediate relevance to the practice of medicine.
Acute-Phase Proteins↗
Generations of misplaced confidence. A personal view.
A humorous look at one family's experience with the milestones of medical achievement illustrates the need for continued research on the efficacy of treatment. Skepticism about the benefits of new treatments and careful examination of even standard procedures should be encouraged within the medical profession.
Adult↗
Uterine leiomyomas. Racial differences in severity, symptoms and age at diagnosis.
OBJECTIVE: To investigate racial differences in the presence of leiomyomas, condition severity, associated symptoms and age at diagnosis between black and white hysterectomy patients. STUDY DESIGN: This study included 409 black women and 836 white women aged 18 or older who underwent hysterectomy for noncancerous conditions at 28 hospitals in Maryland. Patients were interviewed shortly before surgery, and hospital records were abstracted after discharge. RESULTS: Overall, 89% of the black women and 59% of the white women were found to have leiomyomas. Among those with a confirmed presurgical diagnosis of leiomyomas, the average age at diagnosis was 37.5 years for black women and 41.6 for white women, and the average age at hysterectomy was 41.7 for black women and 44.6 for white women. The average uterine weight for black women with leiomyomas was 420.8 g and for white women was 319.1 g. Black women were more likely to have seven or more leiomyomas (57%) in comparison to white women (36%). Black women with leiomyomas were more likely to be anemic (56%) than white women (38%) and more likely to report having very severe or severe pelvic pain (59%) than white women (41%). CONCLUSION: Black women having hysterectomy had larger and more numerous leiomyomas, and the leiomyomas were more symptomatic than in white women despite a younger age at diagnosis and hysterectomy.
Adult↗
Cancer incidence in a group of workers potentially exposed to ethylene oxide.
BACKGROUND: Cytogenetic changes associated with ethylene oxide (ETO) exposure at a worksite prompted a study of cancer incidence in that cohort. METHOD: Cancer incidence through 31 December 1987 was ascertained in a cohort of 1132 individuals employed at the worksite at any time from 1 July 1974 through 30 September 1980, the period of potential exposure to ETO at the plant. The number of observed cancers was compared with that expected based on age- and sex-specific incidence rates reported by the National Cancer Institute's Surveillance Epidemiology and End Results Program. Standardized morbidity ratios (SMR) were calculated separately for regular and temporary employees. RESULTS: Of the 28 cancers observed in the cohort, 12 were breast cancers. The SMR for breast cancer among regular female employees ranged from 2.55 (95% CI: 1.31-4.98, P = 0.02) to 1.70 (95% CI: 0.89-3.23, P = 0.09) depending on calendar year of follow-up, assumptions about completeness of follow-up, and the reference rates used. The excess of breast cancer over expected in regular female employees diminished over time. No statistically significant excess of breast cancer was noted for temporary female employees at any point during follow-up. No increase in cancer incidence was found over that expected for any cancer sites associated with ETO in previous studies--leukaemia, brain, pancreas and stomach. CONCLUSIONS: Factors such as appropriateness of latency periods, length of follow-up and lack of a common histopathological type need to be considered in evaluating the excesses in observed breast cancer incidence, which diminished over time.
Adult↗
Nonhormonal drugs and cancer.
Nonhormonal drugs probably account for only a small proportion of human cancer but have contributed many valuable insights into carcinogenic mechanisms. The antineoplastics, radiopharmaceuticals, and a few other agents account for most of the known drug-induced cancer. A number of other agents are under suspicion, usually due to studies in laboratory animals or to preliminary clinical or epidemiologic observations. This group includes some drugs in widespread use such as clofibrate and cimetidine. For a few drugs that are carcinogenic in animals, such as dapsone and isoniazid, epidemiologic studies have shown little to no evidence of carcinogenicity. Recent experimental studies have shown tumor promotion by the commonly used antidepressants amitriptyline and fluoxetine and some antihistamines, which deserve epidemiologic investigation of cancer risk. Some drugs may also protect against cancer, as suggested by the lower risk of colorectal cancer among regular users of nonsteroidal antiinflammatory drugs. Pharmacoepidemiologic studies must take into account possible confounding by the original conditions for which drugs were taken and the typically long latency period of drug-induced cancer. Improved postmarketing surveillance, continued routine case-control surveillance, and ad hoc case-control and cohort studies are needed to evaluate drugs already in use as well as newly introduced agents.
Animals↗
Predictors of lead stores in male veterans.
Thirty-two male veterans participated in a study to determine cumulative lead exposure in an urban population. Subjects were chosen on the basis of blood pressure status in order to attempt to compare lead exposure between patients with and without hypertension. Patients currently enrolled in hypertension clinic and on treatment were recruited and matched with controls for age, race, and socioeconomic status. Each subject underwent provocative chelation via slow intravenous infusion of CaNa2 EDTA and 6-h urinary lead measurement and completed an interviewer-administered questionnaire. Twenty blacks and 12 whites participated, with a median age of 52 years (range: 27 to 72). Urinary lead excretion ranged from below detection limits to frankly toxic levels in an individual with heavy moonshine ingestion. Lead levels were higher than reported in other non-workplace populations. The distribution of lead values was skewed, as expected, with a median excretion of 75 mcg lead/6 h (corresponding to a median 24 degrees post-chelation urinary lead excretion of 286 mcg) and modal values between 50 and 75 micrograms lead. Levels of 95 mcg lead/6 h (corresponding to 24 degrees levels of 333 mcg lead) and above were considered "high" (N = 11) and the remainder were "low" (N = 21). Among those able to recall various characteristics of their first childhood dwellings, the presence of flaking paint in a multiple family dwelling was strongly associated with "high" lead excretion (X2 = 9.32, p = 0.009). Hypertensives excreted slightly more lead than nonhypertensives, although the difference was not statistically significant in this small sample. Lead excretion was not associated with current (treated) blood pressure determinations among hypertensives. However, lead excretion was associated with systolic pressure as recorded on entry to the hypertension clinic (N = 21, R2 = 0.24, p = 0.03).
Adult↗
Shingles, allergies, family medical history, oral contraceptives, and other potential risk factors for systemic lupus erythematosus.
The authors undertook a case-control study to explore the many factors that have been postulated to be related to the etiology of systemic lupus erythematosus. A total of 195 cases of systemic lupus diagnosed in the Philadelphia, Pennsylvania, metropolitan area between 1985 and 1987 were compared with 143 controls, friends of the cases matched to them according to age (+/- 5 years) and sex. Through personal interviews and chart reviews, data were collected on demographic factors, personal and familial medical history, reproductive history, medication history, and environmental exposures. Associations were found between systemic lupus erythematosus and having a family history of autoimmune disease (age-, sex-, and race-adjusted odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.2-4.6), a history of shingles (adjusted OR = 6.4, 95% CI 1.4-28.0), a history of hives (adjusted OR = 1.8, 95% CI 1.1-3.0), and a history of medication allergies (adjusted OR = 2.6, 95% CI 1.5-4.5). No association was present between systemic lupus erythematosus and either any use or recent use of oral contraceptives (e.g., OR = 0.6 (95% CI 0.2-1.4) for use in the 3 years prior to diagnosis), family history of multiple other diseases, or a history of numerous other infections or various other types of allergies. Thus, these data indicate that systemic lupus erythematosus is associated with a family history of autoimmune diseases, a history of shingles, and a history of allergies. In contrast, if the development of systemic lupus is affected by use of oral contraceptives, this effect must be extremely modest. These findings may help clarify the possible pathogenesis of systemic lupus erythematosus, and they provide clues as to when the presence of systemic lupus should be suspected.
Adult↗