Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock.

Plasma endotoxin and lipopolysaccharide-binding protein (LBP) levels were measured in a group of 253 patients at the onset of severe sepsis and/or septic shock. Endotoxin levels were significantly greater than control levels (n=33; mean +/- SD, 5.1+/-7.3 pg/mL) in 78.3% of patients. Median endotoxin levels in patients with sepsis were 300 pg/mL (25%-75% interquartile range, 110-726 pg/mL). LBP levels were elevated in 97% of patients compared with normal control values of 4.1+/-1.65 microgram/mL. Median LBP levels in patients with sepsis were 31.2 microgram/mL (interquartile range, 22.5-47.7 microgram/mL). Median endotoxin levels at study entry were more highly elevated (515 vs. 230 pg/mL; P<.01), and LBP levels were less highly elevated (28.0 vs. 33.2 microgram/mL; P<.05) in nonsurvivors than survivors over the 28-day study period. No correlation was found between endotoxin and LBP levels. The quantitative level of both endotoxin and LBP may have prognostic significance in patients with severe sepsis.

Voice problems among teachers: differences by gender and teaching characteristics.

This study describes the effects of teaching activities on voice problems in male (n = 274) and female teachers (n = 280). Over 38% of the teachers studied complained that teaching had an adverse impact on their voice and 39% of those had cut back teaching activities as a result. Compared to males, female teachers more frequently reported a voice problem (38% vs. 26%, p<.05), acute (p<.05), and chronic (p<.05) voice problems, six specific voice symptoms, and five symptoms of physical discomfort. However, there were no gender differences in the perception that a voice problem adversely affected their current or future teaching career. For every type of course taught, women had a higher probability of reporting voice problems compared to men: odds ratio (OR) = 1.7-2.1. Compared with other courses, the teaching of physical education also was associated with an increased risk of developing a voice problem (OR = 3.7, 95% CI: 1.4-9.4) independent of gender, age, hours/day, or years taught. This is the first study to show that in the same occupation, females report a higher frequency of vocal symptoms than males even when teaching characteristics and years employment are similar.

Physical activity, physical function, and the risk of breast cancer in a prospective study among elderly women.

BACKGROUND: Accumulating evidence suggests that physical activity may protect against the development of breast cancer, but less is known about the role of modest physical activity during the postmenopausal years and in the context of physical function. METHODS: We evaluated this association in the Iowa 65+ Rural Health Study, a population-based, prospective cohort study of elderly adults. The cohort was linked to a population-based cancer registry for the years 1973-93, and the at-risk cohort consisted of 1806 women ages 65 to 102 years with an in-person baseline interview in 1982 and with no documented cancer between 1973 and the baseline interview. Through 1993 (16,857 person-years of follow-up) there were 46 incident cases of breast cancer. RESULTS: Greater level of physical activity in women with no physical disabilities was inversely associated with breast cancer risk (p for trend = .01). Compared to inactive women with no physical disability, women reporting moderate (age-adjusted relative risk [RR] = 0.5, 95% confidence interval [CI] 0.3-1.1) or high (age-adjusted RR = 0.2, 95% CI .05-0.9) activity levels were at decreased risk of breast cancer. Women with any disability were also at decreased risk of breast cancer compared to inactive women with no disability (age-adjusted RR = 0.4; 95% CI 0.2-0.9). Adjustment for education, body mass index, age at menarche, age at menopause, previous use of hormone replacement therapy, pregnancy history, systolic blood pressure, smoking, and alcohol use did not alter these associations. In addition, these associations were similar after exclusion of cases occurring during the first two years of follow-up, after adjusting for the number of doctor visits, and after stratifying by stage at diagnosis. CONCLUSIONS: These data suggest that postmenopausal activity level, after accounting for physical disability, is inversely associated with breast cancer risk.

Early conjunctival changes following treatment with metipranolol and preservatives are not reversible with dexamethasone.

BACKGROUND: Topical medication for the treatment of glaucoma alters the cellular and extracellular composition of the superficial and deep conjunctival layers. We sought to determine whether, after short-term use of metipranolol with preservatives, subsequent application of steroids or metipranolol without preservatives affects these conjunctival changes. METHODS: Rabbits received topical metipranolol over a period of 6 months. For the following 2 months, one group received metipranolol without preservatives, and another group steroids. For controls, animals were treated with preservatives only or metipranolol with preservatives for 6 months. Superior bulbar conjunctiva was examined by light microscopy, immunohistochemistry, and transmission electron microscopy. RESULTS: On light microscopic and immunohistochemical examination of conjunctival specimens from all groups, there was an increase of subepithelial collagen deposition in all treated groups. Treatment with steroids or preservative-free metipranolol did not alter the initial effects. By electron microscopy, additional extracellular matrix changes were seen as well as degenerative changes of tissue fibroblasts. CONCLUSION: The animal model used was able reliably to produce conjunctival changes following antiglaucomatous therapy. The changes seen were early changes, because there was no increase of inflammatory cells. Steroids did not significantly affect the changes. The beneficial effect of steroids used prior to glaucoma surgery remains controversial.

An introduction to time-trend analysis.

Healthcare professionals often are presented with data that appear to indicate an upward or downward trend over time. For example, admissions of acquired immunodeficiency syndrome (AIDS) patients appear to be increasing, cesarean section rates appear to be decreasing, or nosocomial pneumonia rates appear to be increasing. Critical decisions sometimes are based on such trends, which often are presented without a statistical analysis. Those responsible for decision making may be left wondering whether these apparent trends represent only chance variation. Graphs showing trends over time generally present one of three kinds of outcome data: counts (eg, three AIDS admissions), proportions (eg, 10 cesarean sections per 100 total deliveries), or person-time data (eg, 13 cases of nosocomial pneumonia per 10,000 patient days). Using familiar examples and a minimum of technical language, we illustrate the analysis of time trends.

Association of smoking, body mass, and physical activity with risk of prostate cancer in the Iowa 65+ Rural Health Study (United States).

Smoking, obesity, alcohol, and physical activity can modulate the endocrine system, and therefore have been hypothesized to play a role in the etiology of prostate cancer. At baseline in 1982, 80 percent (n = 3,673) of the noninstitutionalized persons age 65+ in two rural Iowa (United States) counties were enrolled into the Iowa 65+ Rural Health Study. Follow-up for mortality was complete through 1993, and cancer experience was determined by linkage to the State Health Registry of Iowa cancer database for the years 1973-93. We analyzed data on 1,050 men aged 65 to 101 years (mean age 73.5) with a full interview in 1982 and with no documented cancer in the 10 years prior to baseline. Through 1993 (8,474 person-years of follow-up), there were 71 incident cases of prostate cancer. In a multivariate model, age, cigarette smoking (relative risk [RR] = 2.9 for currently smoking 20 or more cigarettes per day compared with never smoking; P trend = 0.009), greater body mass index (BMI) (wt/ht2) (RR = 1.7 for BMI > 27.8 kg/m2 compared with < 23.6; P trend = 0.1), and greater level of physical activity (RR = 1.9 for high activity level cf inactive; P trend = 0.05) were independent predictors of prostate cancer, and these associations were stronger for regional or disseminated disease at diagnosis. Percent change in BMI from age 50 to baseline was associated positively with risk (P trend = 0.01), and this association appeared to be stronger in heavier men. There were no data on diet. These findings suggest that smoking, overweight, and weight gain in later life are risk factors for prostate cancer and support a hormonal etiology; the positive association for physical activity confirms some previous reports, but remains without a credible biologic mechanism.

Urinary incontinence in rural older women: prevalence, incidence and remission.

OBJECTIVES: To determine the prevalence, incidence, and remission rates of urinary incontinence in a large group of older women over a 6-year time span and to assess factors associated with incontinence incidence and remission. DESIGN: Longitudinal cohort study. SETTING: Two rural counties in Iowa. PARTICIPANTS: 2025 women aged 65 years or older residing in rural Iowa, enrolled in the Iowa 65+ Rural Health Study of EPESE (Establishment of Populations for Epidemiologic Studies of the Elderly) were interviewed in person annually for 6 years; specific responses to queries about urinary incontinence were given at baseline, 3-, and 6-year intervals. MEASUREMENTS: Conditional multivariate logistic regression analysis was done to assess the relationship between incontinence symptoms and various factors previously found to be related to incontinence. RESULTS: The baseline prevalence of urge incontinence was 36.3%, and of stress incontinence it was 40.3%. For urge incontinence, the 3-year incidence and remission rates between the third and sixth years were 28.5% and 22.1%, respectively. For stress incontinence, the 3-year incidence and remission rates between years 3 and 6 were 28.6% and 25.1%, respectively. Seventy-six percent and 84% of women who reported no urge or stress incontinence, respectively, at the baseline interview were continent at both follow-up interviews. The only significant factors related to changes in incontinence status were age, which was associated with an increased incidence of urge incontinence (OR 1.11, P = .017, 95% CI 1.019-1.203), and improvement in activities of daily living, which was associated with a increased remission of urge incontinence (OR 0.50, P = .015, 95% CI 0.28-0.9) CONCLUSION: In some older women, urinary incontinence is a dynamic state, with women moving back and forth along a continuum between continence and incontinence. These results are tempered by limitations of the study, which include its questionnaire design and lack of ability to detect potential treatment effect.

Analysis of change in self-reported physical function among older persons in four population studies.

Change in self-reported physical function was examined using baseline and 5 years of follow-up data between 1982 and 1991 from the four Established Populations for Epidemiologic Studies of the Elderly studies. In East Boston, Massachusetts (n = 3,809), Iowa and Washington Counties, Iowa (n = 3,673), New Haven, Connecticut (n = 2,812), and North Carolina (n = 4,163), noninstitutionalized persons aged 65 years and older were asked a series of questions to assess their physical function: a modified Katz Activities of Daily Living (ADL) scale, three items from the Rosow-Breslau Functional Health Scale, and questions on physical performance, adapted from Nagi, as well as information on demographic, social, and health characteristics. Longitudinal statistical analyses (random effects and Markov transition models) were used to evaluate improvement, stability, and deterioration in functional ability at both an individual and a population level over multiple years of data. The average decline in physical function associated with age was found to be greater than previous cross-sectional studies have suggested, and the rate of decline increased with increasing age. Considerable individual variation was evident. Although many people experienced declines, a smaller but substantial portion experienced recovery. Women reported a greater rate of decline in physical function and were less likely to recover from disability.

Coordination of velopharyngeal muscle activity during positioning of the soft palate.

The relative contributions of the levator veli palatini, palatoglossus, and palatopharyngeus muscles were assessed relative to a range of positions of the velopharynx during production of the vowels [a] and [i] by four normal adult speakers. The results indicate that velopharyngeal positioning is determined by the relative contributions of the levator veli palatini, palatoglossus, and palatopharyngeus muscles. There was an increase in coefficients of determination (i.e., amount of closure level variability explained) when activity levels of all three muscles are included in the statistical model compared to activity in any one muscle analyzed independently. Both consistent and inconsistent relations among activity levels in the three velopharyngeal muscles studied were observed across speaker and vowel produced.

Mortality and physical functioning in epidemiologic studies of three older populations.

Mortality experienced in the first three years of follow-up for three Established Populations for Epidemiologic Studies of the Elderly (EPESE) is examined in relation to the participants' self-reported functional ability. In East Boston, Massachusetts (N = 3,812), Iowa and Washington Counties, Iowa (N = 3,673), and New Haven, Connecticut (N = 2,812), noninstitutionalized persons aged 65 and older were asked a series of questions to determine their functional status. These measures, used in logistic regression analyses of the mortality data, showed that an increased number of reported disabilities significantly increased the risk of mortality over and above the effects of the age and sex of the participant, or the methodological differences among the sites. Disabilities in gross mobility (e.g., ability to walk a half mile, climb stairs, or perform heavy work around the house) were more strongly related to mortality than were measures of activities of daily living.

Risk due to inactivity in physically capable older adults.

OBJECTIVES: This study examined the association between recreational physical activity among physically capable older adults and functional status, incidence of selected chronic conditions, and mortality over 3 and 6 years. METHODS: Data are from three sites of the Established Populations for Epidemiologic Studies of the Elderly. RESULTS: A high level of recreational physical activity reduced the likelihood of mortality over both 3 and 6 years. Moderate to high activity reduced the risk of physical impairments over 3 years; this effect diminishes after 6 years. A consistent relationship between activity and new myocardial infarction or stroke or the incidence of diabetes or angina was not found after 3 or 6 years. CONCLUSIONS: Findings suggest that physical activity offers benefits to physically capable older adults, primarily in reducing the risk of functional decline and mortality. Future work must use more objective and quantifiable measures of activity and assess changes in activity levels over time.

Established populations for epidemiologic studies of the elderly: study design and methodology.

A project initiated by the intramural Epidemiology, Demography and Biometry Program of the National Institute on Aging, entitled "Established Populations for Epidemiologic Studies of the Elderly" (EPESE), has developed information on death, chronic conditions, disabilities, and institutionalization for representative samples of elderly people living in communities. The EPESE consists of prospective epidemiologic studies of approximately 14,000 persons 65 years of age and older in four different communities: East Boston, Massachusetts; two rural counties in Iowa; New Haven, Connecticut; and segments of five counties in the north-central Piedmont area of North Carolina. The study design includes an initial baseline household interview followed by continued surveillance of morbidity and mortality. Participants are re-contacted annually in conjunction with the collection of data on cause of death and factors related to hospitalization and nursing home admissions. Concurrently, the investigators developed substudies focused on specific problems of the elderly. The value of this research lies in the longitudinal design which allows for analyses aimed at identifying risk factors of diseases, disabilities, hospitalizations, institutionalization, and mortality.

Use of medications by persons 65 and over: data from the established populations for epidemiologic studies of the elderly.

Data were analyzed from household interviews of four population-based cohorts comprising the Established Populations for Epidemiologic Studies of the Elderly to estimate the prevalence of prescription and nonprescription medication use among community-living elderly and to examine sociodemographic and health factors related to medication use. Prescription drugs were used by 60-68% of men and 68-78% of women. Nonprescription drugs were used by 52-68% of men and 64-76% of women. Use of prescription medications generally increased with age although use of nonprescription drugs was not associated with age. Men and women who smoked or used alcohol in the preceding year frequently took medications. Those who reported more depressive symptoms, impairments in physical functioning, hospitalizations, and had poorer self-perceived health status were most likely to take medications. However, 10-29% of respondents with fair or poor self-perceived health took no prescription medications, and 3-13% took neither prescription nor nonprescription medications. While further research appears warranted into potential overmedication of elders, particularly those with many depressive symptoms, these data suggest that studies of potential underuse among elders with poor health are equally important.

Correct placement of epidural steroid injections: fluoroscopic guidance and contrast administration.

We prospectively evaluated 316 caudal-approach epidural steroid injections given by staff radiologists and residents in our department over a 1-year period. Needle placement was checked with fluoroscopy and corrected if necessary. When the needle tip was within the sacral canal, nonionic contrast material was injected. If epidural contrast was not observed, the needle tip was repositioned. Of 111 procedures performed by physicians who had given fewer than 10 epidural steroid injections, 53 (47.7%) resulted in correct nonfluoroscopically directed placement of the needle. For physicians who had performed between 10 and 50 such procedures, 62 (53.4%) of 116 had correct nonfluoroscopically directed placement. For staff physicians, 55 (61.7%) of 89 placements were correct. Even when the sacral hiatus was easily palpated and a staff physician was confident that he or she was within the epidural space, fluoroscopy revealed incorrect placement 14.2% of the time (seven of 49 procedures). In addition, when the needle was positioned within the sacral canal and no blood was evident on Valsalva maneuver or aspiration, the injection was venous in 29 of 316 procedures (9.2%). The presence of blood on the needle stylus was not a reliable indicator of venous placement of the needle. Our findings indicate that fluoroscopy is essential for correct placement of epidural steroid injection. Contrast administration is necessary to avoid venous injection of steroids.

Nephrotoxicity from contrast material in renal insufficiency: ionic versus nonionic agents.

Controversy exists over whether use of low-osmolality contrast agents is of any benefit in mitigating the risk of contrast material-induced nephrotoxicity (CN) in patients with impaired renal function. To test this hypothesis, 101 adult inpatients with high serum creatinine levels (range, 1.4-2.4 mg/dL [120-210 mumol/L]) undergoing contrast material-enhanced computed tomography were randomized to receive ionic or nonionic (low-osmolality) contrast agents in a uniform dose. Changes in serum creatinine level at 48 hours were measured. Seven (14%) of the 50 patients receiving ionic contrast media experienced an increase of 25% or more in serum creatinine level. Only one (2%) of the 51 patients receiving nonionic contrast agents experienced such an increase, a statistically significant difference (P less than .05). In the subset of 25 diabetic patients, the difference was of a similar magnitude. These data suggest that ionic contrast media are more likely than nonionic contrast agents to cause mild exacerbation of renal insufficiency when given intravenously. However, there were no cases of clinically important CN in the study.

Glenoid labrum: evaluation with MR imaging.

Fifteen patients with shoulder instability and nine asymptomatic volunteers were studied with magnetic resonance (MR) imaging. The shoulder joint was visualized by means of arthroscopy or surgery in all patients. Ten patients had abnormalities of the glenoid labrum. Two musculoskeletal radiologists interpreted the MR images of the patients and volunteers without knowledge of the clinical history or surgical results. The surgical and arthroscopic results were used as the standard of reference in symptomatic patients. Observer A achieved a sensitivity of 44.4% and a specificity of 66.7%; observer B had a sensitivity of 77.8% and a specificity of 66.7%. In addition to the poor sensitivities and specificities, there was substantial intra- and interobserver variability. Assuming that the shoulders of the asymptomatic volunteers were normal, the specificities were 100.0% and 88.9% for observers A and B respectively. In this small study, axial MR imaging was relatively insensitive and nonspecific in the evaluation of labral lesions. Further study will be necessary to determine the utility and limits of MR imaging in this regard.

Perceived purpose of prescription drugs: the Iowa 65+ Rural Health Study.

In order to assess elderly patients' knowledge of their medications, the Iowa 65+ Rural Health Study asked a rural, elderly population the purpose of their prescription drugs. Ten percent of all drug purposes reported were considered inappropriate by our criteria. There was some variability between therapeutic categories and their frequency of purpose misperception. For 40 percent of drugs whose purpose was inappropriate, the respondent reported another drug for which that purpose would have been appropriate. Respondents were as likely to state a medication's appropriate purpose whether it had been dispensed by a pharmacy or a physician. The highest percentage of drugs whose purpose was appropriately perceived was dispensed by mail-order pharmacies.

Prevalence and characteristics of multiple analgesic drug use in an elderly study group.

With few exceptions, use of multiple analgesic drugs achieves dubious increases in analgesia while placing elders at increased risk of the many potential adverse effects of analgesic drugs. The potential for duplication of analgesic therapy among the elderly is great due to prevalent painful chronic conditions and the variety of prescription and nonprescription analgesic remedies available. The prevalence of multiple analgesic product use and patterns of concurrent use of different analgesic categories was investigated in a geographically defined population of persons 65 years of age and older. The demographic characteristics of users of multiple analgesic drug products were examined, as were their smoking status, alcohol use, lifetime history rates of major illnesses, physical functioning, pain experiences, memory performance, and depressive symptoms. A substantial proportion of analgesic users reported taking multiple products in the preceding 2 weeks (14.4% of female and 10.5% of male analgesic users). Men who reported pain in the preceding year were more likely to use multiple analgesic products. Women who experienced pain or limited physical functioning, or who had higher depressive symptom scores or a life-time history of ulcers were most likely to use multiple analgesic products. Thus, although some users of multiple analgesic products reported significant pain, several other factors were shown to be related to the phenomenon of multiple use.

Statistical analysis of K 2 x 2 tables: a comparative study of estimators/test statistics for association and homogeneity.

In order to control for confounding variables, epidemiologists often obtain data in the form of a 2 x 2 table. One variable is usually the disease status, while the other variable represents a dichotomous exposure variable that is suspected of being a risk factor. If a confounding variable is present, the data are often stratified into several 2 x 2 tables. The objectives of the analysis are to test for the association between the suspected risk factor and the disease and to estimate the strength of this relationship. Before estimating a common odds ratio, it is important to check whether the odds ratios are homogeneous. This paper presents the results of a Monte Carlo study that was performed to determine the size and power of a number of tests of association and homogeneity when the data are sparse. We also evaluated the performance of three estimators of the common odds ratio. For the Monte Carlo studies, equal numbers of cases and controls were used in a wide variety of sparse data situations. On the basis of these studies, we recommend the Breslow-Day test for nonsparse data, and the T4 and T5 statistics for sparse data to test for homogeneity. The Mantel-Haenszel test of association is recommended for sparse and nonsparse data sets. With sparse data, none of the odds ratio estimators are entirely satisfactory.

Self-evaluated health and mortality among the elderly in New Haven, Connecticut, and Iowa and Washington counties, Iowa, 1982-1986.

The ability of global self-evaluations of health to predict survival in follow-up studies is tested in two samples of elderly, noninstitutionalized adults. Data from the Yale Health and Aging Project, New Haven, Connecticut (n = 2,812), and the 65+ Rural Health Study, Iowa and Washington counties, Iowa (n = 3,673), were used to investigate the association between 1982 self-evaluated global health status (excellent, good, fair, poor) and survivorship from 1982 to 1986. Despite extensive controls for physical health status in the form of measures of disabilities and chronic conditions, sociodemographic characteristics, and health risk behaviors at the beginning of the follow-up period, and the use of analytic techniques which take into account the stratified sample design of the New Haven data, poor self-perceptions of health significantly increase the risk of mortality. Adjusted odds ratios for the extreme categories ("poor" as compared with "excellent") for New Haven men and women were 5.33 (95% confidence interval (CI) 1.93-14.75) and 2.99 (95% CI 1.30-6.91), respectively; for Iowa men and women they were 4.84 (95% CI 2.22-10.57) and 3.16 (95% CI 1.49-6.71). Respondents reporting "fair" and "good" health also show elevated risks of mortality in dose-response fashion. Self-perceptions of health status appear to be a factor of unique prospective significance in mortality studies.