James C. Reading

Risk factors for postoperative pneumonia

Abstract Prospectively studied were 520 patients undergoing elective thoracic, upper abdominal and lower abdominal surgeries to analyze risk factors for postoperative pneumonias. Over-all, pneumonias developed in 91 of the 520 patients studied (17.5 percent). The acquisition of pneumonia was highly associated with preoperative markers of the severity of underlying diseases such as low serum albumin concentrations on admission (P We were able to identify risk factors for pneumonia and to define a subpopulation of patients in which the risk of pneumonia was negligible. The acquisition of pneumonia by a low-risk patient should alert the physician to the possibility of a potentially preventable nosocomial infection.

A comparison of calcium, vitamin D, or both for nutritional rickets in Nigerian children.

BACKGROUND Nutritional rickets remains prevalent in many tropical countries despite the fact that such countries have ample sunlight. Some postulate that a deficiency of dietary calcium, rather than vitamin D, is often responsible for rickets after infancy. METHODS We enrolled 123 Nigerian children (median age, 46 months) with rickets in a randomized, double-blind, controlled trial of 24 weeks of treatment with vitamin D (600,000 U intramuscularly at enrollment and at 12 weeks), calcium (1000 mg daily), or a combination of vitamin D and calcium. We compared the calcium intake of the children at enrollment with that of control children without rickets who were matched for sex, age, and weight. We measured serum calcium and alkaline phosphatase and used a 10-point radiographic score to assess the response to treatment at 24 weeks. RESULTS The daily dietary calcium intake was low in the children with rickets and the control children (median, 203 mg and 196 mg, respectively; P=0.64). Treatment produced a smaller increase in the mean (+/-SD) serum calcium concentration in the vitamin D group (from 7.8+/-0.8 mg per deciliter [2.0+/-0.2 mmol per liter] at base line to 8.3+/-0.7 mg per deciliter [2.1+/-0.2 mmol per liter] at 24 weeks) than in the calcium group (from 7.5+/-0.8 [1.9+/-0.2 mmol per liter] to 9.0+/-0.6 mg per deciliter [2.2+/-0.2 mmol per liter], P<0.001) or the combination-therapy group (from 7.7+/-1.0 [1.9+/-0.25 mmol per liter] to 9.1+/-0.6 mg per deciliter [2.3+/-0.2 mmol per liter], P<0.001). A greater proportion of children in the calcium and combination-therapy groups than in the vitamin D group reached the combined end point of a serum alkaline phosphatase concentration of 350 U per liter or less and radiographic evidence of nearly complete healing of rickets (61 percent, 58 percent, and 19 percent, respectively; P<0.001). CONCLUSIONS Nigerian children with rickets have a low intake of calcium and have a better response to treatment with calcium alone or in combination with vitamin D than to treatment with vitamin D alone.

Early Undifferentiated Connective Tissue Disease: III. Outcome and Prognostic Indicators in Early Scleroderma (Systemic Sclerosis)

Scleroderma, or systemic sclerosis, varies widely in its presentation and course. Many patients with scleroderma have a disease course of 10 to 20 years [1-4], but some patients experience a rapidly progressive form of disease characterized by early organ failure and death. Of 91 patients studied retrospectively by Lally and colleagues [3], 16 developed renal or cardiorespiratory failure (or both) an average of 15.8 months after the onset of symptoms; 11 of these 16 patients died. Retrospective assessments are inherently weighted toward the selection of patients with a longer disease duration, and patients experiencing early death or rapidly progressive disease may be under-represented. A few clinical studies and therapeutic trials have targeted patients with a disease duration of less than 5 years [3-5]; however, additional prospective information on the course and prognosis of patients with early scleroderma is needed to make appropriate risk/benefit decisions about potentially toxic therapies. Recently, a prospective study was done in 410 patients with early undifferentiated or early defined connective tissue disease [6]. Selecting 48 patients with early scleroderma from this cohort, we analyzed short-term outcomes and identified some features occurring within the first year of disease that may be useful in distinguishing patients at high risk for an unfavorable outcome. Methods The Cooperative Systematic Studies of the Rheumatic Diseases Program is funded under a National Institute of Arthritis and Musculoskeletal Diseases contract through the Coordinating Center at the University of Utah, Salt Lake City, Utah, and includes 10 centers participating in the study of early undifferentiated connective tissue disease. Outpatients and inpatients seen at participating centers were eligible for the study if they met diagnostic criteria for rheumatoid arthritis, scleroderma, systemic lupus erythematosus, or poly/dermatomyositis [7-10] and had experienced symptoms for less than 1 year. Patients who had features of a connective tissue disease, including Raynaud phenomenon, unexplained polyarthritis, or 3 of 11 findings characteristic of connective tissue disease, but who did not meet established criteria for a specific connective tissue disease were classified as having undifferentiated connective tissue disease. Patients were evaluated at baseline and at follow-up intervals of 1, 3, and 5 years. Details on data collection and on the clinical and laboratory features of the patients with early undifferentiated connective tissue disease have been described previously [6, 11]. Enrollment for the study began in July 1982 and was completed in June 1987. Survival status was confirmed through at least 5 years after symptom onset in all cases except one (patient lost to follow-up after 1.6 years). A diagnosis of scleroderma was made in 52 patients (in 46 within 1 year of symptom onset and in 6 within 4 years of symptom onset). Four of these patients (including 2 of 6 diagnosed after the baseline evaluation) developed overlap syndromes during the 5-year follow-up period and were excluded from the study, leaving 48 patients for analysis. Deaths and causes of death were reported to the Coordinating Center; every possible effort was made to confirm the cause of death through hospital records and autopsy reports from the participating centers. Five patients died at home, on the way to the hospital, or shortly after arrival at the hospital. Sclerodermatous skin findings on physical examination were categorized as follows: sclerodactyly (involvement distal to the metacarpophalangeal joints); acrosclerosis (involvement distal to elbows and knees); or generalized or diffuse scleroderma. A skin score was not determined. Physical findings for each organ system were recorded as a yes or no response to a list of abnormal findings. Twelve cardiorespiratory signs were assessed on the baseline physical examination: These included the presence or absence of rales, wheezes, pleural or pericardial rubs, pleural effusion, systolic or diastolic murmurs, abnormal second heart sounds, cardiomegaly, arrhythmia, dependent edema, and tachycardia (pulse 100 beats/min). All patients had routine hematology and biochemical laboratory tests. Many patients also had a determination of erythrocyte sedimentation rate (Westergren method) (n = 47), pulmonary function tests (n = 43), an electrocardiogram (n = 40), a chest radiograph (n = 40), and the Schirmer test. Serum specimens from all patients were analyzed for serologic markers of rheumatic disease at the Centers for Disease Control [11]. In addition, frozen serum specimens from 45 of the 48 patients with scleroderma were analyzed at Specialty Laboratories, Inc. (Santa Monica, California): Interleukin-2 levels were assessed by enzyme-linked immunosorbent assay (ELISA); soluble interleukin-2 receptor levels by ELISA; and neopterin levels by radioimmunoassay; anti-Scl-70 antibody levels by ELISA; and anticentromere antibody titer by immunofluorescence assay. Lung diffusing capacity was considered to be abnormal if it was less than 70% of the predicted diffusing capacity. Chest radiographs were considered to be abnormal if infiltrates, effusions, pleural thickening, or heart enlargement was present. Electrocardiograms were considered to be abnormal if evidence of arrhythmia, heart block, ventricular enlargement, repolarization abnormalities, significant shift in axis, or infarction was found. For the purposes of our study, nonspecific ST or T-wave abnormalities were not considered to be abnormal. Baseline clinical, laboratory, and other features of patients with early death were compared with those of survivors. Mean values were compared using the Student t-test. Comparisons between dichotomous variables were done using chi-square distribution with Yates correction. Life-table analyses using Kaplan-Meier survival estimation [12] and Mantel-Haenszel statistics [13] were done to predict survival rates for the group of patients with early scleroderma and the various subgroups generated by stratification based on selected variables. Variables were evaluated using univariate Cox proportional-hazards analysis for their ability to predict survival [14]. The variables found to be most significant, as determined by univariate Cox proportional-hazards analysis, and for which less than 10% of data were missing, were then evaluated by multivariate Cox analysis with stepwise regression modeling. We did not apply the Bonferroni correction to our results; however, because of the many variables compared, we defined statistical significance by a probability level of 0.01. Results Forty-eight patients with scleroderma were enrolled in the study. One patient was lost to follow-up 1.6 years after symptom onset, and the data gathered on her were used only in the survival and Cox analyses. During the 5-year follow-up period, 15 of the 47 evaluable patients with early scleroderma died. Kaplan-Meier estimation yielded overall survival rates at 1, 3, and 5 years after symptom onset of 92%, 75%, and 68%, respectively (Figure 1). Five patients died within 1 year of symptom onset. The cohort of patients with scleroderma accounted for 41% of all early deaths recorded for the entire study population of 410 patients. The causes of death are summarized in Table 1. Multiorgan involvement was frequently observed at the time of death, although pulmonary or cardiac system failure (or both) was thought to be the immediate cause of death in 8 of the 15 patients who died. Renal crisis was substantiated or suspected in 4 of the patients who died. The time from symptom onset to death was similar for those dying of renal causes (21 11 months) and those dying of cardiopulmonary causes (25 17 months). Table 1. Suspected Immediate Causes of Death, Average Age at Death, and Survival in Patients with Early Scleroderma* Figure 1. Cumulative survival probabilities: Kaplan-Meier survival curve with Greenwood confidence limits from onset of symptoms for the 48 early scleroderma patients. Clinical Features In Table 2, baseline characteristics of patients who died within 5 years after symptom onset are compared with those of the survivors. Twelve of the 15 (80%) patients who died had at least one abnormal cardiopulmonary sign at baseline compared with 13 of 32 (41%) survivors (P = 0.03). Among individual cardiopulmonary findings, resting heart rate was significantly different between survivors (79 13 beats/min; range, 50 to 110 beats/min) and patients who died (93 12 beats/min; range, 70 to 120 beats/min) (P = 0.001). Baseline blood pressure was similar in the subgroups (survivors: 120 17/76 12 mm Hg; patients who died: 127 27/78 16 mm Hg; P > 0.3), as was the frequency of chest radiographic, pulmonary function, and electrocardiographic abnormalities (P = 0.09). Table 2. Baseline Features of Patients with Early Scleroderma Who Survived and of Those Who Died* Chest pain, dyspnea, orthopnea, dependent edema, cough, and wheezing were common complaints; 57% of the entire group had at least one symptom. Dyspnea was the most common single cardiorespiratory complaint (36%). No significant difference in frequency of cardiopulmonary symptoms was detected between those who died and those who survived. Ninety-two percent of our patients developed skin involvement within 1 year of symptom onset, implying that patients with gradual-onset scleroderma were not included in our study. Four of the 48 patients did not have diagnosable scleroderma at their first visit, but they did develop skin disease within 3 years of follow-up (or within 4 years of disease onset). At entry, two patients had Raynaud phenomenon only and two were diagnosed with undifferentiated connective tissue disease. When baseline variables for these 4 patients with intermediate-onset scleroderma were compared with those of the remaining 44 patients with earlier-onset disease, no significant differences were

Thyroid disease associated with exposure to the Nevada nuclear weapons test site radiation: A reevaluation based on corrected dosimetry and examination data

Background: A study was begun in 1965 to 1966 to determine whether children exposed to radioactive iodine from nuclear weapons testing at the Nevada Test Site from 1951 through 1962 were at higher risk of thyroid disease. In 1993, we reported that among those examined in 1985 to 1986 (Phase II) there was an association between radiation from the Nevada Test Site and thyroid neoplasms. Methods: We reevaluated the relationship between exposure to Nevada Test Site fallout and thyroid disease using newly corrected dose estimates and disease outcomes from the Phase II study. A prospective cohort of school children 12 to 18 years old living in Utah, Nevada, and Arizona was first examined for thyroid disease in 1965 to 1966 and reexamined in 1985 to 1986. In the Phase II report, 2497 subjects formed the basis for this analysis. Thyroid disease, including thyroid neoplasms and thyroiditis, was expressed as cumulative incidence and risk ratios (RRs) with a dose–response expressed as excess risk ratio (ERR/Gy). Results: The RR between thyroid radiation dose in the highest dose group and thyroid neoplasms increased from 3.4 (in the earlier analysis) to 7.5. The RR for thyroiditis increased from 1.1 to 2.7 with an ERR/Gy of 4.9 (95% confidence interval = 2.0 to 10.0). There were too few malignant thyroid neoplasms to estimate risk. Conclusions: Persons exposed to radioactive iodine as children have an increased risk of thyroid neoplasms and autoimmune thyroiditis up to 30 years after exposure.

The use of generalized estimating equations in the analysis of motor vehicle crash data

The purpose of this study was to determine if it is necessary to use generalized estimating equations (GEEs) in the analysis of seat belt effectiveness in preventing injuries in motor vehicle crashes. The 1992 Utah crash dataset was used, excluding crash participants where seat belt use was not appropriate (n=93,633). The model used in the 1996 Report to Congress [Report to congress on benefits of safety belts and motorcycle helmets, based on data from the Crash Outcome Data Evaluation System (CODES). National Center for Statistics and Analysis, NHTSA, Washington, DC, February 1996] was analyzed for all occupants with logistic regression, one level of nesting (occupants within crashes), and two levels of nesting (occupants within vehicles within crashes) to compare the use of GEEs with logistic regression. When using one level of nesting compared to logistic regression, 13 of 16 variance estimates changed more than 10%, and eight of 16 parameter estimates changed more than 10%. In addition, three of the independent variables changed from significant to insignificant (alpha=0.05). With the use of two levels of nesting, two of 16 variance estimates and three of 16 parameter estimates changed more than 10% from the variance and parameter estimates in one level of nesting. One of the independent variables changed from insignificant to significant (alpha=0.05) in the two levels of nesting model; therefore, only two of the independent variables changed from significant to insignificant when the logistic regression model was compared to the two levels of nesting model. The odds ratio of seat belt effectiveness in preventing injuries was 12% lower when a one-level nested model was used. Based on these results, we stress the need to use a nested model and GEEs when analyzing motor vehicle crash data.

Uses and abuses of analysis of covariance in clinical trials

Measurement of improvement in clinical trials in chronic diseases commonly compares baseline data to endpoint values by performing t-tests or analysis of variance (ANOVA) on raw gains or percentage changes. This procedure can be misleading and the use of an analysis of covariance (ANCOVA) should be considered. Properly used, ANCOVA increases statistical power in a clinical trial. However, its advantage over t-tests can be nullified by small numbers of patients, violations of assumptions, and incorrect application of the techniques. An evaluation of ANCOVA in chronic disease studies is given, with examples of its strengths and weaknesses as seen in several drug trials in the rheumatic diseases. Recommendations on its use and a decision tree for the nonstatistician are provided.

Clinical Validation of a Noninvasive, Raman Spectroscopic Method to Assess Carotenoid Nutritional Status in Humans

Background: Carotenoids are an important group of phytonutrients that are abundant in fruits and vegetables. Epidemiological and clinical intervention studies have implied the presence of protective qualities of these nutrients against the development of a variety of chronic diseases. Previously, human carotenoid status has been assessed in serum and tissue using high-performance liquid chromatography (HPLC) methodology. Recently, a Raman spectroscopy (RS)–based photonic method has been developed to accurately and noninvasively measure the carotenoid concentration in human skin. Objectives: (1) To validate skin RS methodology against standard serum carotenoid measurements by HPLC and (2) to establish and compare the reliability of the 2 methods. Design: This study included 372 healthy adults who provided 3 blood samples and 3 RS skin carotenoid measurements within an 8-day period; each day-matched blood sample and RS determination was spaced by ≥48 hours. Results: Consistent positive correlations were observed for each of 3 separate same-day correlation plots of total serum versus RS skin carotenoids. Overall estimate of the line of best fit from analysis of covariance, using all 3 samples (n  =  1116), yielded a Pearson correlation of R  =  0.81 (r2  =  0.66; p < 0.001). Based on analysis of variance, RS skin carotenoid methodology exhibited 0.9% less variance over the 3 tests than serum carotenoids by the HPLC method (p < 0.03). Conclusions: RS accurately measures total carotenoids in human skin with less intra-individual variability than measurement of serum carotenoids by HPLC analysis. RS technology is a valid and reliable noninvasive method to rapidly assess carotenoid nutritional status in humans.

Pre-hospital emergency medical services: a population based study of pediatric utilization

Objectives—To examine emergency medical services (EMS) usage by children in one state. Methods—Dispatch of an EMS vehicle in response to a call in the US is referred to as a “run”. Runs for Utah for 1991–92 were linked to corresponding hospital records. Abbreviated injury severity scores (AISs) were assigned using ICDMAP-90 software. Results—For the two year period there were at least 15 EMS runs per 100 children per year, with incomplete reporting from rural areas. EMS response and scene times were similar for all age groups, but interventions were less frequent for children under 5 years of age. When the principal AIS region of injury was the head, neck, or face, cervical immobilization was less frequent for children less than 5 years of age (54%) than for older children (76%) and immobilization was associated with improved outcome, using the crude measure of lower hospital charges. There was a similar association between splinting of upper extremity fractures and reduced hospital charges. Both associations did not appear to be due to differences in injury severity. Conclusions—The majority of EMS use by children is for trauma. Children less than 5 years of age are less likely to have an EMS intervention than older children. Whether the lower frequency of interventions is due to the lack of properly sized equipment on the vehicle, or to other factors, is undetermined.

The Role of Control in Depression, Anxiety, and Life Satisfaction among Visually Impaired Older Adults

Abstract Two groups of visually impaired older adults, minimally (n = 40) and severely impaired (n = 40), were compared on depression, anxiety, life satisfaction, and various dimensions of control....

Trends of behavioral risk factors in motor vehicle crashes in Utah, 1992–1997

OBJECTIVE Measure changes in the prevalence of behavioral factors including police-reported fatigue and alcohol intoxication, as well as self-reported seatbelt use, and assess their effect on hospitalization or death after a motor vehicle crash. METHODS Probabilistic linkage was used to match drivers in motor vehicle crashes with hospital discharge records for the years 1992-1997. Frequencies of specific behavioral factors were evaluated using the Cochran-Armitage test for trend. Odds ratios and corresponding 95% confidence intervals were calculated using generalized estimating equations (GEEs) with crash and driver characteristics as independent variables and hospitalization or death as the dependent variable. RESULTS The analysis database consisted of 450,286 crash driver records, which linked to 4219 (0.9%) hospitalizations or deaths. There was an increasing trend for self-reported seatbelt use among crash-involved drivers from 80.5% in 1992 to 89.3% in 1997 (P<0.001). Police-reported alcohol intoxication among crash-involved drivers showed a decreasing trend from 2.4% in 1992 to 1.5% in 1997 (P<0.001). There was no trend for police-reported fatigue-related crashes. Odds ratios of hospitalization or death for seatbelt use, alcohol involvement, and fatigue were significant and did not fluctuate considerably between 1992 and 1997. Seatbelt use offered a protective effect from hospitalization or death, while alcohol intoxication and fatigue contributed to increased likelihood of hospitalization or death. CONCLUSIONS These results suggest that while some improvement has been made in decreasing seatbelt non-use and driver alcohol intoxication among crash-involved drivers, no improvement has been made in reducing fatigue-related crashes.