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Biomedical subjects

S R Cole

Publications and source records attributed to S R Cole.

At least 19 recordsLinked to original sources

Participation in screening for colorectal cancer based on a faecal occult blood test is improved by endorsement by the primary care practitioner.

OBJECTIVES: To investigate the influence of general practitioner (GP) endorsement on participation in screening for colorectal cancer based on a faecal occult blood test (FOBT). SETTING: South Australian residents (n=2400), in 1999, aged >50 years. METHODS: Random selection of three groups (GP1, GP2, GP3) from two general practices and of one group (ER) from the federal electoral roll; n=600 per group. Without previous communication or publicity, subjects were posted an offer of screening by immunochemical FOBT. The GP1 and ER groups were invited without indication that their GP was involved; GP2 received an invitation indicating support from the practice; and GP3 received an invitation on practice letterhead and signed by a practice partner. A reminder was posted at 6 weeks. Participation was defined as return of correctly completed FOBT sample cards within 12 weeks. RESULTS: Participation rates were: GP1 192/600 (32.0%), GP2 228/600 (38.0%), and GP3 244/600 (40.7%); chi(2)=10.2, p=0.006. Both GP2 and GP3 differed significantly from GP1 (odds ratio (OR) 0.77, 95% confidence interval (95% CI) 0.60 to 0.98 and relative risk (RR)=0.69, 95% CI 0.54 to 0.87 respectively). ER (193/600 (32.2%)) and GP1 were not significantly different. Age but not sex was significantly associated with participation. Overall test positivity rate was 4.6%; five malignancies were found in the 918 who performed FOBT. CONCLUSIONS: Association of a GP of recent contact with a screening offer in the form of a personalised letter of invitation achieves better participation than does the same letter from a centralised screening unit that does not mention the GP. Thus, GP enhanced participation is achievable without their actual involvement. Additional strategies are needed to further improve participation.

Age Factors↗

Effect of dietary restriction on participation in faecal occult blood test screening for colorectal cancer.

OBJECTIVES: To determine if participation in colorectal cancer screening using faecal occult blood testing (FOBT) is affected by a restrictive diet and if it is associated with certain demographic variables. PARTICIPANTS AND SETTING: 1,203 residents of South Australia aged 50-69 years, with no "currently active bowel disease", randomly selected from a database of people willing to be contacted about unspecified health issues. DESIGN: Randomised controlled trial: participants were offered screening by immunochemical FOBT by mail in 1998. Half were randomly allocated to a group instructed to follow a low-peroxidase diet, as required for guaiac FOBT, while the other group was not so restricted. MAIN OUTCOME MEASURES: Effect of diet restriction on participation (return of correctly completed FOBT sample cards within 15 weeks); time taken to return cards; relationships between participation and demographic variables. RESULTS: Participation rates were 65.9% (no-diet group) and 53.3% (diet group) (difference, 12.6%; 95% CI, 7.1%-18.1%). In the first week, rates of return as a proportion of all tests returned were 13.1% (no-diet) and 1.6% (diet) (difference, 11.5%; 95% CI, 8.6%-14.4%), increasing to 54.3% and 44.5%, respectively, after five weeks (difference, 9.8%; 95% CI, 4.2%-15.4%). Participation was significantly associated with older age (odds ratio, 1.40; 95% CI, 1.10-1.78), but not sex, Index of Social Disadvantage or rural versus urban address. CONCLUSIONS: Dietary restrictions create a barrier to FOBT-based screening for colorectal cancer. The use of immunochemical rather than guaiac FOBT removes this barrier.

Aged↗

Isolation of the components of a complex mixture by means of column switching for their enhanced detection by mass spectrometry.

Mass spectral characterization of low-level impurities in drug substances and formulations may be challenging when using a validated HPLC method developed for optimal chromatographic performance. In many cases, either the mobile phase contains non-volatile additives that are deleterious to the operation of the mass spectrometer, or some of the related substances fail to ionize effectively under electrospray ionization or atmospheric pressure chemical ionization conditions. This paper describes a way to capture these low-level compounds from an analytical HPLC column using a small trapping column. Mixture components are retained on the trapping column by means of reducing the solvent strength of the eluent. Subsequent elution of trapped compounds using mobile phases more amenable to mass spectral analysis yields improved detection and characterization of low-level compounds of interest. Possible applications of peak trapping and elution include: (1) analysis of compounds separated using a mobile phase containing high concentrations of non-volatile additives, (2) analysis of organic acids separated using a low-pH mobile phase (containing trifluoroacetic acid), and (3) improving the detection limit of a low-level compound of interest through multiple collections. The peak trapping apparatus and optimization experiments are described.

Chromatography, High Pressure Liquid↗

Analysis of complex survey data using SAS.

Commonly used statistical methods and software packages typically assume that observations are independent and identically distributed and fail to account for complex sampling designs when present. I suggest an approach to analyzing complex survey data in SAS, using weighted generalized estimating equations. Limited Monte Carlo simulations support the method. An example demonstrates application of the method and compares results to those from software commonly used in the analysis of complex survey data.

Aged↗

Recall bias in a prospective cohort study of acute time-varying exposures: example from the herpetic eye disease study.

Recall bias is possible in a prospective cohort study when exposure status is transient and must be periodically recalled, and ascertainment occurs after symptom onset. We know of no published demonstration of such bias at play in a prospective cohort study. In a substudy of a randomized clinical trial, 308 participants were prospectively followed to investigate potential acute triggers of ocular herpes simplex virus (HSV) recurrences. Participants reported on the presence of systemic infection or high psychological stress (exposures) on a home log that was completed weekly for up to 15 months and mailed to the study's coordinating centers. By protocol, exposure reporting was to occur on the last day of the week (Sunday) so that a prospective 1-week lag period between exposure and outcome in the following week could be assessed. The study outcome was development of a recurrence of ocular HSV disease documented by clinical examination. Using 35 weekly reports of exposure properly completed before the week of an outcome, there was no evidence of higher risk of HSV recurrence associated with systemic infection (rate ratio = 0.62, 95% confidence interval [CI]: 0.19-2.02) or high psychological stress rate (ratio = 0.0, 95% CI: 0.0-undefined). In contrast, when the analysis was based on 26 weekly reports of exposure improperly completed on or after the date of outcome, the risk of recurrence associated with systemic infection was estimated to be 4-fold (rate ratio = 4.07, 95% CI: 1.84-8.98), and there was a suggestion of a 2-fold risk associated with high psychological stress (rate ratio = 2.02, 95% CI: 0.69-5.91). Without real-time monitoring of exposure reporting, preservation of the temporal exposure-disease relationship-an implicit assumption of the prospective cohort study design-may be particularly tenuous when transient exposures are investigated longitudinally.

Bias↗

The Amblyopia Treatment Index.

OBJECTIVE: To develop a questionnaire to assess the acceptability of amblyopia treatment and its effect on the child and family. METHODS: A 20-item parental survey was developed and pilot tested on 64 subjects, aged 3 to 6 years, participating in the Amblyopia Treatment Study, a randomized trial comparing patching and atropine as treatments for moderate amblyopia. The survey was administered after 4 weeks of treatment. A descriptive item analysis and an internal consistency reliability analysis were performed. RESULTS: Nineteen of the 20 items demonstrated adequate variability as evidenced by the frequency distributions for item responses. Only 4 (<1%) of 1280 possible item responses were missing, one each by 4 different respondents. Factor analysis identified 3 treatment-related factors--"adverse effects," "compliance," and "social stigma"--among 11 of the 20 items. The internal-consistency reliability alpha for the 5-item adverse effects subscale was 0.82, the 4-item compliance subscale alpha was 0.81, and the 2-item social stigma subscale alpha was 0.84. CONCLUSIONS: The Amblyopia Treatment Index appears to be a useful instrument for assessing the impact of amblyopia treatment in 3- to 6-year-old children.

Amblyopia↗

Intake of vegetables rich in carotenoids and risk of coronary heart disease in men: The Physicians' Health Study.

BACKGROUND: Previous studies of diet and coronary heart disease (CHD) have focused on intake of nutrients rather than whole foods. Because of the findings that dietary fibre, folate and antioxidants may be protective for CHD, increased intake of vegetables has been recommended. However, due to the chemical and physical complexity of vegetables, the effects of individual nutrients may differ if eaten as whole foods. Moreover, little is known about the direct association between vegetable intake and risk of CHD. METHODS: We prospectively evaluated the relation between vegetable intake and CHD risk in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among 22 071 US male physicians aged 40-84 years in 1982. In this analysis, we included 15 220 men without heart disease, stroke or cancer at baseline who provided information on their vegetable intake at baseline, and in the 2nd, 4th and 6th years of follow-up using a simple semiquantitative food frequency questionnaire including eight vegetables. We confirmed 1148 incident cases of CHD (387 incident cases of myocardial infarction and 761 incident cases of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) during 12 years of follow-up. RESULTS: After adjusting for age, randomized treatment, body mass index (BMI), smoking, alcohol intake, physical activity, history of diabetes, history of hypertension, history of high cholesterol, and use of multivitamins, men who consumed at least 2.5 servings/day of vegetables had a relative risk (RR) of 0.77 (95% CI : 0.60-0.98) for CHD, compared with men in the lowest category (<1 serving/day). Adjusting for the same covariates in an analysis of the overall trend that considered intake of vegetables as a continuous variable, we found a RR of 0.83 (95% CI : 0.71-0.98) for risk of CHD for each additional serving/day of vegetables. The inverse relation between vegetable intake and CHD risk was more evident among men with a BMI > or =25 (RR = 0.71, 95% CI : 0.51-0.99) or current smokers (RR = 0.40, 95% CI : 0.18-0.86) comparing highest to the lowest categories of intake. CONCLUSIONS: Our results suggest an inverse association between vegetable intake and risk of CHD. These prospective data support current dietary guidelines to increase vegetable intake for the prevention of CHD.

Adult↗

Time urgency and risk of non-fatal myocardial infarction.

BACKGROUND: Inconsistencies in the literature linking Type A behaviour pattern (TAB) to coronary heart disease (CHD) may be due to differences in the effects of various components of TAB, namely aggressiveness, hostility, ambitiousness, competitive drive, and a chronic sense of time urgency. METHODS: We investigated the association between sense of time urgency/impatience and non-fatal myocardial infarction (MI) in a study of 340 cases and an equal number of age-, sex-, and community-matched controls. RESULTS: A dose-response relation was apparent among subjects who rated themselves higher on the four-item time urgency/impatience scale (P-value for trend <0.001), with a matched odds ratio (OR) for non-fatal MI of 4.45 (95% CI : 2.20-8.99) comparing those with the highest rating to those with the lowest. After further adjustment for family history of premature MI, physical activity, body mass index, occupation, cigarette smoking, total caloric intake, per cent calories from saturated fat, alcohol intake, lipid levels, treated hypertension and diabetes, the dose-response relation remained (P-value for trend = 0.015) and the adjusted OR for MI was 3.99 (95% CI : 1.32-12.0) comparing those with the highest rating to those with the lowest. CONCLUSION: In these data, a sense of time urgency/impatience was associated with a dose-response increase in risk of non-fatal MI, independent of other risk factors. Prospective cohort studies of time urgency/impatience and incident CHD events are needed to confirm or refute these observations from a case-control study.

Adult↗

Regression models for unconstrained, partially or fully constrained continuation odds ratios.

Epidemiologists frequently encounter studies with ordered responses. Standard ordered response logit models, such as the continuation ratio model, constrain exposure to have a homogeneous effect across thresholds of the ordered response. We demonstrate a method for fitting regression models for unconstrained, partially or fully constrained continuation odds ratios using a 'person-threshold' data set. For each subject, we create a separate record for each response threshold the subject is 'at risk' of passing and then apply standard binary logistic regression to estimate the continuation-ratio model. An example demonstrates the unconstrained, partially and fully constrained continuation-ratio model, while a small simulation study examines some properties of the proposed 'person-threshold' approach. Finally, we present a brief discussion of statistical software to implement the method.

Epidemiologic Methods↗

Interaction between HLA-DR2 and abnormal brain MRI in optic neuritis and early MS. Optic Neuritis Study Group.

The association of the human leukocyte antigen (HLA)-DR2 allele with brain MRI signal abnormalities and with the development of MS was assessed in 178 patients enrolled in the Optic Neuritis Treatment Trial. HLA haplotype DR2 was present in 85 (48%) of the 178 patients. Its presence was associated with increased odds of probable or definite MS at 5 years (odds ratio, 1.92; 95% confidence interval, 1.01 to 3.67; p = 0.04). The association was most apparent among patients with signal abnormalities on baseline brain MRI.

Administration, Oral↗

Test of item-response bias in the CES-D scale. experience from the New Haven EPESE study.

We present results of item-response bias analyses of the exogenous variables age, gender, and race for all items from the Center for Epidemiologic Studies Depression (CES-D) scale using data (N = 2340) from the New Haven component of the Established Populations for Epidemiologic Studies of the Elderly (EPESE). The proportional odds of blacks responding higher on the CES-D items "people are unfriendly" and "people dislike me" were 2.29 (95% confidence interval: 1.74, 3.02) and 2.96 (95% confidence interval: 2.15, 4.07) times that of whites matched on overall depressive symptoms, respectively. In addition, the proportional odds of women responding higher on the CES-D item "crying spells" were 2.14 (95% confidence interval: 1.60, 2.82) times that of men matched on overall depressive symptoms. Our data indicate the CES-D would have greater validity among this diverse group of older men and women after removal of the crying item and two interpersonal items.

Black or African American↗

Fruit and vegetable intake and risk of cardiovascular disease: the Women's Health Study.

BACKGROUND: Prospective data relating fruit and vegetable intake to cardiovascular disease (CVD) risk are sparse, particularly for women. OBJECTIVE: In a large, prospective cohort of women, we examined the hypothesis that higher fruit and vegetable intake reduces CVD risk. DESIGN: In 1993 we assessed fruit and vegetable intake among 39876 female health professionals with no previous history of CVD or cancer by use of a detailed food-frequency questionnaire. We subsequently followed these women for an average of 5 y for incidence of nonfatal myocardial infarction (MI), stroke, percutaneous transluminal coronary angioplasty, coronary artery bypass graft, or death due to CVD. RESULTS: During 195647 person-years of follow-up, we documented 418 incident cases of CVD including 126 MIs. After adjustment for age, randomized treatment status, and smoking, we observed a significant inverse association between fruit and vegetable intake and CVD risk. For increasing quintiles of total fruit and vegetable intake (median servings/d: 2. 6, 4.1, 5.5, 7.1, and 10.2), the corresponding relative risks (RRs) were 1.0 (reference), 0.78, 0.72, 0.68, and 0.68 (95% CI comparing the 2 extreme quintiles: 0.51, 0.92; P: for trend = 0.01). An inverse, though not statistically significant, trend remained after additional adjustment for other known CVD risk factors, with RRs of 1.0, 0.75, 0.83, 0.80, and 0.85 (95% CI for extreme quintiles: 0.61, 1.17). After excluding participants with a self-reported history of diabetes, hypertension, or high cholesterol at baseline, the multivariate-adjusted RR was 0.45 when extreme quintiles were compared (95% CI: 0.22, 0.91; P: for trend = 0.09). Higher fruit and vegetable intake was also associated with a lower risk of MI, with an adjusted RR of 0.62 for extreme quintiles (95% CI: 0.37, 1.04; P: for trend = 0.07). CONCLUSION: These data suggest that higher intake of fruit and vegetables may be protective against CVD and support current dietary guidelines to increase fruit and vegetable intake.

Age Factors↗

Effects of mutant c-kit in early myeloid cells.

Activating mutations in c-Kit, the receptor for Stem Cell Factor (SCF), have been identified in dysplasias and leukaemias of the mast cell lineage and have been shown to contribute to transformation in model systems. Early myeloid cells also normally express c-Kit and their survival, proliferation and differentiation is promoted by SCF. It might therefore be expected that c-Kit mutations could also be involved in some acute and/or chronic myeloid leukaemias. We have found that mutant c-Kit (and normal c-Kit in the presence of SCF) provides a strong differentiation stimulus in normal and immortalised murine early myeloid cells. Since maturation of haemopoietic cells, with the exception of mast cells, results in down-regulation of c-Kit expression, the transforming effects of mutant receptor may be self-limiting in most lineages. This is consistent with the observation that multipotential progenitor cells from some patients with systemic mastocytosis express mutant c-Kit. However, c-Kit mutations have been observed in a few cases of myelodysplastic syndromes or AML without mast cell features. Oncogenesis involves multiple genetic changes and the phenotype of malignant haemopoietic cells expressing mutant c-Kit may be influenced by co-oncogenic events. For example mutations blocking the differentiative effect of mutant c-Kit might result in AML rather than mastocytosis. Thus the extent to which c-Kit mutations contribute to malignancies of early myeloid phenotype remains unknown, and resolution of this issue is complicated by the heterogeneity of this family of diseases.

Animals↗

Amyloid goiter with parathyroid involvement: a case report and review of the literature.

Although involvement of the thyroid gland by amyloid is a relatively common phenomenon, diffuse enlargement of the gland secondary to infiltration by amyloid is infrequent. We report the pathologic findings in a case of primary amyloid goiter with involvement of a parathyroid gland in an euthyroid patient who presented to his physician with an enlarged thyroid, upper airway obstructive symptoms, and dysphagia. The clinical features of amyloid goiter, including difficulties in preoperative diagnosis and management, are discussed.

Adult↗

The National Eye Institute Visual Function Questionnaire: experience of the ONTT. Optic Neuritis Treatment Trial.

PURPOSE: To describe the health-related quality of life, measured with the National Eye Institute Visual Function Questionnaire (NEI-VFQ), of patients several years after the onset of optic neuritis, according to their neurologic and visual status; to assess the relationship between the NEI-VFQ subscales and clinical measures of visual function; and to assess the internal consistency reliability of the NEI-VFQ subscales. METHODS: The NEI-VFQ was administered to 244 patients 5 to 8 years after treatment for an episode of acute optic neuritis as part of the Optic Neuritis Treatment Trial. Visual acuity, visual field, contrast sensitivity, and color vision were measured at the same time as questionnaire completion. RESULTS: The NEI-VFQ scores generally were lower than those reported for a disease-free group. Reported dysfunction was greater when multiple sclerosis was present and when visual acuity was abnormal, supporting the construct validity of the NEI-VFQ. Rank correlations between the NEI-VFQ subscales and clinical measures of visual function were moderate at best. Internal consistency reliability was generally high for most of the NEI-VFQ subscales. CONCLUSIONS: These findings add support to the use of the NEI-VFQ as a valuable measure of self-reported visual impairment.

Acute Disease↗

Sense of exhaustion and coronary heart disease among college alumni.

Vital exhaustion, defined as a combination of fatigue, lack of energy, feelings of hopelessness, loss of libido, and increased irritability, has been proposed as a risk indicator for the development of coronary heart disease (CHD). It is unclear if the association between vital exhaustion and CHD is independent of sleep behavior, depression, and physical activity. We ascertained sense of exhaustion among 5,053 male college alumni who were free of cardiovascular disease, cancer, and chronic obstructive pulmonary disease by asking, "How often do you experience sense of exhaustion (except after exercise)?" on a health survey in 1980. Eight hundred fifteen men died during 12 years of follow-up, 25% due to CHD. After adjustment for age, body mass index, smoking status, and history of physician-diagnosed diabetes and hypertension, frequent sense of exhaustion was associated with a twofold increase in CHD mortality (rate ratio 2.07; 95% confidence interval 1.08 to 3.96). After additional adjustment for insomnia, sleep duration, use of sleeping pills and tranquilizers, physical activity, history of physician-diagnosed depression, and alcohol intake, the rate ratio was not appreciably altered; however, the association now was of borderline significance (rate ratio 2.06; 95% confidence interval: 0.98 to 4.36) because there were only 10 deaths from CHD among men who were frequently exhausted. In a prospective observational study, frequent sense of exhaustion appeared to be independently associated with increased risk of CHD mortality in men.

Adult↗

Insomnia and heart disease: a review of epidemiologic studies.

Since the discovery and successful treatment of sleep apnea, researchers seem to believe that the association between sleep disturbance and coronary heart disease (CHD) has been explained. To determine whether subjective nighttime sleep complaints (trouble sleeping, trouble falling asleep, trouble staying asleep), exclusive of apnea, predicted myocardial infarction and other coronary events, a MEDLINE search was conducted for articles published between January 1976 through August 1997. Ten studies with an explicit measure of association between an insomniac complaint and CHD were identified. Reported risk ratios for various sleep complaints and CHD events ranged from 1.0 for waking too early and CHD death in an elderly North Carolina community to 8.0 for the highest versus lowest quintile of a sleep scale in Finnish men. Higher quality studies showed risk ratios of 1.47-3.90 between trouble falling asleep and coronary events after adjusting for age and various coronary risk factors (combined effect=1.7, p<0.0001). While alternative explanations such as medication use still need to be ruled out, we theorize that a subjective insomniac complaint either may be part of a larger syndrome that includes poor health and depression, or it may be related to continual stressors, reduced slow-wave sleep, and autonomic dysfunction, which increase the risk of heart problems.

Confounding Factors, Epidemiologic↗

Simple bootstrap statistical inference using the SAS system.

Nonparametric bootstrap statistical inference is a robust computer intensive method for generating estimates of statistical variability for which formulae are not known or asymptotic assumptions are not met. A SAS macro that implements simple nonparametric bootstrap statistical inference is presented with an example. The program code is easily generalized to any SAS procedure which includes a BY statement, and to cases of clustered data.

Data Interpretation, Statistical↗