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Evaluating epidemiologic evidence of the effects of food and nutrient exposures.

The objective of this paper is to discuss some of the issues to be considered when evaluating and interpreting epidemiologic evidence from observational studies that collect data on dietary intake. The assessment of such evidence should include consideration of the study design, sample selection, and the measurements of exposure and disease. The degree and type of error in nutrient data can lead to analytic problems and potentially be a source of bias either toward or away from the null value. Because methods of statistical correction and adjustment for error, such as energy adjustment, cannot necessarily completely compensate for sources of bias in dietary data, additional research should be conducted on sources of error in dietary data. Published research using reported dietary data should include a discussion of potential sources of error and their effect on the results. The most useful studies are likely to be those designed to address a clearly defined prior hypothesis about a specific diet-disease relation. Because of the potential for bias and confounding, observational epidemiologic studies of diet and outcome cannot generally provide decisive evidence by themselves either for or against specific hypotheses. Although randomized clinical trials of the effects of specific nutrients or dietary modifications are not always feasible, they provide more definitive results and should generally be considered more valid than observational studies using self-reported dietary intake. Well-designed observational epidemiologic studies using self-reported dietary intake can provide valuable data to support or challenge hypotheses derived from clinical or laboratory data and to suggest further directions for investigation.

Bias↗

Asthma: an analysis of high-cost patients.

OBJECTIVE: To examine characteristics of asthma patients who accounted for 80 percent of national expenditures in 1994 dollars. STUDY DESIGN: Data were extracted from a comprehensive data source, the 1987 National Medical Expenditure Survey (NMES) of approximately 35,000 individuals. PATIENTS AND METHODS: Persons of interest were identified using any occurrence of the ICD-9 code 493 or subcategories. Population weighting factors were used to estimate the population in the United States who sought care for the treatment of asthma. Two groups were identified: a high-cost group, which accounted for 80 percent of the direct medical expenditures, and a low-cost group, which represented 20 percent of expenditures. All analyses were performed using SUDAAN software, which takes into account the complex sampling design used in NMES. RESULTS: Individuals who rated their health as poor or fair were more likely to be in the high-cost group, as compared with those who rated their health as good or excellent (p < .0009). Persons who reported having Medicare, other government, or private insurance were more likely to be in the high-cost group as compared to those with Medicaid and self-pay (p = .01). A person was more likely to be in the high-cost group if he or she used four or more different medications to treat asthma (p < .0001). CONCLUSIONS: Persons with asthma are more likely to have greater medical expenditures if they use four or more medications and have deteriorated health status. Managed care organizations and public programs may find these characteristics useful in targeting asthma prevention and management programs.

Anti-Asthmatic Agents↗

Methodological issues of an epidemiological study: from the results of a study on psychological problems seen in outpatients visiting the internal medicine departments of general hospitals.

The frequency and type of psychological problems of outpatients in general healthcare settings, the recognition and management of those problems by physicians, and the course of the problems were investigated using a two-stage sampling design method. The subjects were outpatients visiting the department of internal medicine of two general hospitals in Nagasaki prefecture. For the first-stage investigation, the General Health Questionnaire 12-item version (GHQ-12) was used. A second-stage investigation was then conducted, which used many instruments containing the Composite International Diagnostic Interview (CIDI) and Groningen Social Disability Scale (GSDS). As a result, 1555 patients participated in the first-stage, 483 were selected and 336 (69.5%) participated in the second-stage investigation. No significant differences were seen in age or sex between the GHQ score groups among the 1555 subjects of the core sample. The background factors of the two hospital samples differed significantly in the distribution of age, sex and physical diseases. There were some differences in the participation between men and women in age and GHQ score. It was then suggested that variances should be considered in such an epidemiological study.

Adolescent↗

Relative fitness and frailty of elderly men and women in developed countries and their relationship with mortality.

OBJECTIVES: To investigate the relationship between accumulated health-related problems (deficits), which define a frailty index in older adults, and mortality in population-based and clinical/institutional-based samples. DESIGN: Cross-sectional and cohort studies. SETTING: Seven population-based and four clinical/institutional surveys in four developed countries. PARTICIPANTS: Thirty-six thousand four hundred twenty-four people (58.5% women) aged 65 and older. MEASUREMENTS: A frailty index was constructed as a proportion of all potential deficits (symptoms, signs, laboratory abnormalities, disabilities) expressed in a given individual. Relative frailty is defined as a proportion of deficits greater than average for age. Measures of deficits differed across the countries but included common elements. RESULTS: In each country, community-dwelling elderly people accumulated deficits at about 3% per year. By contrast, people from clinical/institutional samples showed no relationship between frailty and age. Relative fitness/frailty in both sexes was highly correlated (correlation coefficient >0.95, P<.001) with mortality, although women, at any given age, were frailer and had lower mortality. On average, each unit increase in deficits increased by 4% the hazard rate for mortality (95% confidence interval=0.02-0.06). CONCLUSION: Relative fitness and frailty can be defined in relation to deficit accumulation. In population studies from developed countries, deficit accumulation is robustly associated with mortality and with age. In samples (e.g., clinical/institutional) in which most people are frail, there is no relationship with age, suggesting that there are maximal values of deficit accumulation beyond which survival is unlikely.

Age Distribution↗

Metabolic syndrome predicts mobility decline in a community-based sample of older adults.

OBJECTIVES: To determine whether metabolic syndrome is an independent predictor of decline in mobility in an elderly community sample. DESIGN: Biracial community-based prospective cohort study. SETTING: Urban and rural areas of central North Carolina. PARTICIPANTS: One thousand two hundred twenty-nine older African Americans and whites, mean age 77.0, who were participants in the Duke Established Populations for Epidemiologic Studies of the Elderly. MEASUREMENTS: Sociodemographic data and data on mobility (a subset of items from the Rosow-Breslau scale), depression (Center for Epidemiological Studies Depression Scale), self-report of medical conditions, body mass index, cognitive function (Short Portable Mental Status Questionnaire), blood pressure, height, and waist circumference. High-density lipoprotein cholesterol, triglycerides, and blood glucose were available from blood samples. Metabolic syndrome was calculated for subjects with complete data. RESULTS: Twenty-nine percent of the sample met criteria for metabolic syndrome. In bivariate analyses, age, sex, race, education, cognitive impairment, depression, impairment in mobility, history of stroke and heart disease, and metabolic syndrome at baseline were associated with a decline in mobility 4 years later. Regression analysis controlling for the above variables demonstrated that metabolic syndrome persisted as an independent and highly significant predictor of decline in mobility. CONCLUSION: These findings suggest that metabolic syndrome may be a distinct risk factor for mobility decline in community-dwelling older people.

Activities of Daily Living↗

Adolescent depressive disorder: a population-based study of ICD-10 symptoms.

OBJECTIVE: Earlier studies have suggested that symptoms of depressive disorder in adolescents may differ from those found in adults. Even so, diagnostic criteria developed in adults have come to be widely applied to younger subjects. This study examines the frequency of ICD-10 symptoms in depressive disorder and their association with severity in a large community sample of adolescents aged 15 to 18 years. METHOD: A six-wave prospective study of adolescent health and emotional wellbeing in 2032 Australian secondary school students provided an opportunity to conduct a two-phase study of adolescent onset depression. A self-administered computerised form of the revised Clinical Interview Schedule (CIS-R) was used as a first phase diagnostic measure. Second phase assessment using the Composite International Diagnostic Interview (CIDI) allowed the delineation of a group fulfilling criteria on both instruments. The ICD-10 symptoms and severity profiles for depression were generated with standard algorithms. RESULTS: 1947 (95.8%) out of 2032 subjects in the designated sample completed phase 1 assessment at least once. Participation rates at phase 2 interviews were 93%. Over the 30-month study period 69 subjects (10 male, 59 female) fulfilled criteria for ICD-10 depressive episodes on both the CIS-R and CIDI. Thirty-one per cent (n = 21) had experienced a severe episode, 46% (n = 32) moderate and 23% (n = 16) mild episodes. Loss of interest and pleasure, decreased energy and fatigue, sleep disturbance, suicidal ideation and diminished concentration most clearly distinguished adolescents with depressive disorder from controls. Self-reproach and guilt, psychomotor agitation and/or retardation and appetite disturbance with weight change showed the clearest increase in frequency with increasing severity of episode. The somatic syndrome was reported by close to one in three of those with a severe depressive episode, but was uncommon in those with mild and moderate episodes. CONCLUSIONS: The ICD-10 diagnostic criteria are applicable to depressive disorder in older adolescents. With the exception of depressed mood, found in one in five non-cases, all other symptoms were common in cases and uncommon in non-cases. Practitioner awareness of symptoms indicating the presence and severity of disorder should enhance early identification and choice of treatment in adolescent depression.

Adolescent↗

Early-season colonization patterns of the boll weevil (Coleoptera: Curculionidae) in Central Texas cotton.

It is commonly believed that colonization of early-season cotton, Gossypium hirsutum L., by overwintered boll weevils, Anthonomus grandis grandis Boheman, is concentrated on field margins. However, supporting experimental evidence is not available. In 1999 and 2000, we examined colonization patterns of overwintered boll weevils in Central Texas cotton on the bases of adult collections by a pneumatic sampler and hand collections of abscised infested squares. Samples were taken from sites arranged in a grid that extended inward >70 m from the field margin. Adults were collected from shortly after seedling emergence until the flowering stage, and infested squares were collected during the one-third grown square stage. Despite numerical trends, the numbers of adult weevils collected were not significantly different between years or sexes, or among plant phenological stages. Field-to-field variation among collections was considerable and likely prevented detection of differences among these factors. Spatial patterns represented by adult weevil and infested square collections were examined by logistic regressions fitted to the respective probabilities of weevil detection at each designated sample site. Although we observed trends for slightly decreased probability of weevil detection with increased distance from the field margin, these trends were too weak to be demonstrated statistically. Our results indicate the boll weevil does not consistently exhibit a strong edge-oriented colonization pattern, and that management tactics that are predicated on these patterns, such as border sprays, should be used with caution.

Animals↗

Fertilization and pregnancy outcome after intracytoplasmic injection with fresh or cryopreserved ejaculated spermatozoa.

OBJECTIVE: To assess fertilization, implantation, and pregnancy rates in patients undergoing ICSI using fresh and cryopreserved sperm from ejaculated semen samples. DESIGN: Retrospective study. SETTING: Academic and private medical centers. PATIENT(S): One hundred fifty-eight patients. INTERVENTION(S): Intracytoplasmic sperm injection. MAIN OUTCOME MEASURE(S): Fertilization, implantation, and pregnancy rates were evaluated; 61 cycles of ICSI were performed with cryopreserved and 79 cycles of ICSI were performed with fresh spermatozoa. Also, we divided the outcomes according to the semen characteristics, normozoospermia, oligozoospermia, asthenozoospermia, and oligoasthenozoospermia. RESULT(S): Overall, normal-fertilization rates were higher using fresh sperm (73.8%) compared with cryopreserved sperm (68.7%). Cycles performed in patients with normozoospermia or oligozoospermia had similar fertilization, implantation, and pregnancy rates using fresh or cryopreserved sperm. When asthenozoospermic and oligoasthenozoospermic semen samples were used, the normal-fertilization rate was higher with fresh sperm compared with cryopreserved sperm. However, implantation and pregnancy rates were similar in fresh and cryopreserved sperm samples from patients with asthenozoospermia or oligoasthenozoospermia. CONCLUSION(S): Semen with abnormalities in the motility may be more susceptible to sperm cryopreservation damage, resulting in lower fertilization rates. However, once the oocyte is fertilized, implantation and pregnancy rates are similar to those in patients with oligozoospermia and normozoospermia.

Adult↗

Inadequate therapy for asthma among children in the United States.

OBJECTIVE: Childhood asthma morbidity and mortality are increasing despite improvements in asthma therapy. We hypothesized that a substantial number of children with moderate to severe asthma are not taking the maintenance medications recommended by national guidelines. The objective of this study was to describe medication use among US children with asthma and determine risk factors for inadequate therapy. METHODS: The National Health and Nutrition Examination Survey (NHANES) III 1988-1994 provided cross-sectional, parent-reported data for children 2 months to 16 years of age. Analysis focused on children with moderate to severe asthma (defined as having any hospitalization for wheezing, >/=2 acute visits for wheezing, or >/=3 episodes of wheezing over the past year). We defined these children as adequately treated if they had taken a maintenance medication (inhaled corticosteroid, cromolyn, or theophylline) during the past month. Demographic variables were analyzed for independent associations with inadequacy of therapy. The statistical analysis used SUDAAN software to account for the complex sampling design. RESULTS: A total of 1025 children (9.4%) had physician-diagnosed asthma. Of those with moderate to severe asthma (n = 524), only 26% had taken a maintenance medication during the past month. Even among children with 2 or more hospitalizations over the previous year, only 32% had taken maintenance medications. In a logistic regression analysis, factors significantly associated with inadequate therapy included: age </=5 years, Medicaid insurance, and Spanish language. Children surveyed after 1991, when national guidelines for asthma management became available, were no more likely to have taken maintenance medications than children surveyed before 1991. CONCLUSION: Most children with moderate to severe asthma in this nationally representative sample, including those with multiple hospitalizations, did not receive adequate asthma therapy. These children may incur avoidable morbidity. Young children, poor children, and children from Spanish-speaking families appear to be at particularly high risk for inadequate therapy.

Asthma↗

Examining neighbourhood confounding in a survey: an example using the National Health and Nutrition Examination Survey II.

This paper demonstrates a methodology for examining whether neighbourhood stratification lessens the confounding bias of some specific risk-factor/disease associations in analysis of the National Health and Nutrition Examination Survey II (NHANES II). The fortuitous clustering of the sample design of NHANES allows us to estimate risk-factor/disease associations with and without controlling for neighbourhood effects on the same population. We briefly discuss the implications of this methodology for neighbourhood matching in case-control studies.

Adolescent↗

In vitro and in vivo (cyto)toxicity assays using PVC and LDPE as model materials.

The choice for a biomaterial is partly based on the outcome of (cyto)toxicity assays. The rationales behind the selection of certain parameters, such as cell lines, controls, and animals, were evaluated using a positive and a negative control, and one experimental sample designed to induce intermediate toxicity. Extraction and direct contact assays were performed using human epidermal keratinocytes and mouse fibroblasts and mouse epithelial cells. Cell survival was measured with the tetrazolium salt (MTT) reduction assay. In addition, local implantation studies were performed in mice and rats. The positive control induced a high degree of toxicity in all in vitro tests performed, indicating that the toxicity observed in the direct contact assay was due to in situ extraction of toxic components. In the direct contact assay the negative control tested on the mouse fibroblasts resulted in a significant reduction of cell survival. No decrease in cell survival was found using the experimental sample. Subcutaneous implantation studies in mice showed that the positive control material induced a severe degeneration in mice. However, in rats just minimal alterations were noted. The experimental material induced moderate responses only in mice. Our results indicate that the direct contact assay provides limited additional information on the cytotoxicity of materials if certain limitations are not taken into account. For the in vivo implantation assay mice were superior to rats in detecting local toxic responses.

Animals↗

The chi-square test: its use in rehabilitation research.

OBJECTIVE: This report examines the impact of collecting and analyzing sequential data from the same sample using the chi-square test. Researchers in rehabilitation frequently analyze categorical data collected repeatedly from the same sample. DESIGN: Simulations were conducted using the chi-square test to analyze data with correlations between pretest and posttest ranging from .20 to .80. The simulations were analyzed using the standard chi-square based on a 2 x 2 contingency table. RESULTS: An incidence of type 1 errors of approximately .30 for an expected alpha of .05 was found when the correlation (serial dependence) between pretest and posttest was high (phi = .80). For simulations using an alpha = .01, the type 1 error rate was .18 for data with substantial correlation (phi = .80). CONCLUSION: Rehabilitation researchers who use the chi-square test with data collected repeatedly from the same sample risk committing a type 1 error and misinterpreting their results. Alternatives to the standard chi-square test, such as McNemar's test, should be considered when correlated data are analyzed using a 2 x 2 contingency table.

Chi-Square Distribution↗

Method for efficient storage and transportation of sputum specimens for molecular testing of tuberculosis.

SETTING: The polymerase chain reaction (PCR) is a highly sensitive method for the detection of Mycobacterium tuberculosis and is available in most countries, though to a lesser extent in rural areas. OBJECTIVE: To amplify M. tuberculosis DNA sequences of sputum spotted on FTA cards and compare them with the results of microscopic examination among culture-positive samples. DESIGN: A total of 102 sputum specimens of TB patients in treatment were spotted on FTA cards and stored at room temperature until DNA analysis. We assessed the IS6110 region of M. tuberculosis. The efficacy of the PCR assay for the direct detection of M. tuberculosis was evaluated and compared with the results of cultures (Middlebrook 7H9 broth) and smears of fresh sputum specimens. RESULTS: We were able to detect 10 fg/microl of mycobacterial DNA even after 6 months in storage. The PCR sensitivity and specificity using the FTA card system were 82% and 96%, while microscopic examination showed 41% and 95%, respectively. CONCLUSION: The FTA card system for the storage of bacterial DNA from sputum samples should be considered for the molecular diagnosis of tuberculosis. Samples can easily be obtained from geographically isolated populations and shipped by mail for accurate molecular diagnosis.

Bacteriological Techniques↗

A beginner's guide to research.

The purpose of this article is to provide an overview of the research process and highlight some of the most important aspects. The definition of research and some general terminology are reviewed. Included in this article are discussions of the following: defining a problem, reviewing the literature, types of study designs, sampling, types of measurement, reliability and validity, limitations and assumptions, data analysis, ethical concerns with human subjects, and time management. Examples of published research are used to illustrate the points where necessary. A supplemental bibliography is provided to direct the interested reader to more in-depth discussions of the various aspects of the research process.

Data Interpretation, Statistical↗

Common errors and controversies in pharmacoeconomic analyses.

The need to demonstrate the cost effectiveness of healthcare interventions has led to a rapid increase in the use of economic tools within pharmaceutical evaluations. Pharmacoeconomics is employed at many stages of the evaluation process, helping to predict which products are likely to be economically viable at an early stage, and providing information to aid price and reimbursement negotiations as well as formulary and purchasing decisions in conjunction with phase III and IV clinical trials. The ability of economic evaluations to accurately determine the best use of society's scarce resources, however, is strongly influenced by the existence of areas of confusion, controversy and dispute which hinder the researcher at every step. A good economic evaluation requires a number of ingredients including: (i) relevant, good quality clinical data, raising issues of trial design, sample size and perspective; (ii) relevant costs and outcomes, measured, valued and discounted credibly and accurately; (iii) appropriate methods of data analysis (statistical, incremental and sensitivity); and, once the trial is over, (iv) presentation of the results in a way which maximises the generalisability of the results and, hence, the usefulness of the research. None of these areas are trouble-free but with understanding and openness, mistakes can be minimised.

Drug Costs↗

Nursing research in Ireland.

This review presents an analysis of research published by Irish nurses during the period 1990-2005. The analysis is the first effort made to identify the main characteristics of Irish nursing research. Overall, 213 published studies were identified for consideration, from which, 152 were included in the review. The studies were published in 60 journals, 4 books, and 8 research reports. Journal articles selected from 6 journals accounted for 52%. Inclusion criteria were quality of research design, sampling (including sample size), data analysis, scientific merit, and authorship. Each article was analyzed based on this schema. The major areas of research identified included clinical practice (56%) (e.g., medical surgical, mental health, intellectual disability, and maternal and child), nursing management and professional issues (19%), and nursing education (25%).

Authorship↗

Foreign-born emigration: a new approach and estimates based on matched CPS files.

The utility of postcensal population estimates depends on the adequate measurement of four major components of demographic change: fertility, mortality, immigration, and emigration. Of the four components, emigration, especially of the foreign-born, has proved the most difficult to gauge. Without "direct" methods (i.e., methods identifying who emigrates and when), demographers have relied on indirect approaches, such as residual methods. Residual estimates, however are sensitive to inaccuracies in their constituent parts and are particularly ill-suited for measuring the emigration of recent arrivals. Here we introduce a new method for estimating foreign-born emigration that takes advantage of the sample design of the Current Population Survey (CPS): repeated interviews of persons in the same housing units over a period of 16 months. Individuals appearing in a first March Supplement to the CPS but not the next include those who died in the intervening year, those who moved within the country, and those who emigrated. We use statistical methods to estimate the proportion of emigrants among those not present in the follow-up interview. Our method produces emigration estimates that are comparable to those from residual methods in the case of longer-term residents (immigrants who arrived more than 10 years ago), but yields higher--and what appear to be more accurate--estimates for recent arrivals. Although somewhat constrained by sample size, we also generate estimates by age, sex, region of birth, and duration of residence in the United States.

Adolescent↗

Transmission of methicillin-resistant Staphylococcus aureus to preterm infants through breast milk.

OBJECTIVE: To determine a potential source of MRSA colonization and infection among preterm infants in a neonatal intensive care unit (NICU) using molecular analysis of breast milk samples. DESIGN: Case report, outbreak investigation. RESULTS: Preterm triplets were delivered at 26 weeks' gestation via cesarean section when routine active surveillance for MRSA was performed for all infants in a NICU. Surveillance consisted of swabbing the throat, nose, and umbilicus (TNU) weekly. Although infants A and B initially had negative TNU swabs, repeat cultures were positive for MRSA on day of life (DOL) 10 and DOL 18, respectively. Surveillance and clinical cultures for infant C were negative. Infant A developed sepsis, and multiple blood cultures were positive for MRSA beginning on DOL 14. Infant B developed conjunctivitis and a conjunctival exudate culture was positive for MRSA on DOL 70. Both infants were fed breast milk via nasogastric tube. Cultures of breast milk samples for infants A and B dated prior to either infant's first positive surveillance culture were positive for MRSA. All MRSA isolates had identical results on antibiotic susceptibility testing. PFGE demonstrated identical banding patterns for the MRSA isolates from the blood culture of infant A, breast milk for infants A and B, and a surveillance swab from infant B. At no time did the mother develop evidence of mastitis or other local breast infection. CONCLUSIONS: MRSA can be passed from mother to preterm infant through contaminated breast milk, even in the absence of maternal infection. Colonization and clinical disease can result.

Chicago↗