The Effect of a Regimen of Antifungal Cream Use on Episodes of Acute Adenolymphangitis (ADL) among Lymphedema Patients: An Application Using Marginal Structural Models.

Episodes of adenolymphangitis (ADL) are a recurrent clinical aspect of lymphatic filariasis (LF) and a risk factor for progression of lymphedema. Inter-digital entry lesions, often found on the web spaces between the toes of those suffering from lymphedema, have been shown to contribute to the occurrence of ADL episodes. Use of antifungal cream on lesions is often promoted as a critical component of lymphedema management. Our objective was to estimate the observed effect of antifungal cream use on ADL episodes according to treatment regimen among a cohort of lymphedema patients enrolled in a morbidity management program. We estimated this effect using marginal structural models for time varying confounding. In this longitudinal study, we estimate that for every one-unit increase in the number of times one was compliant to cream use through 12 months, there was a 23% (RR = 0.77 (0.62, 0.96)) decrease in the number of ADL episodes at 18 months, however the RR's were not statistically significant at other study time points. Traditionally adjusted models produced a non-significant RR closer to the null at all time points. This is the first study to estimate the effect of a regimen of antifungal cream on the frequency of ADL episodes. This study also highlights the importance of the consideration and proper handling of time-varying confounders in longitudinal observational studies.

Longitudinal analysis of community health workers' adherence to treatment guidelines, Siaya, Kenya, 1997-2002.

OBJECTIVES: To investigate community health workers' (CHW) adherence over time to guidelines for treating ill children and to assess the effect of refresher training on adherence. METHODS: Analysis of 7151 ill-child consultations performed by 114 CHWs in their communities from March 1997-May 2002. Adherence was assessed with a score (percentage of recommended treatments that were prescribed), calculated for each consultation. Recommended treatments were those that were indicated based on CHW assessments. We used piecewise regression models to evaluate adherence before and after training. RESULTS: The average adherence score was 79.4%. Multivariable analyses indicate that immediately after the first refresher training, the mean adherence level improved for patients with a severe illness, but worsened for patients without severe illness. Adherence scores declined rapidly during the 6 months after the second refresher training. CONCLUSIONS: The first refresher was partially effective, the second refresher had an effect contrary to that intended, and patient characteristics had a strong influence on adherence patterns. Longitudinal studies are useful for monitoring the dynamics of CHW performance and evaluating effects of quality improvement interventions.

The influence of observation and setting on community health workers' practices.

OBJECTIVE: To determine whether results from an evaluation that involved observation of community health workers while they performed patient consultations in a hospital reflected normal everyday practices. DESIGN: Comparison of two samples of ill-child consultations: (i) consultations performed during an evaluation in which we observed community health workers in a hospital in-patient and outpatient department from February to March 2001 and (ii) consultations performed under no observation in villages and documented in clinical registers within the 90 days before the hospital evaluation. SETTING: Siaya District Hospital and villages in Kenya. STUDY PARTICIPANTS: Community health workers. MAIN OUTCOME MEASURE: Treatment error indicator, defined as the percentage of consultations where at least one recommended treatment (where recommended treatments were those that were indicated based on community health worker assessments of the child's condition) was not prescribed. RESULTS: We analyzed data on 1132 consultations (372 from the hospital evaluation and 760 from the community) performed by 103 community health workers. For all types of consultations combined, the difference between treatment error indicators (hospital minus community) was -16.4 [95% confidence interval (CI): -25.6, -7.1]. CONCLUSIONS: We found that community health workers made treatment errors less frequently when they were observed in a hospital in-patient or outpatient department than when they were not observed in the community. Evaluations that involve the observation of community health workers in a hospital setting might overestimate the quality of care that they normally give in their villages.

Depressive symptoms during childhood and adult obesity: the Zurich Cohort Study.

Depression and obesity have become major health problems with increasing prevalence. Given the limited effectiveness of treatment for weight problems, the identification of novel, potentially modifiable risk factors may provide insights on new preventive approaches to obesity. The purpose of this study was to test the hypothesis that depressive symptoms during childhood are associated with weight gain and obesity during young adulthood. Participants were from a prospective community-based cohort study of young adults (N=591) followed between ages 19 and 40 years. The sample was stratified to increase the probability of somatic and psychological syndromes. Information was derived from six subsequent semistructured diagnostic interviews conducted by professionals over 20 years. The outcome measures were body mass index (BMI) and obesity (BMI>30). Among women, depressive symptoms before age 17 years were associated with increased weight gain (4.8 vs 2.6% BMI increase per 10 years) representing greater risk for adult obesity (hazard ratio=11.52, P<0.05). Among men, only after controlling for confounders, depressive symptoms before age 17 years were associated with increased weight gain (6.6 vs 5.2% BMI increase per 10 years) in adulthood but not with occurrence of obesity. These associations between childhood depressive symptoms and adult body weight were adjusted for baseline body weight, a family history of weight problems, levels of physical activity, consumption of alcohol and nicotine, and demographic variables. As the magnitude of the associations was high, and depression during childhood is a prevalent and treatable condition, this finding may have important clinical implications for the prevention and treatment of obesity. Whether the results of this study are limited to populations with elevated levels of psychopathology remains to be tested.

What can go wrong when you assume that correlated data are independent: an illustration from the evaluation of a childhood health intervention in Brazil.

The key analytical challenge presented by longitudinal data is that observations from one individual tend to be correlated. Although longitudinal data commonly occur in medicine and public health, the issue of correlation is sometimes ignored or avoided in the analysis. If longitudinal data are modelled using regression techniques that ignore correlation, biased estimates of regression parameter variances can occur. This bias can lead to invalid inferences regarding measures of effect such as odds ratios (OR) or risk ratios (RR). Using the example of a childhood health intervention in Brazil, we illustrate how ignoring correlation leads to incorrect conclusions about the effectiveness of the intervention.

Risk factors for microalbuminuria in black americans with newly diagnosed type 2 diabetes.

We conducted a cross-sectional analysis to describe the prevalence of and risk factors for microalbuminuria among blacks with newly diagnosed type 2 diabetes. Black adults with diagnosed type 2 diabetes mellitus of 2 years' duration or less who presented for care to the Grady Diabetes Clinic (Atlanta, GA) between January 1, 1994, and December 31, 1996, were eligible (n = 1,167). Information obtained at the initial visit included age; sex; body mass index (BMI); serum total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, C-peptide, serum creatinine, and hemoglobin A1c (HbA(1c)) levels; and seated systolic and diastolic blood pressures. Outcome was urine albumin-creatinine (Alb/Cr) ratio at the initial visit. Alb/Cr ratios were categorized as normal (Alb/Cr <25 microgram/mg), microalbuminuric (Alb/Cr, 25 to 250 microgram/mg), and macroalbuminuric (Alb/Cr >250 microgram/mg). Patients with macroalbuminuria or creatinine levels of 2 mg/dL or greater were excluded. We used multiple linear regression to assess the joint association between HbA(1c) level, mean arterial pressure (MAP), and log-transformed Alb/Cr, controlling for other covariates. Of 1,044 patients studied, macroalbuminuria was present in 3.8%, and microalbuminuria, in 23.4%. Alb/Cr was independently associated with increased HbA(1c) level (P = 0.0070), MAP (P = 0.0001), BMI (P = 0.0156), log-transformed triglyceride levels (P = 0.0031), C-peptide level of 6.5 ng/mL or greater (P = 0.0007), serum creatinine level (P: = 0.0068), and male sex (P = 0.0220). The relationship between HbA(1c) level and microalbuminuria was stronger in patients with lower BMIs. Microalbuminuria prevalence was high in this population of urban blacks with newly diagnosed type 2 diabetes. Risk factors associated with increased Alb/Cr included male sex, poor glycemic control, endogenous hyperinsulinemia, high blood pressure, elevated triglyceride levels, and obesity.

Local and remote sustained trigger point therapy for exacerbations of chronic low back pain. A randomized, double-blind, controlled, multicenter trial.

STUDY DESIGN: A randomized, double-blind, controlled, multicenter trial was conducted. OBJECTIVES: To assess the efficacy of neuroreflexotherapy in the management of low back pain. SUMMARY AND BACKGROUND DATA: Neuroreflexotherapy consists of temporary implantation of epidermal devices in trigger points in the back and referred tender points in the ear. METHODS: The rheumatology and rehabilitation departments of three teaching hospitals in Madrid recruited 78 patients with chronic low back pain. These patients were randomly assigned to the control group (37 patients) or to the treatment group (41 patients). Patients in the treatment group underwent one neuroreflexotherapeutic intervention. The control group received sham treatment consisting of placement of the same number of epidermal devices within a 5-cm radius of the target zones. Patients from both groups were allowed to continue drug treatment as previously prescribed. The use of medications during the trial was recorded. RESULTS: Patients underwent clinical evaluations on three occasions: within 5 minutes before intervention, within 5 minutes after intervention, and 45 days later. The preintervention assessment was carried out by the physician from each hospital department who included the patient in the study. Each of the two follow-up assessments were carried out independently by two of three physicians who had no connection with the research team. Patients in the treatment group showed immediate lessening of pain compared with the results in patients in the control group. The pain relief was clinically relevant and statistically significant, and it persisted up to the end of the trial. CONCLUSIONS: Neuroreflexotherapy intervention seems to be a simple and effective treatment for rapid amelioration of pain episodes in patients with chronic low back pain. At this time, the duration of pain relief beyond 45 days has not been evaluated.

Regression models for ordinal responses: a review of methods and applications.

BACKGROUND: Epidemiologists are often interested in estimating the risk of several related diseases as well as adverse outcomes, which have a natural ordering of severity or certainty. While most investigators choose to model several dichotomous outcomes (such as very low birthweight versus normal and moderately low birthweight versus normal), this approach does not fully utilize the available information. Several statistical models for ordinal responses have been proposed, but have been underutilized. In this paper, we describe statistical methods for modelling ordinal response data, and illustrate the fit of these models to a large database from a perinatal health programme. METHODS: Models considered here include (1) the cumulative logit model, (2) continuation-ratio model, (3) constrained and unconstrained partial proportional odds models, (4) adjacent-category logit model, (5) polytomous logistic model, and (6) stereotype logistic model. We illustrate and compare the fit of these models on a perinatal database, to study the impact of midline episiotomy procedure on perineal lacerations during labour and delivery. Finally, we provide a discussion on graphical methods for the assessment of model assumptions and model constraints, and conclude with a discussion on the choice of an ordinal model. The primary focus in this paper is the formulation of ordinal models, interpretation of model parameters, and their implications for epidemiological research. CONCLUSIONS: This paper presents a synthesized review of generalized linear regression models for analysing ordered responses. We recommend that the analyst performs (i) goodness-of-fit tests and an analysis of residuals, (ii) sensitivity analysis by fitting and comparing different models, and (iii) by graphically examining the model assumptions.

Basic models for disease occurrence in epidemiology.

BACKGROUND: One of the epidemiologist's most basic tasks is estimation of disease occurrence. To perform this task, the epidemiologist frequently models variability in disease occurrence using one of three distributions--the binomial, the Poisson or the exponential distribution. Although epidemiologists often use them and their properties appear in standard texts, we know of no text or review that compares and contrasts epidemiological application of these distributions. METHODS: In this commentary, we discuss these three basic distributions. We note key assumptions as well as limitations, and compare results from analyses based on each distribution. RESULTS AND CONCLUSIONS: We illustrate that the three distributions, although superficially different, often lead to similar results. We argue that epidemiologists should often obtain similar results regardless of which distribution they use. We also point out that application of all three distributions can be inappropriate if assumptions of independence or homogeneity of risks fail to hold. Finally, we briefly review how these basic distributions can be used to justify use of other distributions, such as the Gaussian distribution, for studying disease-exposure associations.

A longitudinal analysis of predictors of quitting smoking among participants in a self-help intervention trial.

Predictors of 7-day abstinence from smoking were identified among participants in a randomized self-help smoking-cessation intervention trial conducted from 1985 to 1988 in Seattle, WA. Subjects were adult smokers belonging to a health maintenance organization who responded to an offer of free quitting assistance. Self-reported smoking status was assessed at 8, 16, and 24 months following enrollment. Predictors of abstinence were identified by longitudinal data analysis using Generalized Estimating Equations (GEEs), a modeling approach which handles repeated-measures data and accommodates time-dependent as well as time-independent covariates. Seventeen items emerged as significant (p < .05) predictors, with odds ratios ranging from 1.3 to 2.1. While much of the previous work in smoking-cessation research has focused on demographic and smoking history variables, results of this study indicate that emphasis should also be placed on psychosocial/motivational factors and quitting activities as important predictors of abstinence. Longitudinal data analysis represents a powerful technique for handling correlated (repeated measures) data, which may prove very useful for future studies of smoking cessation as well as other dynamic processes.

The health effects of swimming at Sydney beaches. The Sydney Beach Users Study Advisory Group.

OBJECTIVES: The purpose of the study was to determine the health risks of swimming at ocean beaches in Sydney, Australia. METHODS: From people attending 12 Sydney beaches in the period from December 5, 1989 to February 26, 1990, we recruited a cohort of 8413 adults who agreed to participate in this study. Of these, 4424 were excluded either because they had been swimming in the previous 5 days or because they reported a current illness. Of the remainder, 2839 successfully completed a follow-up telephone interview conducted within 10 days after recruitment. We recorded reported respiratory, gastrointestinal, eye, and ear symptoms and fever that occurred within the 10 days between initial interview on the beach and the follow-up interview. RESULTS: A total of 683 participants (24.0%) reported experiencing symptoms in the 10 days following initial interview. Of these, 435 (63.7%) reported respiratory symptoms. Swimmers were almost twice as likely as nonswimmers to report symptoms. There was a linear relationship between water pollution and all reported symptoms with the exception of gastrointestinal complaints. CONCLUSIONS: Swimmers at Sydney ocean beaches are more likely to report respiratory, ear, and eye symptoms than beachgoers who do not swim. The incidence of these symptoms increases slightly with increasing levels of pollution.

Methadone dose and heroin use during maintenance treatment.

A retrospective study examined the association between methadone dose and in-treatment heroin use as measured by fixed-interval urine testing in a cohort of 62 patients admitted to an Australian maintenance program. Urinalysis and methadone dose data were collected on subjects for a maximum two years and were analysed using Zeger & Liang's (1986) method for modelling longitudinal data. While allowing for patient descriptors and the time period in which urine samples were collected, the relative odds of using heroin were reduced by 2% for every 1 mg increase in the maintenance dose of methadone. It is estimated that the odds of patients maintained on 40 mg of methadone using heroin were 2.2 times those of patients maintained on 80 mg.

Clinic policy and retention in methadone maintenance.

Advantage was taken of a natural experiment to investigate the relationship of clinic objectives and procedures with retention in methadone maintenance. Assessment, maximum dose, and time in treatment data on 238 patients were summarized using Cox regression. While allowing for patient descriptors and maximum dose of methadone, those subjects assigned to a strongly abstinence-oriented program were 26% (95% C.I., 18 to 33%), 98% (66 to 137%), 213% (132 to 322%), and 393% (224 to 651%) more likely to leave treatment in the first, second, third, fourth 6 months of treatment, respectively, than those subjects assigned to a more laissez-faire program.

Interpreting the literature in obstetrics and gynecology: I. Key concepts in epidemiology and biostatistics.

The proper interpretation of research findings in obstetrics and gynecology increasingly requires some understanding of epidemiology and biostatistics. The disciplines of epidemiology and biostatistics are inextricably related; the goal of epidemiology is accurate measurement of the relationship between an exposure and a disease, and statistical methods are required for achieving that objective. Most epidemiologic studies in the obstetrics and gynecology literature can be classified as 1) cross-sectional, 2) case-control, or 3) cohort (follow-up) studies. The 2 x 2 table represents the basic analytic format for all three types of epidemiologic studies. Information from this table can be used to estimate both the magnitude of the exposure-disease relationship and the relative likelihood that chance explains study findings. Accurate measurement of the relationship between an exposure and a disease can be impeded by two major sources of error: bias and chance. In broad terms, biases can be classified as those related to 1) selection, 2) information, and 3) the presence of extraneous variables. Because biases in epidemiologic studies distort measurements, they must be identified, characterized, and, if possible, avoided. When biases cannot be avoided, knowledge of their likely impact on study findings must be assessed. The role of chance is evaluated by statistical testing of the null hypothesis, ie, the hypothesis that two factors are not associated.(ABSTRACT TRUNCATED AT 250 WORDS)

Interpreting the literature in obstetrics and gynecology: II. Logistic regression and related issues.

The goal of epidemiology is accurate measure of the relationship between an exposure and a disease of interest. The control of covariates of the exposure-disease relationship is required to obtain a valid measure. Two types of covariates, confounders and effect modifiers, must be considered. Investigators can design studies to measure and control for the impact of both types of covariates. Design strategies for dealing with covariates include randomization, restriction, and matching. If the impact of a covariate is not eliminated by study design, it must be controlled for during study analysis by use of either stratification or mathematical modeling. Stratified analysis permits an assessment of the exposure-disease relationship for each category of relevant covariates. Although stratification is the best initial approach for controlling covariates, it is often impractical, particularly if more than one or two covariates must be controlled. Multivariate mathematical models are required if multiple covariates are to be controlled. Logistic regression is the mathematical modeling procedure most often used to analyze studies in obstetrics and gynecology. Although there are no uniform rules for building a proper model for regression analysis, useful general strategies are available. It must be emphasized that, though the use of mathematical modeling can control for multiple covariates and thereby improve the chance of obtaining an accurate measure of the exposure-disease relationship, it cannot "fix" data that result from a poorly designed or improperly conducted study.

Psychologic distress as a predictor of mortality.

In a 12-year follow-up study of 610 persons (239 black and 371 white) in Evans County, Georgia, psychologic distress as measured by total score on the Health Opinion Survey, a 20-item questionnaire, was a predictor of mortality. The hazard ratio, comparing the 95th percentile score with the median, was 1.93 (97.5% confidence interval (CI) 1.42-2.62), controlling for age, race, and sex; there was no interaction with these variables. A purer measure of distress symptomatology, based on 18 of the questionnaire items, was also predictive of mortality. The hazard ratio was 1.94 (97.5% Cl 1.33-2.82), controlling for age, race, sex, and the item, "Do you have any sickness or illness problems at the present time?"; no interactions with the latter variables were found. This pattern was not affected in any major way by several modifications of the analyses: 1) controlling also for smoking, serum cholesterol, Quetelet index (weight (kg)/height (m)2), diastolic blood pressure, a social network index, and a social class index; 2) excluding persons with a diagnosis (in 1968) of chronic heart disease, angina pectoris, myocardial infarction, stroke, transient cerebral ischemic attach, or diabetes mellitus, or whose deaths were due to neoplastic disease; and 3) restricting the analyses to the last half of the follow-up period to explore the role of incipient or early physical illness in producing the association. With the restricted samples, confidence intervals included 1.00, which may be attributed to both the substantially smaller samples and the slightly reduced strength of the effect. The evidence is consistent with a causal role for psychologic distress, as measured by the Health Opinion Survey, in subsequent mortality rates.

The association between depressive symptoms and mortality among older participants in the Epidemiologic Catchment Area-Piedmont Health Survey.

The association between depression and two-year mortality risk was assessed in 1,606 elderly community participants in the 1982-83 Epidemiologic Catchment Area-Piedmont Health Survey. Two depression measures were formed from the Diagnostic Interview Schedule (DIS) depressive symptom items. Neither measure was associated with mortality in univariate or multiple logistic regression analyses. The adjusted relative risk of mortality comparing the lowest to highest levels of a three-level depression variable was 0.9 (95% confidence interval = 0.5-1.4). Similar results were obtained with other versions of the depression variables, with each depressive symptom category, and within sex, chronic disease, widowhood status, and age groups. These results indicate that depression does not increase mortality in elderly adults, but the short follow-up, sample characteristics, and operationalization of depression may have affected this association.

Ecology of passive smoking by young infants.

This study provides a detailed description of passive smoking by 433 infants (mean age 18 days) enrolled from a representative population of healthy neonates in central North Carolina during 1986 and 1987. Sixty-four percent (276) lived in households with smokers or had contact with nonhousehold smokers. During the week before data collection, two thirds (184) of these 276 infants reportedly had tobacco smoke produced in their presence. Seventy-five percent of smoking mothers smoked near their infants. The amount smoked by the mother near the infant correlated with the amount smoked near the infant by nonmaternal smokers. Cotinine, an indicator of smoke absorption, was found in the urine of 60% (258) of all study infants. The amount smoked in the infant's presence, as well as the amount smoked farther away from the infant, especially by the mother, were the most significant correlates of the urine cotinine concentration. The results of this study suggest that efforts to reduce passive smoking in young infants should emphasize the importance of the mother's smoking behavior, smoke produced anywhere in the home, and household social influences on smoking behavior near the infant.

Hypertension control in a rural southern community: medical care process and dropping out.

As part of the Edgecombe County High Blood Pressure Control Program, we conducted a medical record review within a private group practice to assess the interrelationships between patient characteristics, the process of medical care, and dropping out of care by hypertensive patients. Twenty-one percent of 641 randomly selected hypertensive patients did not have a clinic visit in the year before their record review date. Loss to follow-up varied from 31% for black men to 13% for white women. More intense prior contact with the medical care system was associated with remaining under medical care for all groups by race and sex. Black men were much less likely to have intense contact with the medical care system than the other groups. Physician aggressiveness in the use of drug therapy was associated with a nearly 40% reduction in the risk of being lost to follow-up. These findings suggest that patient characteristics and several factors that reflect the process of medical care are associated with dropping out of medical care by hypertensive patients.