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Responds to a commentary made to an article about ethical issues associated with a randomized trial of periconceptual vitamins.

A correction to the article "A Rank-Based Sample Size Method for Multiple Outcomes in Clinical Trials," that appeared in the 2008 issue is presented.

Analysis of longitudinal data is often complicated by the presence of informative right censoring. This type of censoring should be accounted for in the analysis so that valid slope estimates are attained. In this study, we developed a new likelihood-based approach wherein the likelihood function is integrated over random effects to obtain a marginal likelihood function. Maximum likelihood estimates for the population slope were acquired by direct maximisation of the marginal likelihood function and empirical Bayes estimates for the individual slopes were generated using Gaussian quadrature. The performance of the model was assessed using the geometric and Poisson distributions to model the number of observations for every individual subject. Our model generated valid estimates for the slopes under both distributions with minimal bias and mean squared errors. Our sensitivity analysis confirmed the robustness of the model to assumptions pertaining to the underlying distribution and demonstrated its insensitivity to normality assumptions. Moreover, superiority of the model in terms of accuracy of slope estimates was consistently shown across the different levels of censoring in comparison to the naïve and bootstrap approaches. This model was illustrated using the cohort of renal transplant patients and estimates of the slopes that are adjusted for informative right censoring were acquired. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) impairments are multidimensional, making it difficult to choose a single primary outcome when evaluating treatments to stop or lessen the long-term decline in PD. We review commonly used multivariate statistical methods for assessing a treatment's global impact, and we highlight the novel Global Statistical Test (GST) methodology. We compare the GST to other multivariate approaches using data from two PD trials. In one trial where the treatment showed consistent improvement on all primary and secondary outcomes, the GST was more powerful than other methods in demonstrating significant improvement. In the trial where treatment induced both improvement and deterioration in key outcomes, the GST failed to demonstrate statistical evidence even though other techniques showed significant improvement. Based on the statistical properties of the GST and its relevance to overall treatment benefit, the GST appears particularly well suited for a disease like PD where disability and impairment reflect dysfunction of diverse brain systems and where both disease and treatment side effects impact quality of life. In future long term trials, use of GST for primary statistical analysis would allow the assessment of clinically relevant outcomes rather than the artificial selection of a single primary outcome. © 2009 Movement Disorder Society [ABSTRACT FROM AUTHOR]

We sought to analyze the self-reported hospitalization, emergency department visits, and outpatient visits of Persian Gulf War (deployed; n = 1896) and Persian Gulf War — era (nondeployed; n = 1799) military personnel 5 years postconflict to determine whether these groups had different rates of health care use. Compared with personnel who had not been deployed, personnel who had been deployed were more likely to have visited an emergency department (25% vs 21%; odds ratio [OR] = 1.24; 95% confidence interval [CI] = 1.06, 1.51]). Among these groups, the National Guard and Reserve personnel were more likely to have been hospitalized than were the regular military personnel (OR = 1.65; 95% CI = 1.21, 2.26). (Am J Public Health. 2007;97:2145-2148. doi: 10.2105/AJPH.2006.104299) [ABSTRACT FROM AUTHOR]

The article explores the effect of a high-fiber diet versus a fiber-supplemented diet on C-reactive protein (CRP) level. The results indicate that fiber intake from a diet naturally rich in fiber of from a supplement can reduce levels of CRP. Further research is needed to elucidate the differential effect seen in lean versus obese individuals.

Background: Persons with persistent mental illness are at risk for failure to receive medical services. In order to deliver appropriate preventive and primary care for this population, it is important to determine which chronic medical conditions are most common.Objective: We examined chronic medical comorbidity in persons with schizophrenia using validated methodologies.Design: Retrospective analysis of longitudinal administrative claims data from Wellmark Blue Cross/Blue Shield of Iowa.Participants: Subjects with schizophrenia or schizoaffective disorder (N=1,074), and controls (N=726,262) who filed at least 1 claim for medical services, 1996 to 2001.Measurements: Case subjects had schizophrenia as the most clinically predominant psychotic disorder, based on psychiatric hospitalization, psychiatrist diagnoses, and outpatient care. Controls had no claims for any psychiatric comorbidity. Using a modified version of the Elixhauser Comorbidity Index, inpatient and outpatient claims were used to determine the prevalence of 46 common medical conditions. Odds ratios (ORs) were adjusted for age, gender, residence, and nonmental health care utilization using logistic regression.Results: Subjects with schizophrenia were significantly more likely to have 1 or more chronic conditions compared with controls. Adjusted OR (95% confidence interval [CI]) were 2.62 (2.09 to 3.28) for hypothyroidism, 1.88 (1.51 to 2.32) for chronic obstructive pulmonary disease, 2.11 (1.36 to 3.28) for diabetes with complications, 7.54 (3.55 to 15.99) for hepatitis C, 4.21 (3.25 to 5.44) for fluid/electrolyte disorders, and 2.77 (2.23 to 3.44) for nicotine abuse/dependence.Conclusions: Schizophrenia is associated with substantial chronic medical burden. Familiarity with conditions affecting persons with schizophrenia may assist programs aimed at providing medical care for the mentally ill. [ABSTRACT FROM AUTHOR]

Abstract: Missing data, e.g. patient attrition, are endemic in sleep disorder clinical trials. Common approaches for dealing with this situation include complete-case analysis (CCA) and last observation carried forward (LOCF). Although these methods are simple to implement, they are deeply flawed in that they may introduce bias and underestimate uncertainty, leading to erroneous conclusions. There are alternative principled approaches, however, that are available in statistical software namely mixed-effects models and multiple imputation. In this paper we introduce terminology used to describe different assumptions about missing data. We emphasize that understanding reasons for missingness is a critical step in the analysis process. We describe and implement both linear mixed-effects models and an inclusive multiple imputation strategy for handling missing data in a randomized trial examining sleep outcomes. These principled strategies are compared with “complete-case analysis” and LOCF. These analyses illustrate that methodologies for accommodating missing data can produce different results in both direction and strength of treatment effects. Our goal is for this paper to serve as a guide to sleep disorder clinical trial researchers on how to utilize principled methods for incomplete data in their trial analyses. [Copyright &y& Elsevier]

Background: The optimal setting and number of blood pressure (BP) measurements that should be used for clinical decision making and quality reporting are uncertain. Objective: To compare strategies for home or clinic BP measurement and their effect on classifying patients as having BP that was in or out of control. Design: Secondary analysis of a randomized, controlled trial of strategies to improve hypertension management. (ClinicalTrials.gov registration number: NCT00237692) Setting: Primary care clinics affiliated with the Durham Veterans Affairs Medical Center. Patients: 444 veterans with hypertension followed for 18 months. Measurements: Blood pressure was measured repeatedly by using 3 methods: standardized research BP measurements at 6-month intervals; clinic BP measurements obtained during outpatient visits; and home BP measurements using a monitor that transmitted measurements electronically. Results: Patients provided 111 181 systolic BP (SBP) measurements (3218 research, 7121 clinic, and 100 842 home measurements) over 18 months. Systolic BP control rates at baseline (mean SBP <140 mm Hg for clinic or research measurement; <135 mm Hg for home measurement) varied substantially, with 28% classified as in control by clinic measurement, 47% by home measurement, and 68% by research measurement. Short-term variability was large and similar across all 3 methods of measurement, with a mean within-patient coefficient of variation of 10% (range, 1% to 24%). Patients could not be classified as having BP that was in or out of control with 80% certainty on the basis of a single clinic SBP measurement from 120 mm Hg to 157 mm Hg. The effect of within-patient variability could be greatly reduced by averaging several measurements, with most benefit accrued at 5 to 6 measurements. Limitation: The sample was mostly men with a long-standing history of hypertension and was selected on the basis of previous poor BP control. Conclusion: Physicians who want to have 80% or more certainty that they are correctly classifying patients' BP control should use the average of several measurements. Hypertension quality metrics based on a single clinic measurement potentially misclassify a large proportion of patients. [ABSTRACT FROM AUTHOR]

The article offers information on a study on the effect of psyllium fiber supplementation on C-reactive protein. This study aims to identify whether daily fiber supplementation would lessen levels of inflammatory markers. It was established that psyllium fiber supplementation did not significantly bring down CRP levels in overweight or obese individuals who were taken as subjects for this study.

We analyzed cardiovascular disease mortality risks associated with obesity using participant-level metaanalysis of data from the Black Pooling Project for Black and White individuals. The adjusted relative risks (ARRs) were stronger among White participants than among Black participants for coronary heart disease AAR = 1.21 (95% confidence interval [CI] =1.07, 1.36) versus 0.87 (95% CI = 0.69, 1.09), respectively, and cardiovascular disease ARR = 1.18 (95% CI = 1.07, 1.29) versus 0.91 (95% CI = 0.77, 1.05), repectively. The results suggest that obesity is an independent risk factor in White people, and additional study of body size and disease progression is necessary in the assessment of racial disparities. (Am J Public Health. 2008;98:63-66. doi:10. 2105/AJPH.2006.093781) [ABSTRACT FROM AUTHOR]

We investigated whether Persian Gulf War veterans (GWVs) were more likely than Persian Gulf War-era veterans deployed elsewhere (GEVs) to have noncredible neuropsychological examinations. A total of 301 GWVs and 99 GEVs underwent neuropsychological testing. The credibility of 173 examinations showing impairment was evaluated based on test performances, clinical background, psychometric measures, and other self-report data. All 11 examinations judged less than fully credible by one neuropsychologist, plus 19 examinations judged impaired but credible, were then evaluated independently by two more neuropsychologists. Noncredibility was judged with excellent reliability (93% agreement). Seven examinations were judged noncredible. Rates of noncredibility did not differ between GWVs (1%) and GEVs (4%). The pattern of associations of noncredible examinations with cognitive, psychological, and clinical variables generally indicated defective neuropsychological scores, with no coherent pattern, and personality disorder. Findings supported the validity of noncredibility judgments and suggested that noncredible examinations are not a significant problem in neuropsychological investigations of GWVs. [ABSTRACT FROM AUTHOR]

Objectives. In previous studies, we have shown that obesity is associated with increased cardiovascular disease (CVD) mortality in white women but not in black women. Earlier research suggests that body mass index (BMI) has a greater effect on CVD mortality in younger white females than older white females, whereas this relationship in black women is not as clear. This study examines the effect of age on the association of BMI to CVD in black and white women. Methods. The Black Pooling Project includes data on 2,843 black women with 50,464 person-years of follow-up, and 12,739 white women with 214,606 person-years of follow-up. A Cox proportional hazards model was used to examine the association between BMI and CVD mortality for specific age/race groups. The younger group was <60 years of age and the older group was <60 years of age. Results. In younger white women, the relative risk (95% confidence interval [Cl]) for CVD mortality was significant in obese women (BMI >30 kg/m²) vs. women of normal weight (BMI 18.5-24.9 kg/m²) (1.59 [CI 1.20, 2.09]). Similarly, in older white women, the relative risk for CVD mortality in obese women vs. women of normal weight was significant (1.21 [CI 1.04, 1.41]). There were no such associations for black women. Overweight (BMI 25-29.9 kg/m²) was not associated with increased risk in black or white women. Conclusion. These findings indicate that obesity is associated with a significantly greater risk of CVD mortality among white women, with the strongest association among white women <60 years of age. [ABSTRACT FROM AUTHOR]

Purpose: To examine the patterns of coexisting (comorbid) mental disorders and whether comorbidity influences quality of life ratings in a sample of U.S. veterans.Patients and Methods: The Iowa Gulf War Study Case Validation study evaluated 602 military personnel, two-thirds of whom had symptoms of depression, cognitive dysfunction, or chronic widespread pain, who were activated or on active duty sometime during the first Gulf War (GW). Mental health disorders were defined using the SCID-IV, and the Health Utilities Index Mark 3 (HUI3) was used to measure health-related quality of life (HRQoL). Comorbidity was defined as having two or more mental disorders that spanned across at least two separate categories (e.g., depressive disorders and anxiety disorders).Results: Over 35% of veterans with a current mental disorder had at least one other comorbid mental disorder. Those with mental disorder comorbidity had lower HUI scores than veterans with only one or less mental disorders (mean 0.41 +/- 0.30 vs. 0.72 +/- 0.25, p < 0.0001).Conclusion: The co-occurrence of mental disorders that span at least two mental disorder categories is associated with impaired HRQoL in this veteran population. Early identification of mental health comorbidity may lead to interventions to enhance HRQoL among military personnel. [ABSTRACT FROM AUTHOR]

We assessed resistance rates and trends for important antimicrobial-resistant pathogens (oxacillin-resistant Staphylococcus aureus [ORSA], vancomycin-resistant Enterococcus species [VRE], ceftazidime-resistant Klebsiella species [K-ESBL], and ciprofloxacin-resistant Escherichia coli [QREC]), the frequency of outbreaks of infection with these resistant pathogens, and the measures taken to control resistance in a stratified national sample of 670 hospitals. Four hundred ninety-four (74%) of 670 surveys were returned. Resistance rates were highest for ORSA (36%), followed by VRE (10%), QREC (6%), and K-ESBL (5%). Two-thirds of hospitals reported increasing ORSA rates, whereas only 4% reported decreasing rates, and 24% reported ORSA outbreaks within the previous year. Most hospitals (87%) reported having implemented measures to rapidly detect resistance, but only 50% reported having provided appropriate resources for antimicrobial resistance prevention (53%) or having implemented antimicrobial use guidelines (60%). The most common resistant pathogen in US hospitals is ORSA, which accounts for many recognized outbreaks and is increasing in frequency in most facilities. Current practices to prevent and control antimicrobial resistance are inadequate. [ABSTRACT FROM AUTHOR]

Examines the factors associated with blood pressure and percutaneous injury among health care workers in Iowa. Measurement of the consisted use of barrier precautions; Use of regression analysis; Distribution of types of employment among participants.

: BackgroundThe Agency for Health Care Policy and Research (AHCPR) smoking cessation guideline outlines a set of recommendations for physicians to follow in daily practice. However, the effectiveness of this guideline has not been reported. The goal of this project was to evaluate the effect of the AHCPR smoking cessation guideline on provider practices with smokers and on patient smoking rates.: MethodsPatient survey and chart review data from 138 Veterans Administration (VA) acute care medical centers with outpatient facilities were examined. Data were available from both sources in 1996, 1997, and 1998. At the midpoint of this period (1997), the VA recommended the AHCPR smoking cessation clinical practice guideline for implementation throughout the VA healthcare system.: ResultsFrom 1996 to 1998, both the chart audit and the patient survey showed a significant increase in the percentage of patients in the VA who were counseled about smoking and a significant decrease in the percentage of patients who smoke.: ConclusionsBecause the VA tied the guideline implementation to report cards and other performance-enhancing measures, guideline adherence may have been maximized in this setting. These findings suggest that healthcare systems should take an integrated approach to guideline implementation. [Copyright &y& Elsevier]

This report describes the principal methods used in the development, conduct, and analysis of the research study “Health Assessment of Persian Gulf War Veterans from Iowa” (Iowa Gulf War Study). The methods presented include an outline of the organizational structure, study timeline, hypotheses, outcome definitions, and study design. Adhering to a strict timeline, the study protocol and instruments were developed, and a stratified sample of 3,695 military personnel (76% participation) was located and surveyed by structured telephone interview. The study tracked personnel from all service branches residing nationally and internationally, including those discharged from service. This study required development and implementation of methods appropriate to analysis of data collected in a complex sampling framework and methodological procedures to ensure scientific rigor in a highly public and politicized environment. Statistical analyses were conducted on a priori health outcomes and required development of methods to compute Cochran-Mantel-Haenszel adjusted rate differences. This environment facilitated rapid implementation, critique by scientific and public advisors, a high participation rate, and rapid publication. [Copyright &y& Elsevier]

Abstract Rationale, aims and objectives Although clinical practice guidelines have been promoted widely, there is considerable concern that physicians have not incorporated them into their practice. Models suggest that a ‘knowledge–attitude–behaviour’ sequence is important in modifying physician practice patterns. To address this, we examined physicians’ knowledge of, attitudes towards and compliance with a widely implemented guideline – the Agency for Health Care Policy and Research (AHCPR) smoking cessation guideline. Methods A survey was mailed to a random sample of physicians at 128 veterans health administration facilities, which had implemented the guideline 2 years previously. Results Completed surveys were received from 879 physicians (50.3% response rate). Only 26% of physicians reported receiving a copy or summary of the guideline, 44% reported little or no familiarity with it, 42% did not know if they agreed with it, 40% did not know if they complied with it and 46% did not know if it was effective. However, a high percentage of physicians reported that they always or usually explain the health risks of smoking (86%) and that they always or usually suggest that their smoking patients stop (94%). Conclusions In spite of little familiarity with the guideline, the responding physicians reported practice patterns consistent with adherence to it. Knowledge is only one of a spectrum of barriers that affects physician adherence to guidelines. There are numerous opportunities for health care organizations to overcome the barriers to physician adoption of clinical practice guidelines in their day-to-day practice. [ABSTRACT FROM AUTHOR]

Assesses the prevalence of self-reported symptoms and illnesses among Iowa military personnel deployed during the Gulf War. Comparison of self-reported injuries of Gulf War veterans to those of military personnel who did not serve in the Persian Gulf; Association between Gulf War service and self-reports of injuries requiring medical attention.

Presents a study which investigated the relationship between dietary fiber and inflammatory biomarkers in people with diabetes, hypertension and obesity using a nationally representative 1999-2002 National Health and Nutrition Examination Survey. Research design and methods; Results; Conclusions.

Objective: The statistical analysis for a 2-arm randomised controlled trial (RCT) with a baseline outcome followed by a few assessments at fixed follow-up times typically invokes traditional analytic methods (eg, analysis of covariance (ANCOVA), longitudinal data analysis (LDA)). 'Constrained' longitudinal data analysis (cLDA) is a well-established unconditional technique that constrains means of baseline to be equal between arms. We use an analysis of fasting lipid profiles from the Group Medical Clinics (GMC) longitudinal RCT on patients with diabetes to illustrate applications of ANCOVA, LDA and cLDA to demonstrate theoretical concepts of these methods including the impact of missing data., Methods: For the analysis of the illustrated example, all models were fit using linear mixed models to participants with only complete data and to participants using all available data., Results: With complete data (n=195), 95% CI coverage are equivalent for ANCOVA and cLDA with an estimated 11.2 mg/dL (95% CI -19.2 to -3.3; p=0.006) lower mean low-density lipoprotein (LDL) cholesterol in GMC compared with usual care. With all available data (n=233), applying the cLDA model yielded an LDL improvement of 8.9 mg/dL (95% CI -16.7 to -1.0; p=0.03) for GMC compared with usual care. The less efficient, LDA analysis yielded an LDL improvement of 7.2 mg/dL (95% CI -17.2 to 2.8; p=0.15) for GMC compared with usual care., Conclusions: Under reasonable missing data assumptions, cLDA will yield efficient treatment effect estimates and robust inferential statistics. It may be regarded as the method of choice over ANCOVA and LDA., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background and Purpose: Interventional Management of Stroke (IMS) III is a randomized, parallel arm trial comparing the approach of intravenous tissue-type plasminogen activator followed by endovascular treatment with intravenous tissue-type plasminogen activator alone in patients with acute ischemic stroke presenting <3 hours of symptom onset. The trial intended to enroll 900 subjects to ensure adequate statistical power to detect an absolute 10% difference in the percentage of subjects with good outcome, defined as modified Rankin Scale score of 0 to 2 at 3 months. In April 2012, after 656 subjects were randomized, further enrollment was terminated by the National Institute of Neurological Disorders and Stroke based on the prespecified criterion for futility using conditional power<20%., Methods: Conditional power was defined as the likelihood of finding statistical significance at the end of the study, given the accumulated data to date and with the assumption that a minimum hypothesized difference of 10% truly exists between the 2 groups. The evolution of study data leading to futility determination is described, including the interaction between the unblinded study statisticians and the Data and Safety Monitoring Board in the complex deliberation of analysis results., Results: The futility boundary was crossed at the trial's fourth interim analysis. At this point, based on the conditional power criteria, the Data and Safety Monitoring Board recommended termination of the trial., Conclusions: Even in spite of prespecified interim analysis boundaries, interim looks at data pose challenges in interpretation and decision making, underscoring the importance of objective stopping criteria., Clinical Trial Registration Url: http://www.clinicaltrials.gov. Unique identifier: NCT00359424.

Patients undergoing renal transplantation are prone to graft failure which causes lost of follow-up measures on their blood urea nitrogen and serum creatinine levels. These two outcomes are measured repeatedly over time to assess renal function following transplantation. Loss of follow-up on these bivariate measures results in informative right censoring, a common problem in longitudinal data that should be adjusted for so that valid estimates are obtained. In this study, we propose a bivariate model that jointly models these two longitudinal correlated outcomes and generates population and individual slopes adjusting for informative right censoring using a discrete survival approach. The proposed approach is applied to the clinical dataset of patients who had undergone renal transplantation. A simulation study validates the effectiveness of the approach.

Background and Purpose: Ischemic stroke lesion volumes have proven difficult to analyze due to the extremely skewed shape of their underlying distribution. We introduce an extension of generalized linear models, beta regression, as a possible method of modeling extremely skewed distributions as evidenced in ischemic stroke lesion volumes., Methods: The NINDS rt-PA clinical trials measured ischemic stroke lesion volume as a secondary trial outcome. Three-month lesion volumes from these trials were analyzed using beta regression. A multi-variable regression model associating explanatory variables with ischemic stroke lesion volumes was constructed using accepted model building strategies and compared with the previously published volumetric analysis., Results: Beta regression produced a similar model when compared to the previous analysis published by the study group. All previously identified variables of importance were detected in the model building process. The age by treatment interaction described in previous studies was also found in this analysis, confirming the strong effect age has on stroke outcomes. Further, a treatment effect was elicited in terms of odds ratios, yielding a previously unknown quantification of the effect of rt-PA on lesion volumes., Conclusions: Beta regression proved adept in modeling ischemic stroke lesions and offered the interpretation of covariates in terms of odds ratios. Beta regression is seen as a legitimate alternative to analyze ischemic stroke volumes., (Copyright © 2011 S. Karger AG, Basel.)

Demographic factors such as race, vital status, gender, and age could affect the final renal outcome of patients who undergo renal transplantation. These demographic factors could be assessed at the recipient and donor levels. Repeated measures for blood urea nitrogen (BUN) are typically recorded for each patient following renal transplantation, as a biomarker to assess renal progress. However, once a patient develops renal failure due to graft rejection, no measurement of BUN can be registered and the patient goes back to dialysis. This causes loss of follow-up and incomplete data on BUN measurements, a problem referred to as informative right censoring. If this problem is ignored, inaccurate, and biased estimates will be generated. In this study, unbiased estimates for the rate of change of BUN levels over time adjusted for informative right censoring and demographic factors were acquired using a sophisticated model of analysis. Our results demonstrated that BUN levels for Caucasians were decreasing at a greater rate than African Americans (p < 0.0001). When donors are deceased, African American recipients showed an increase instead of a decrease in their BUN levels following transplantation. Moreover, African Americans showed a decrease in their BUN levels when the donors were African Americans compared with when donors were Caucasians (p = 0.03). Our results also showed that BUN levels were decreasing at a greater rate when donors and recipients were of different gender than when they were of the same gender (p = 0.009). These results suggest that the success of renal transplantation is impacted by the donor/recipient demographic factors.

The notion that eating chocolate would prevent or treat hypertension is appealing to many who produce and enjoy chocolate. Several studies have documented beneficial effects of dark chocolate on insulin action and endothelial function. However, the published studies on chocolate and blood pressure include a relatively small number of subjects, and results are conflicting. In addition, because of secrecy surrounding the production of chocolate and the unique sociocultural context of this popular food, research on efficacy and effectiveness is complex. This commentary summarizes 13 peer-reviewed studies on dark chocolate and blood pressure and raises questions relevant to its future as an evidence-based lifestyle intervention.

Geographic variation in hypertension is hypothesized as contributing to the stroke belt, an area in the southeastern United States with high stroke mortality. No study has examined hypertension by lifetime exposure to the stroke belt. This association was studied in 19,385 participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national population-based cohort. Prevalent hypertension was defined as systolic blood pressure >/=140, diastolic blood pressure >/=90, or use of antihypertensive medications. Stroke belt exposure was assessed by residence at birth, currently, early childhood, adolescence, early adulthood, mid-adulthood, and recently. After adjustment for age, race, sex, physical activity level, body mass index, smoking, alcohol, education, and income, the prevalence of hypertension was significantly more strongly related (P < .0001) with lifetime exposure, adolescence, or early adulthood exposure than exposures at other times. Birthplace and current residence were independently associated with hypertension; however, lifetime, adolescence, or early adulthood exposures were more predictive than joint model with both birthplace and current residence. That adolescence and early adulthood periods are more predictive than residence in the stroke belt for most recent 20-year period suggests community and environmental strategies to prevent hypertension need to start earlier in life., (Copyright 2010 American Society of Hypertension. All rights reserved.)

"Loss to follow-up" can be substantial in substance abuse clinical trials. When extensive losses to follow-up occur, one must cautiously analyze and interpret the findings of a research study. Aims of this project were to introduce the types of missing data mechanisms and describe several methods for analyzing data with loss to follow-up. Furthermore, a simulation study compared Type I error and power of several methods when missing data amount and mechanism varies. Methods compared were the following: Last observation carried forward (LOCF), multiple imputation (MI), modified stratified summary statistics (SSS), and mixed effects models. Results demonstrated nominal Type I error for all methods; power was high for all methods except LOCF. Mixed effect model, modified SSS, and MI are generally recommended for use; however, many methods require that the data are missing at random or missing completely at random (i.e., "ignorable"). If the missing data are presumed to be nonignorable, a sensitivity analysis is recommended.

O'Brien (Biometrics 1984; 40:1079-1087) introduced a rank-sum-type global statistical test to summarize treatment's effect on multiple outcomes and to determine whether a treatment is better than others. This paper presents a sample size computation method for clinical trial design with multiple primary outcomes, and O'Brien's test or its modified test (Biometrics 2005; 61:532-539) is used for the primary analysis. A new measure, the global treatment effect (GTE), is introduced to summarize treatment's efficacy from multiple primary outcomes. Computation of the GTE under various settings is provided. Sample size methods are presented based on prespecified GTE both when pilot data are available and when no pilot data are available. The optimal randomization ratio is given for both cases. We compare our sample size method with the Bonferroni adjustment for multiple tests. Since ranks are used in our derivation, sample size formulas derived here are invariant to any monotone transformation of the data and are robust to outliers and skewed distributions. When all outcomes are binary, we show how sample size is affected by the success probabilities of outcomes. Simulation shows that these sample size formulas provide good control of type I error and statistical power. An application to a Parkinson's disease clinical trial design is demonstrated. Splus codes to compute sample size and the test statistic are provided.

Background: Missing data due to attrition are rampant in substance abuse clinical trials. However, missing data are often ignored in the presentation of substance abuse clinical trials. This paper demonstrates missing data methods which may be used for hypothesis testing., Methods: Methods involving stratifying and weighting individuals based on missing data pattern are shown to produce tests that are robust to missing data mechanisms in terms of Type I error and power. In this article, we describe several methods of combining data that may be used for testing hypotheses of the treatment effect. Furthermore, illustrations of each test's Type I error and power under different missing data percentages and mechanisms are quantified using a Monte-Carlo simulation study., Results: Type I error rates were similar for each method, while powers depended on missing data assumptions. Specifically, power was greatest for the weighted, compared to un-weighted methods, especially for greater missing data percentages., Conclusion: Results of this study as well as extant literature demonstrate the need for standards of design and analysis specific to substance abuse clinical trials. Given the known substantial attrition rates and concern for the missing data mechanism in substance abuse clinical trials, investigators need to incorporate missing data methods a priori. That is, missing data methods should be specified at the outset of the study and not after the data have been collected.

Unlabelled: Our study sought to 1) determine if deployment status is associated with chronic widespread pain (CWP), and 2) evaluate whether veterans with CWP have greater psychiatric comorbidity, higher health care utilization, and poorer health status than veterans without CWP. Five years after the conclusion of the first Gulf War (August 1990 to June 1991), we conducted a cross-sectional study of veterans who listed Iowa as the home of record using a stratified sampling design to determine their health status. We compared the prevalence of CWP between deployed and nondeployed veterans. Logistic and multiple linear regression models were constructed to test whether CWP was associated with comorbidities and health-related outcomes of interest. Five hundred ninety of 3695 veterans interviewed (16%) had CWP. Gulf deployment was associated with higher prevalence of CWP than deployment elsewhere (OR = 2.03, 95%CI = 1.60-2.58), after adjustment. Both deployed and nondeployed veterans with CWP reported more health care utilization and comorbidities and lower health-related quality of life scores than veterans without CWP. Deployed veterans were more likely to have CWP than nondeployed veterans, and CWP was associated with poor health outcomes. Military and medical personnel should be aware that efforts to prevent, identify, and treat CWP in veterans returning from the current war may be needed., Perspective: This article indicates that deployed veterans may have an increased risk for development of CWP, which is associated with greater healthcare utilization and comorbidity and lower quality of life. The risk of poor health outcomes suggests that veterans returning from the present conflict should be screened for CWP on their return.

Background: Teaching cancer prevention and detection is important in health professional education. It is desirable to select a comprehensive framework for teaching oral cancer (OC) prevention and detection skills., Methods: The PRECEDE-PROCEED model was used to design a randomized pretest and posttest study of the OC prevention and detection skills of dental students (n = 104). OC knowledge, opinions, and competencies were evaluated., Results: Second year students in the intervention group were more competent than those in the control group., Conclusions: The novel use of PRECEDE-PROCEED sets a precedent for designing a standardized OC curriculum for a wide range of health professional disciplines.

Background: Nephrogenic systemic fibrosis is a debilitating disease occurring exclusively in patients with renal failure. The aetiology of nephrogenic systemic fibrosis is unclear, but recent reports suggest that exposure to gadolinium for enhancement of magnetic resonance imaging may play a role. In the present study, we assessed the association of exposure to gadolinium with the development of nephrogenic systemic fibrosis in patients with various stages of chronic kidney disease., Methods: We analysed the exposure to gadolinium and development of nephrogenic systemic fibrosis in 849 patients on renal replacement therapy over 5 years. We also performed inquiry of development of the nephrogenic systemic fibrosis in 592 patients exposed to gadolinium and estimated to be in stages 3 and 4 of chronic kidney disease., Results: In 849 patients undergoing chronic dialysis from 2001 through 2006 time period, four of the 261 who had received gadolinium (1.5%) and none of the 588 not exposed to gadolinium developed clinically apparent disease. The odds ratio for developing nephrogenic systemic fibrosis was 6.671 [95% confidence interval (CI) 1.537-53.97] in patients with a single gadolinium exposure compared to patients without gadolinium exposure. This ratio increased to 44.5 (95% CI 2.362-2913) in patients with multiple gadolinium exposures compared to patients not receiving gadolinium. None of the 592 patients estimated to be in stage 3 or 4 of chronic kidney disease developed nephrogenic systemic fibrosis after exposure to gadolinium., Conclusion: Gadolinium exposure is associated with nephrogenic systemic fibrosis in patients on chronic renal replacement therapy at a low rate. This association appears to increase with repeated exposure to gadolinium. Since nephrogenic systemic fibrosis may be clinically occult, its prevalence may be higher than reported. Despite this association, it is unclear if gadolinium is the sole or most important factor in the pathogenesis of the disease.

Although communications competency is recommended by the American Dental Education Association, only a few (n=5) dental schools report evaluating students' skills using a competency examination for communication. This study used an objective structured clinical examination (OSCE) to evaluate dental students' competency in interpersonal and tobacco cessation communication skills. All students were evaluated on their interpersonal communication skills at baseline and at six months post-OSCE by standardized patients and on their tobacco cessation communication skills by two independent raters. First- and second-year dental students (n=104) were randomized to a control or intervention group. One month after the baseline OSCE, students in the intervention group participated in a two-hour training session in which faculty members communicated with a standardized patient during a head and neck examination and counseled the patient about tobacco cessation. There were no statistically significant differences from baseline to post-test between the intervention and control group students as measured by the OSCE. However, among first-year students, both the intervention (n=23) and control (n=21) groups significantly increased in tobacco cessation communication scores. Second-year students in both intervention (n=24) and control (n=28) groups declined in interpersonal communication skills from baseline to post-test. Overall, this one-shot intervention was not successful, and results suggest that a comprehensive communication skills training course may be more beneficial than a single, brief training session for improving dental students' communication skills.

Objective: We sought to determine the predictors of incident chronic widespread pain (CWP), specifically, the effect of preexisting symptoms, stress, and psychosocial factors in the subsequent development of CWP among veterans from the first Gulf War (GW)., Methods: We conducted a structured telephone survey (baseline) of military personnel originally from Iowa who were either eligible for or deployed to Operation Desert Shield/Desert Storm, approximately 5 years postconflict. We conducted a follow-up, clinical, in-person study of those who met a priori-defined outcomes of symptoms of cognitive dysfunction, depression, or CWP, and also a sample of those who did not meet any of the outcomes of interest., Results: A total of 370 of 602 evaluated GW veterans were free of CWP 5 years postconflict. At follow-up, 69 (19%) of these had developed CWP. A positive family history of medically unexplained persistent symptoms [odds ratio (OR)=4.8 (2.3, 13.2)] was strongly associated with CWP. At baseline, individuals who reported preexisting symptoms of bronchitis [OR=4.9 (1.9, 12.3)] and cognitive dysfunction [OR=2.1 (1.1, 4.2)] were more likely to develop CWP. Alcohol use [OR=0.2 (0.1, 0.7)] was protective against CWP. Rather than combat-related exposure per se, the perception of stress at the time of the GW [OR=1.6 (1.1, 2.3)] correlated with CWP., Discussion: Among the GW veterans evaluated longitudinally in this study, family history, predeployment symptoms, and the level of perceived stress during the GW were associated with subsequent development of CWP.

Background: Cardiac surgical procedures can be associated with significant morbidity and mortality. Recently, it has been recognized that statins might induce multiple biologic effects independent of lipid lowering that could potentially ameliorate adverse surgical outcomes. Accordingly, this study tested the central hypothesis that pretreatment with statins before cardiac surgery would reduce adverse postoperative surgical outcomes., Methods: Demographic and outcomes data were collected retrospectively for 3829 patients admitted for planned cardiac surgery between February 1994 and December 2002. Statin pretreatment occurred in 1044 patients who were comparable with non-statin-pretreated (n = 2785) patients with regard to sex, race, and age. Primary outcomes examined included postoperative mortality (30-day) and a composite morbidity variable., Results: The odds of experiencing 30-day mortality and morbidity were significantly less in the statin-pretreated group, with unadjusted odds ratios of 0.43 (95% confidence interval [CI], 0.28-0.66) and 0.72 (95% CI, 0.61-0.86), respectively. Risk-adjusted odds ratios for mortality and morbidity were 0.55 (95% CI, 0.32-0.93) and 0.76 (95% CI, 0.62-0.94), respectively, by using a logistic regression model and 0.51 (95% CI, 0.27-0.94) and 0.71 (95% CI, 0.55-0.92), respectively, in the propensity-matched model, demonstrating significant reductions in 30-day morbidity and mortality. In a subsample of patients undergoing valve-only surgery (n = 716), fewer valve-only patients treated with statins experienced mortality, although these results were not statistically significant (1.96% vs 7.5%)., Conclusions: These findings indicate that statin pretreatment before cardiac surgery confers a protective effect with respect to postoperative outcomes.