Scott Barnhart

EFFECTS OF A COMBINATION OF BETA CAROTENE AND VITAMIN A ON LUNG CANCER AND CARDIOVASCULAR DISEASE

BACKGROUND Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. METHODS We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. RESULTS A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. CONCLUSIONS After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.

The Respiratory Effects of Volatile Organic Compounds

Abstract Volatile organic compounds (VOGs) have been implicated as causative agents in asthma and building-related illness. To determine whether a mixture of VOGs could impair lung function or cause airway inflammation among subjects without bronchial hyper responsiveness, the authors conducted a randomized, crossover-design trial of controlled human exposures to filtered air for four hours, VOCs at 25 mg/m3 for four hours, and VOGs at 50 mg/ m3 for four hours, using a VOG mixture based on sampling of indoor environments. VOG exposures caused dose-related increases in lower respiratory, upper respiratory, and non-respiratory symptoms, with no significant change in lung function (FEV1, FVC, or FEF25–75), nasal lavage cellularity or differential cell counts, induced sputum cellularity or differential cell counts, or biomarkers of airway inflammation, including IL-8, LTB4, or albumin in nasal lavage or induced sputum samples. Atopic individuals had significantly reduced FEE25–75 following exposure to VOCs at 50 mg/m3, suggesting that these individuals may be more sensitive to the health effects of VOCs. The authors conclude that reductions in levels of VOCs to substantially less than 25 mg/m3 are required if a “non-irritating” work environment is desired.

Neuropsychological performance among agricultural pesticide applicators

To assess the potential effects on neuropsychiatric performance of chronic occupational exposure to organophosphate insecticides, we performed a prospective longitudinal study of a cohort of apple orchard pesticide applicators and a comparison cohort of beef slaughter-house workers. The study group consisted of 49 applicators and 40 comparison subjects who completed both an initial evaluation (preseason) prior to the onset of the approximately 6-month pesticide spraying season and a follow-up evaluation (postseason) about 1 month following the end of spraying season. The applicator cohort had a greater number (n = 22, 45%) of individuals who identified primary preference for Spanish-language testing than did the comparison cohort (n = 5, 13%). Stratification by language preference revealed no significant differences in background characteristics between the two cohorts, except for fewer years of education in the Spanish-language preference applicators versus control subgroups (5.0 +/- 3.1 vs 7.8 +/- 3.7 years, respectively). After controlling for language preference, there were no statistically significant differences between the applicators and control cohorts on neuropsychological subtests of the computerized test battery. Preseason baseline performance on individual tests was a significant predictor of postseason test performance. After controlling for baseline performance, the only statistically significant exposure related across-season changes in neuropsychological performance was for one subtest (Symbol Digit Substitution) and was confined to the Spanish language preference subgroups, with worse adjusted postseason performance among applicators versus controls (P = 0.001). This study found no clear evidence of clinically significant decrements in neuropsychological performance following one 6-month season of pesticide exposure in a cohort of applicators who were felt to have generally low, intermittent, and well-controlled organophosphate exposures.

Psychiatric comorbidity and functional status in adult patients with asthma

The goals of this study were to characterize the frequency of psychiatric disorders among patients with asthma, and to compare differences in functional status among asthma patients with and without comorbid depression and anxiety disorders. Fifty patients with confirmed asthma were administered the Diagnostic Interview Schedule for DSM-III-R and completed the Medical Outcomes Study Short Form-36 Health Survey. Patients with asthma had a higher lifetime prevalence of major depression, panic disorder, and agoraphobia, but a lower prevalence of social phobia, compared to lifetime prevalence rates for psychiatric disorders in a national probability sample. Participants with comorbid asthma and major depression had poorer physical and mental health functioning and health perception than did asthma patients without major depression. The results suggest that certain psychiatric disorders are common among patients with asthma and that depression is associated with significantly increased functional morbidity. These findings underscore the need for the appropriate detection and treatment of these comorbid conditions.

Statistical design and monitoring of the carotene and retinol efficacy trial (CARET)

CARET is a chemoprevention trial of beta-carotene and vitamin A with lung cancer as the primary outcome. Participants at high risk for lung cancer are drawn from two populations: asbestos-exposed workers and heavy smokers. The intervention is a daily combination of 30 mg beta-carotene and 25,000 IU vitamin A as retinyl palmitate. Nearly 18,000 participants will be followed for a mean 6 years, yielding over 100,000 person-years of follow-up. We project that this sample size will have 80% power to detect a 23% decrease in the incidence of lung cancer cases. The purpose of this paper is to present the values of the key sample size parameters of CARET; our schemes for monitoring CARET for sample size adequacy, incidence of side effects, and efficacy of the study vitamins; an overview of the data collected; and plans for the primary, secondary, and ancillary analyses to be performed at the end of the trial. These approaches to the design, monitoring, and analysis of CARET are applicable for many other prevention trials.

Why increasing availability of ART is not enough: a rapid, community-based study on how HIV-related stigma impacts engagement to care in rural South Africa.

BackgroundStigma is a known barrier to HIV testing and care. Because access to antiretroviral therapy reduces overt illness and mortality, some scholars theorized that HIV-related stigma would decrease as treatment availability increased. However, the association between ART accessibility and stigma has not been as straightforward as originally predicted.MethodsWe conducted a “situational analysis”—a rapid, community-based qualitative assessment to inform a combination HIV prevention program in high prevalence communities. In the context of this community-based research, we conducted semi-structured interviews and focus groups with 684 individuals in four low-resource sub-districts in North West Province, South Africa. In addition to using this data to inform programming, we examined the impact of stigma on the uptake of services.ResultsFindings suggested that anticipated stigma remains a barrier to care. Although participants reported less enacted stigma, or hostility toward people living with HIV, they also felt that HIV remains synonymous with promiscuity and infidelity. Participants described community members taking steps to avoid being identified as HIV-positive, including avoiding healthcare facilities entirely, using traditional healers, or paying for private doctors. Such behaviors led to delays in testing and accessing care, and problems adhering to medications, especially for men and youth with no other health condition that could plausibly account for their utilization of medical services.ConclusionsWe conclude that providing access to ART alone will not end HIV-related stigma. Instead, individuals will remain hesitant to seek care as long as they fear that doing so will lead to prejudice and discrimination. It is critical to combat this trend by increasing cultural acceptance of being seropositive, integrating HIV care into general primary care and normalizing men and youths’ accessing health care.

Investigating clandestine drug laboratories: Adverse medical effects in law enforcement personnel

A retrospective cohort study was conducted among an international group of 46 law enforcement chemists and 13 Washington State clandestine drug laboratory investigation team members with more than 2,800 combined investigations. Each participant completed a questionnaire concerning previous drug laboratory investigations and adverse health effects during response activities. Methamphetamine laboratories accounted for 81-97% of all responses. Total illness incident rates varied between 0.75-3.4% of responses. Most exposures were through inhalation, and many occurred in the years prior to use of personal protective equipment. Symptoms were primarily those of headache and respiratory, mucous membrane, and skin irritation. Most illness episodes occurred during the processing phase of laboratory responses, and none occurred during the entry phase. A majority of illness episodes occurred in laboratories with leak/spills, fire/explosion, or uncontrolled reactions. Responding to an active laboratory was associated with a 7 to 15-fold risk of becoming ill as compared with setup, in-transit, or former (equipment removed) laboratory responses. No other laboratories characteristics were consistently associated with a significantly elevated relative risk of adverse health effects.

ISAAC‐based asthma and atopic symptoms among Ha Noi school children

Childhood asthma and atopy prevalence patterns in the developing world are only beginning to be defined. No such information exists for Vietnam. Estimates would assist in anticipating health service needs as well as add to the growing database on global patterns of atopy. To estimate the prevalence of atopic symptoms in school children in Ha Noi, Vietnam, a cross‐sectional survey was conducted of children aged 5‐ to 11‐years‐old in two schools using the parent self‐administered International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. The response rate was 66.4% (969 responses). The overall prevalence of selected symptoms were: ‘ever wheezed’ 24.9%, ‘wheezed in past 12 months’ 14.9%, ‘ever had asthma’ 12.1%, ‘doctor‐diagnosed asthma’ 13.9%, ‘ever experienced allergic rhinitis (AR) symptoms’ 34.9%, ‘AR‐conjunctivitis symptoms in past 12 months’ 10.7%, ‘ever had hay fever’ 7.8%, ‘doctor‐diagnosed hay fever’ 11.2%, ‘ever had eczema’ 3.3% and ‘doctor‐diagnosed eczema’ 3.2%. Kappa statistics demonstrated high within symptom category consistency for ‘ever had asthma/doctor‐diagnosed asthma’ (0.728) and ‘ever had eczema/doctor‐diagnosed eczema’ (0.906). Age and gender adjusted odds ratios (OR) were also consistently significant across wheeze and allergic rhinitis symptom categories [highest OR = 10.10 (95% CI 6.23–16.35) between allergic rhinoconjunctivitis and wheeze in past 12 months]. There is a high prevalence of ISAAC‐based symptoms in school children in Ha Noi, Vietnam, often above global averages. The high level of association between atopic symptoms suggests some degree of reliability and validity. Childhood atopy symptom prevalence in Vietnam is more similar to that in developed countries rather than developing countries.

Tuberculosis in Health Care Settings and the Estimated Benefits of Engineering Controls and Respiratory Protection

Intra-institutional spread of tuberculosis (Tb) has re-emerged as a substantial public and occupational health threat. To characterize the person-hours and lifetime risks of Tb-related morbidity and mortality, we performed a risk assessment for health care workers (HCWs) developing Tb-related morbidity and mortality at varying levels of exposure, engineering controls, and respiratory protection. Under average conditions of exposure, one Tb skin-test conversion is estimated to occur for every 2650 person-hours of work by unprotected workers. With higher exposures, a skin-test conversion for an unprotected worker may occur in as few as 3 person-hours. Use of respiratory protection is estimated to reduce risks by the following proportions: surgical mask, 2.4-fold; disposable dust, fume, mist, or disposable high-efficiency particulate air filtering (HEPA) mask, 17.5-fold; elastomeric HEPA cartridge respirator, 45.5-fold; or powered air-purifying respirator (PAPR), 238-fold. Assuming a lifetime exposure of 250 hours, the risk of a skin-test conversion is estimated to be 9%. We conclude that HCWs are at substantial risk for Tb-related morbidity and mortality, and that administrative controls, engineering controls, and respirators offer substantial benefits in risk reduction.

Comparison of local risk factors for children's atopic symptoms in Hanoi, Vietnam

Background:  A 1999 study in Hanoi, Vietnam using the International Study on Asthma and Allergies in Childhood (ISAAC) questionnaire showed a high prevalence of atopic symptoms. Identifying risk factors for symptoms in these children may help in understanding the causes for these high estimates.