Imaging-based prostate cancer screening among BRCA mutation carriers-results from the first round of screening.

BACKGROUND: Male-carriers of BRCA1/2 gene mutations have an increased risk of prostate cancer (PCa) with a more aggressive phenotype. Current screening-guidelines suggest the use of prostate-specific antigen (PSA) only among BRCA2 carriers. Female carriers have extensive guidelines that include imaging. Our objective was to test the prevalence of PCa among BRCA carriers and examine screening strategies, using PSA and multiparametric magnetic resonance imaging (mpMRI). PATIENTS AND METHODS: We recruited men aged 40-70 years with BRCA1/2 germline mutations and no prior history of prostate biopsy. All men underwent an initial round of screening which included PSA, and prostate mpMRI. PSA was considered elevated using an age-stratified threshold of ≥1 ng/ml for 40-50 years of age, ≥2 ng/ml for 50-60 years of age, and 2.5 ng/ml for 60-70 years of age. Men with elevated PSA and/or suspicious lesion on mpMRI were offered a prostate biopsy. PSA levels, MRI findings, PCa incidence, and tumor characteristics were evaluated. Decision curve analysis was used to compare screening strategies. RESULTS: We recruited 188 men (108 BRCA1, 80 BRCA2), mean age 54 years (9.8). One hundred and ten (57%) had either elevated age-stratified PSA (75; 40%), a suspicious MRI lesion (67; 36%), or both (32; 17%). Of these, 92 (85%) agreed to perform a prostate biopsy. Sixteen (8.5%) were diagnosed with PCa; 44% of the tumors were classified as intermediate- or high-risk disease. mpMRI-based screening missed only one of the cancers (6%), while age-stratified PSA would have missed five (31%). Decision curve analysis showed that mpMRI screening, regardless of PSA, had the highest net benefit for PCa diagnosis, especially among men younger than 55 years of age. We found no difference in the risk of PCa between BRCA1 and BRCA2 (8.3% versus 8.7%, P = 0.91). Ninety percent had a Jewish founder mutation, thus the results cannot be generalized to all ethnic groups. CONCLUSIONS: PCa is prevalent among BRCA carriers. Age may affect screening strategy for PCa in this population. Young carriers could benefit from initial MRI screening. BRCA carriers aged older than 55 years should use PSA and be referred to mpMRI if elevated. TRIAL REGISTRATION: ClinicalTrial.gov ID: NCT02053805.

Challenges of exposure assessment for health studies in the aftermath of chemical incidents and disasters.

Exposure assessment during and after acute chemical incidents and disasters is essential for health studies that may follow. During chemical incidents, the focus usually lies on risk assessment and afterward attention shifts toward possible (long-term) health effects. This may lead to insufficient available data on exposure to study the association between exposure and health outcome, and collection of additional exposure data is often required. Literature on health studies conducted after several chemical incidents was reviewed to obtain better insight on the needs of health studies. Four different types of scenarios were distinguished based on when exposure data were collected and the exposure data used for health studies. These four scenarios gave insight on exposure data needed for conclusive health studies and when different methods of exposure data collection should be used. Literature indicated that adequate and rapid exposure assessment during chemical incidents is vital for health studies, because data that are not collected during or directly after an incident may be irretrievably lost. Poor exposure assessment is not always the only problem in health studies. Problems in health studies including poor exposure assessment may be prevented when the general design and needs of health studies are taken into account when designing contingency plans. Together with measures that will help facilitate funding, design, and coordination of health studies, disaster management programs should, among others, prepare for methods that lead to a swift identification of released substances, determination of concentrations and dispersion of released substances, designing basic questionnaire outlines, and rapid evaluation of the usefulness and necessity of employing biological sampling.

Risk factors for physical symptoms after a disaster: a longitudinal study.

BACKGROUND: Although symptoms such as fatigue, headache and pain in bones and muscles are common after disasters, risk factors for these symptoms among disaster survivors have rarely been studied. We examined predisposing, precipitating and perpetuating factors for these physical symptoms among survivors of a man-made disaster. In addition, we examined whether risk factors for physical symptoms differ between survivors and controls. METHOD: Survivors completed a questionnaire 3 weeks (n=1567), 18 months and 4 years after the disaster. Symptoms and risk factors were measured using validated questionnaires. A comparison group was included at waves 2 and 3 (n=821). Random coefficient analysis (RCA) was used to study risk factors for symptoms. RESULTS: Female gender [beta (beta)=1.0, 95% confidence interval (CI) 0.6-1.4], immigrant status (beta=1.0, 95% CI 0.6-1.4) and pre-disaster psychological problems (beta=0.8, 95% CI 0.1-1.4) were predisposing factors for symptoms. Although disaster-related factors were predictors, the relationship between symptoms and disaster-related factors was not very strong and the magnitude of this association was reduced when perpetuating factors were added. Intrusions and avoidance, depression, anxiety and sleeping problems were important perpetuating factors for physical symptoms among survivors and mediated the association between traumatic stress and physical symptoms. Risk factors for symptoms were comparable between survivors and controls. CONCLUSIONS: The results indicate that health-care workers should be alert for physical symptoms among female survivors, immigrant survivors and individuals with a high level of psychological problems both before and after a disaster.

A longitudinal comparative study of the physical and mental health problems of affected residents of the firework disaster Enschede, The Netherlands.

OBJECTIVES: After the firework disaster in Enschede, The Netherlands, on 13 May 2000, a longitudinal health study was carried out. Study questions were: (1) did the health status change over this period; and (2) how is the health status 18 months after the disaster compared with controls? STUDY DESIGN: A longitudinal comparative study with two surveys at 3 weeks and 18 months after the disaster. METHODS: A control group for the affected residents was included in the second survey. Respondents filled in a set of validated questionnaires measuring their physical and mental health problems. RESULTS: The prevalence of physical and emotional role limitations, severe sleeping problems, feelings of depression and anxiety, as well as intrusion and avoidance decreased from 3 weeks to 18 months after the disaster for the affected residents. Independent of background characteristics and other life events, residents had 1.5 to three times more health problems than the control group; for example, physical role limitations (odds ratio [OR]=1.5, 95% confidence interval [CI] 1.2-2.0) and anxiety (OR=3.1, 95% CI 2.4-4.2). CONCLUSIONS: Although health problems decreased compared with 3 weeks after the disaster, 18 months after the disaster, the affected residents had more health problems than the people from the control group.

Waist circumference as a measurement of obesity in the Netherlands Antilles; associations with hypertension and diabetes mellitus.

OBJECTIVES: To evaluate waist circumference (WC) as a screening tool for obesity in a Caribbean population. To identify risk groups with a high prevalence of (central) obesity in a Caribbean population, and to evaluate associations between (central) obesity and self-reported hypertension and diabetes mellitus. DESIGN: Cross-sectional. SETTING: Population-based study. SUBJECTS: A random sample of adults (18 y or older) was selected from the Population Registries of three islands of the Netherlands Antilles. Response was over 80%. Complete data were available for 2025 subjects. INTERVENTION: A questionnaire and measurements of weight, height, waist and hip. MAIN OUTCOME MEASUREMENT: Central obesity indicator (WC > or =102 cm men, > or =88 cm women). RESULTS: WC was positively associated with age (65-74 y vs 18-24 y) in men (OR=7.7, 95% CI 3.4-17.4) and women (OR=6.4, 95% CI 3.2-12.7). Women with a low education had a higher prevalence of central obesity than women with a high education (OR=0.5, 95% CI 0.3-0.7). However, men with a high income had a higher prevalence of a central obesity than men with a low income (OR=1.7, 95% CI=1.1-2.6). WC was the strongest independent obesity indicator associated with self-reported hypertension (OR=1.7, 95% CI 1.4-2.0) and diabetes mellitus (OR=1.6, 95% CI 1.3-1.9). CONCLUSIONS: The identified risk groups were women aged 55-74 y, women with a low educational level and men with a high income. WC appears to be the major obesity indicator associated with hypertension and diabetes mellitus. SPONSORSHIP: Island Governments of Saba, St Eustatius and Bonaire, the Federal Government of the Netherlands Antilles, Dutch Directorate for Kingdom relationships.

The Saba health study: methodology and main results

'The Saba Health Study' is the first large scale health interview survey of the island. This book presents the main results of the study. It discusses the population's health status, use of health services, and satisfaction with health care. Known health risks, such as smoking, alcohol consumption, and overweight are evaluated and compared with situations on the sister island of Curacao and in western countries. Attention is focused on the identification of risk groups in need of specific policy interventions and health promotion programs (AU)

Serum carotenoids, alpha-tocopherol, and lung function among Dutch elderly.

Antioxidant vitamins (provitamins) may protect against loss of lung function over time. We studied the association between serum carotenoids (alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, zeaxanthin, and lutein), alpha-tocopherol, and lung function among noninstitutionalized Dutch elderly age 65 to 85 yr (n = 528). Multiple linear regression analysis was performed with FEV(1) or FVC as dependent variables and serum levels of antioxidants in quintiles as independent variables. We adjusted for age, gender, height, and pack-years of smoking. Subjects in the fifth quintile of serum beta-carotene had a 195 ml (95% confidence interval [95% CI]: 40 to 351 ml) higher and those in the fifth quintile of alpha-carotene had a 257 ml (95% CI: 99 to 414 ml) higher FEV(1) compared with subjects in the first quintile of these carotenoids. Significant (p < 0.05) positive trends were observed between alpha-carotene, beta-carotene, lycopene, and FEV(1) and between alpha-carotene, beta-carotene, and FVC. Subjects in the highest quintile of the other carotenoids or alpha-tocopherol did not have significantly higher FEV(1) or FVC compared with subjects in the first quintile of these antioxidants. In conclusion, this study shows that from the six major serum carotenoids and alpha-tocopherol studied, particularly alpha-carotene, beta-carotene, and lycopene were positively associated with lung function in the elderly and may be considered as candidates for further investigations.

A case-control study of plasma antioxidant (pro-)vitamins in relation to respiratory symptoms in non-smokers.

The aim of this study was to investigate the relations between plasma levels of antioxidants, beta-carotene and alpha-tocopherol, and chronic respiratory symptoms in Dutch adults who never smoked or were long-term former smokers. Cases (who reported one or more respiratory symptoms) and controls were selected from a population-based cross-sectional study. Plasma concentrations of antioxidants were determined in 491 cases and 496 controls. ORs for the presence of chronic respiratory symptoms were estimated for quintiles of plasma antioxidant concentration after adjustment for age, gender, and body mass index. The OR of respiratory symptoms in all but the highest quintile of plasma beta-carotene decreased and were slightly below one. We saw no meaningful relation with plasma alpha-tocopherol.

Plasma concentrations of the antioxidants beta-carotene and alpha-tocopherol in relation to lung function.

OBJECTIVE: To study the association between plasma antioxidants (beta-carotene and alpha-tocopherol) and lung function in Dutch adults aged 20-59 y. DESIGN: Cross-sectional. SETTING: Population-based study. SUBJECTS: A random sample (n=367) was drawn from all participants (men and women) aged 20-59 y with reproducible lung function measurements in 1995. INTERVENTION: Completion of general questionnaire and physical examination. MAIN OUTCOME MEASUREMENTS: Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and plasma levels of beta-carotene and alpha-tocopherol. RESULTS: SUBJECTS with a high plasma beta-carotene level (90th percentile, that is 0.57 micromol/L) tended to have a higher FEV1 (73 ml, s.e.m. 60 ml; P=0.22) and a higher FVC (147 ml, s.e.m. 76 ml; P=0.05) than subjects with a low plasma beta-carotene level (10th percentile, that is 0.11 micromol/L) after adjustment for age, height, gender, smoking status, pack-years of smoking and alcohol consumption. There was no difference in lung function between subjects with high and low plasma alpha-tocopherol concentrations. CONCLUSIONS: The results suggest that subjects with a high plasma beta-carotene tended to have a higher FVC than subjects with a low plasma beta-carotene concentration which was borderline statistically significant. The difference for FEV1 between high and low levels of plasma beta-carotene tended to be in the same positive direction as that of FVC but did not reach the pre-set statistical significance level. There is no relation between plasma alpha-tocopherol and lung function. SPONSORSHIP: Ministry of Public Health, Welfare and Sports of the Netherlands and the National Institute of Public Health and the Environment.

Dietary influences on chronic obstructive lung disease and asthma: a review of the epidemiological evidence.

The epidemiological evidence for a relationship between diet and indicators of asthma and chronic obstructive pulmonary disease (COPD) is evaluated. The review focuses on the intake of Na, n-3 fatty acids, and antioxidant vitamins as well as fruit and vegetables. Experimental studies suggest that a high-Na diet has a small adverse effect on airway reactivity in asthma patients. However, observational studies provide no clear evidence that high Na intake has adverse effects on airway reactivity or asthma symptoms in open populations. n-3 Polyunsaturated fatty acids, which are present in fish oils, are metabolized into less broncho-constricting and inflammatory mediators than n-6 polyunsaturated fatty acids. Studies in the general adult population suggest that a high fish intake has a beneficial effect on lung function, but the relationship with respiratory symptoms and clinically-manifest asthma or COPD is less evident. Also, experimental studies in asthma patients have not demonstrated an improvement in asthma severity after supplementations with fish oil. Several studies showed a beneficial association between fruit and vegetable intake and lung function, but the relationship with respiratory symptoms and the clinically-manifest disease was less convincing. A similar pattern was found for vitamin C in relation to indicators of asthma and COPD, but there are still conflicting results with respect to vitamin E and beta-carotene. In conclusion, the epidemiological evidence for a beneficial effect on indicators of asthma and COPD of eating fish, fruit and vegetables is increasing. However, the effectiveness of dietary supplementation in open-population samples is often not demonstrated. Several unresolved questions are raised, which should be addressed in future studies on the relationship between diet and respiratory disease.

Modulation of the acute respiratory effects of winter air pollution by serum and dietary antioxidants: a panel study.

This study investigated whether a high dietary intake or serum concentration of antioxidant (pro-) vitamins could attenuate the acute respiratory effects of air pollution in panels of adults (n = 227) aged 50-70 yrs with chronic respiratory symptoms in two winters starting in 1993/1994. Subjects performed daily peak expiratory flow (PEF) measurements in the morning and evening and reported the occurrence of respiratory symptoms in two regions (urban and nonurban) each winter. Logistic regression analysis was used with the prevalences of large PEF decrements as dependent variables and air pollution levels as independent variables. Analyses were performed separately for subjects below and above the median levels of serum beta-carotene and the intake of dietary vitamin C and beta-carotene. Subjects with low levels of serum beta-carotene more often had large PEF decrements when particles <10 microm in diameter or black smoke levels which were higher compared to subjects with high levels of serum beta-carotene. The same results tended to be observed for dietary vitamin C or beta-carotene, but there were less significant air pollution effects in the low dietary antioxidant group. The results suggest that serum beta-carotene and to a lesser extent dietary vitamin C and beta-carotene may attenuate peak expiratory flow decrements due to air pollution in subjects with chronic respiratory symptoms.

Double-blind intervention trial on modulation of ozone effects on pulmonary function by antioxidant supplements.

The aim of this study was to investigate whether the acute effects of ozone on lung function could be modulated by antioxidant vitamin supplementation in a placebo-controlled study. Lung function was measured in Dutch bicyclists (n = 38) before and after each training session on a number of occasions (n = 380) during the summer of 1996. The vitamin group (n = 20) received 100 mg of vitamin E and 500 mg of vitamin C daily for 15 weeks. The average ozone concentration during exercise was 77 microg/m3 (range, 14-186 microg/m3). After exclusion of subjects with insufficient compliance from the analysis, a difference in ozone exposure of 100 microg/m3 decreased forced expiratory volume in 1 second (FEV1) 95 ml (95% confidence interval (CI) -265 to -53) in the placebo group and 1 ml (95% CI -94 to 132) in the vitamin group; for forced vital capacity, the change was -125 ml (95% CI -384 to -36) in the placebo group and -42 ml (95% CI -130 to 35) in the vitamin group. The differences in ozone effect on lung function between the groups were statistically significant. The results suggest that supplementation with the antioxidant vitamins C and E confers partial protection against the acute effects of ozone on FEV1 and forced vital capacity in cyclists.

Dietary intake of antioxidant (pro)-vitamins, respiratory symptoms and pulmonary function: the MORGEN study.

BACKGROUND: A study was undertaken to investigate the relationships between the intake of the antioxidant (pro)-vitamins C, E and beta-carotene and the presence of respiratory symptoms and lung function. METHODS: Complete data were collected in a cross sectional study in a random sample of the Dutch population on 6555 adults during 1994 and 1995. Antioxidant intake was assessed by a semi-quantitative food frequency questionnaire and respiratory symptoms (cough, phlegm, productive cough, wheeze, shortness of breath) were assessed by a self-administered questionnaire. Prevalence odds ratios for symptoms were calculated using logistic regression analysis. Linear regression analysis was used for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC). The results are presented as a comparison between the 90th and 10th percentiles of antioxidant intake. RESULTS: Vitamin C intake was not associated with most symptoms but was inversely related with cough. Subjects with a high intake of vitamin C had a 53 ml (95% CI 23 to 83) higher FEV1 and 79 ml (95% CI 42 to 116) higher FVC than those with a low vitamin C intake. Vitamin E intake showed no association with most symptoms and lung function, but had a positive association with productive cough. The intake of beta-carotene was not associated with most symptoms but had a positive association with wheeze. However, subjects with a high intake of beta-carotene had a 60 ml (95% CI 31 to 89) higher FEV1 and 75 ml (95% CI 40 to 110) higher FVC than those with a low intake of beta-carotene. CONCLUSIONS: The results of this study suggest that a high intake of vitamin C or beta-carotene is protective for FEV1 and FVC compared with a low intake, but not for respiratory symptoms.

Antioxidant supplementation and respiratory functions among workers exposed to high levels of ozone.

Ozone exposure has been related to adverse respiratory effects, in particular to lung function decrements. Antioxidant vitamins are free-radical scavengers and could have a protective effect against photo-oxidant exposure. To evaluate whether acute effects of ozone on lung functions could be attenuated by antioxidant vitamin supplementation, we conducted a randomized trial using a double-blind crossover design. Street workers (n = 47) of Mexico City were randomly assigned to take daily a supplement (75 mg vitamin E, 650 mg vitamin C, 15 mg beta carotene) or a placebo and were followed from March to August 1996. Pulmonary function tests were done twice a week at the end of the workday. During the follow-up, the mean 1-h maximum ozone level was 123 ppb (SD = 40). During the first phase, ozone levels were inversely associated with FVC (beta = -1.60 ml/ppb), FEV1 (beta = -2.11 ml/ppb), and FEF25-75 (beta = -4.92 ml/ppb) (p < 0.05) in the placebo group but not in the supplement group. The difference between the two groups was significant for FVC, FEV1, and FEF25-75 (p < 0.01). During the second phase, similar results were observed, but the lung function decrements in the placebo group were smaller, suggesting that the supplementation may have had a residual protective effect on the lung. These results need to be confirmed in larger supplementation studies.

Acute effects of ozone on pulmonary function of cyclists receiving antioxidant supplements.

OBJECTIVES: To identify whether acute lung function effects of ozone can be modulated by antioxidant vitamin supplementation. METHODS: Amateur cyclists (n = 26) were studied in the summer of 1994 in The Netherlands. Repeated lung function measurements were performed with a rolling seal spirometer after training sessions or competitive races on four to 14 occasions. The cyclists were assigned to two study groups. The supplementation group (n = 12) received antioxidant supplements (15 mg beta-carotene, 75 mg vitamin E, and 650 mg vitamin C) once a day for three months. The control group did not receive supplementation. For each subject, lung function after exercise was regressed on the previous eight hour mean ozone concentration. The individual regression coefficients were pooled for each study group and weighted with the inverse of the variance. RESULTS: The eight hour mean ozone concentration was 101 micrograms/m3 (30 to 205 micrograms/m3). For the supplementation group, there was no effect of ozone on FVC, FEV1, peak expiratory flow (PEF), and maximal mid-expiratory flow (MMEF). For the control group the mean coefficients were negative, except for MMEF. The difference between the groups was 2.08 (95% confidence interval (95% CI) 1.31 to 2.85) ml/microgram/m3 for FVC, 1.66 (95% CI 0.62 to 2.70) for FEV1, 6.83 (95% CI 3.17 to 10.49) for PEF, and 0.42 (95% CI -1.38 to 2.22) for MMEF. CONCLUSION: The results suggest that antioxidant vitamin supplementation protects against acute effects of ozone on lung function in heavily exercising amateur cyclists.

Cigarette smoking and socio-economic indicators as determinants of body fatness in three Southern Chinese communities of China.

Obesity is one of the major risk factors for cardiovascular disease and non-insulin dependent diabetes mellitus. This study describes cigarette smoking and the socio-demographic differences of body fatness in three sub-ethnic distinctive communities in Guangdong Province, China. In this study, 935 adult Chinese (Chauzhou - 203 men and 111 women; Meixian - 169 men and 140 women; Xinhui - 194 men and 118 women) were randomly sampled from three communities. A standard protocol was used to measure stature, body weight, waist and hip circumferences. Body mass index (BMI) and waist-to-hip circumference ratio (WHR) were calculated as measures of total body fatness and abdominal body fatness, respectively. The questionnaire was self-administered and demographic and lifestyle factors were assessed. WHR was positively related to age in men (p=0.0001) and in women (p=0.0001) while BMI was associated with age only in women (p=0.0001). In women, WHR was significantly related to education levels after adjusting for age and BMI (p=0.0300). In men, BMI differed by educational level, after adjusting for age and WHR (p=0.0329). BMI was significantly associated with occupational status in men, after adjusting for age and WHR (p=0.0004). Gross household income was significantly associated with WHR in men, after adjusting for age and BMI (p=0.0469). Male smokers had a significantly lower mean BMI than the non-smokers, after adjusting for age and WHR (p=0.0037). Marital status was not related to body fatness measurements after adjusting for age and WHR. The differences in body fatness in Chinese living in Southern China can not be totally explained by educational level, occupational status, marital status, gross household income and cigarette smoking, particularly in women. Age was the only consistent predictor of abdominal body fatness in both men and women and also of total body fatness in women.