Longitudinal analysis of leisure noise exposure among adolescents with special focus on portable listening devices: the OHRKAN cohort study.

The aim was to investigate leisure noise exposure and sociodemographic determinants of risky leisure noise exposure over five years in 2148 students visiting grade 9 of any school type in a German city from 2009-2011. Within the OHRKAN cohort study, leisure noise exposure was calculated from literature-retrieved sound pressure levels (SPLs) and self-reported duration of 18 leisure activities at baseline and two follow-ups. Risky exposure was defined as exceeding 85 dB(A) averaged over a 40-h-week. Determinants of risky total leisure noise (TLN) exposure and risky exposure to portable listening devices (PLDs) were investigated using generalised estimating equations (GEEs). Up to 73% of students exceeded noise levels of 85 dB(A) at some timepoint. The noise exposure and importance of different leisure activities changed with increasing age. Risky exposure to TLN and PLDs was associated with lower education, single parent households and being male. Risky PLD exposure was additionally associated with a migrant background. Current prevention measures for leisure noise exposure must be extended to at-risk groups. Besides enhancing campaigns in lower education schools, acoustical insulation in sports halls, noise warnings on tools or in videogames could address especially men. Migrants need education about healthy PLD use in their native language if necessary.

[Exposure of Adolescents to Leisure-Time Noise: Results of the First Follow-Up of the Ohrkan Cohort Study]. / Belastung mit Freizeitlärm unter jungen Erwachsenen: Ergebnisse des ersten Follow-Up der Ohrkan-Kohortenstudie.

OBJECTIVE: Analysis of changes in leisure noise exposure among adolescents during 2.5 years of follow-up. METHODS: The analysis is based on the Ohrkan cohort study. A total of 2 149 9th graders in the City of Regensburg (mostly aged 15-16 years) were recruited between 2009-2011. At 2.5-year follow-up, the participants were asked again about leisure noise exposure. Both at baseline (O-I) and in the follow-up (O-II), self-reported frequency of participation in noisy activities was combined with literature-based values of usual sound levels to calculate the total weekly noise exposure. This exposure was compared to the lower exposure action value (lEAV) of 80 dB(A) given by the occupational health and safety regulations. Logistic regression was used to determine the factors associated with leisure noise exposure above the lEAV. RESULTS: Exposure data from both time points were available for 1 704 adolescents (54% female). The percentage of participants who were exposed to leisure noise exceeding the lEAV increased from 75 to 92% due to more persons visiting discotheques in O-II. In both surveys, the activity reported by the highest percentage of participants and with the longest exposure duration was listening to pop music via portable listening devices (PLD) although the proportion of users decreased slightly. Not being a pupil affected PLD use at volume levels >80 dB (A) whereas older age was associated with noise exposure in discotheques. CONCLUSIONS: O-II shows that adolescents are engaged in leisure activities under harmful noise levels and that noise exposure sources are changing with age. These issues should be considered in the developing of prevention programs.

[Trends in incidence of lung cancer according to histological subtype among men and women in Germany : Analysis of cancer registry data with the application of multiple imputation techniques]. / Trends der Lungenkrebsinzidenz nach histologischem Subtyp bei Männern und Frauen in Deutschland : Analyse von Krebsregisterdaten unter Einsatz von multipler Imputation.

BACKGROUND: Lung cancer can be described by histological subtype, of which small cell, squamous cell and adenocarcinoma are the most common. International data show that adenocarcinoma is becoming the dominant histological subtype of lung cancer although the relative risk due to smoking has been found to be smaller than that for other histological subtypes. OBJECTIVE: The aim of the analysis was to describe the time trends in incidence of lung cancer among women and men in Germany according to histological subtype. MATERIALS AND METHODS: All lung cancer cases (ICD-10 C33-C34) newly diagnosed between 2003 and 2012 and collected by the epidemiologic cancer registries of the German federal states with average completeness of registration of at least 90% were considered and grouped into histologic subtypes. If data on tumor histology were not microscopically verified or unspecific, multiple imputation techniques were applied to estimate the histologic subtype. RESULTS: Among women age-standardized lung cancer rates increased considerably between 2003 and 2012 (annual percent change APC = 2.7%), mostly driven by a rising adenocarcinoma incidence (APC = 4.7%). Among men overall lung cancer rates decreased during the same time (APC = -1.7%). Still, a slight increase in adenocarcinoma incidence was also observed in men (APC = 1.0%). CONCLUSION: The rising incidence of adenocarcinoma of the lung is alarming. The cancer registry data do not allow risk factor analysis. In the international discussion, the introduction of filter cigarettes as well as the changing composition of cigarettes has been hypothesized as being responsible. Further epidemiologic studies are strongly needed.

Usage of personal music players in adolescents and its association with noise-induced hearing loss: A cross-sectional analysis of Ohrkan cohort study data.

OBJECTIVE: To describe personal music player (PMP) usage among adolescents, sociodemographic determinants and association with audiometric notches. DESIGN: Audiometric evaluation to assess hearing status, and standardized questionnaires to evaluate PMP listening behaviors, leisure noise exposures and self-reported hearing loss symptoms. Sociodemographic information was collected using a parent questionnaire. Noise exposure by PMP usage equivalent for a 40 h week was estimated based on self-reported volume and duration of use. STUDY SAMPLE: A total of 2143 students (54% females) attending 9th grade in Regensburg, Germany, during 2009 to 2011. RESULTS: Overall, 85% of the students reported using PMPs. Exposure level exceeded 80 dB(A) in approximately one third, and 85 dB(A) in one quarter, of those who used PMP. An audiometric notch was found in 2.3% of participants, but was not significantly associated with higher PMP exposure. CONCLUSIONS: PMP exposure above the occupational limits of 80 and 85 dB(A) set by the Directive 2003/10/EC may be a risk factor for developing noise-induced hearing loss. Educational measures to ameliorate high risk behaviors in PMP usage are needed, particularly for socially disadvantaged groups.

Audiometric notch and extended high-frequency hearing threshold shift in relation to total leisure noise exposure: An exploratory analysis.

BACKGROUND: Studies investigating leisure noise effect on extended high frequency hearing are insufficient and they have inconsistent results. The aim of this study was to investigate if extended high-frequency hearing threshold shift is related to audiometric notch, and if total leisure noise exposure is associated with extended high-frequency hearing threshold shift. MATERIALS AND METHODS: A questionnaire of the Ohrkan cohort study was used to collect information on demographics and leisure time activities. Conventional and extended high-frequency audiometry was performed. We did logistic regression between extended high-frequency hearing threshold shift and audiometric notch as well as between total leisure noise exposure and extended high-frequency hearing threshold shift. Potential confounders (sex, school type, and firecrackers) were included. RESULTS: Data from 278 participants (aged 18-23 years, 53.2% female) were analyzed. Associations between hearing threshold shift at 10, 11.2, 12.5, and 14 kHz with audiometric notch were observed with a higher prevalence of threshold shift at the four frequencies, compared to the notch. However, we found no associations between total leisure noise exposure and hearing threshold shift at any extended high frequency. CONCLUSION: This exploratory analysis suggests that while extended high-frequency hearing threshold shifts are not related to total leisure noise exposure, they are strongly associated with audiometric notch. This leads us to further explore the hypothesis that extended high-frequency threshold shift might be indicative of the appearance of audiometric notch at a later time point, which can be investigated in the future follow-ups of the Ohrkan cohort.

Early indication of noise-induced hearing loss from PMP use in adolescents: A cross-sectional analysis.

CONTEXT: Distortion product otoacoustic emissions (DPOAEs) may indicate preclinical noise-induced hearing loss (NIHL) in adolescents from unsafe personal music player (PMP) use. AIMS: The objective, therefore, was to observe preclinical signs of NIHL in 9th grade adolescents with clinically normal hearing by comparing DPOAE signals between different levels of A-weighted equivalent PMP exposure. SETTINGS AND DESIGN: Subjects were recruited from all secondary-level schools located in the city of Regensburg, Germany during two academic years 2009/2010 and 2010/2011. SUBJECTS AND METHODS: A-weighted equivalent sound pressure levels (SPLs) for a 40-hour work week (LAeq,40h) were estimated from questionnaire responses on output and duration of PMP use of the previous week. Subjects were then categorized into four levels of exposure: <80, 80-85, >85 to <90, and ≥90 A-weighted Decibel [dB(A)]. DPOAE signals were collected by trained audiological staff, applying a standard optimized protocol, at the Department of Otorhinolaryngology of the University Hospital Regensburg. STATISTICAL ANALYSIS USED: Mean DPOAE signals were compared between levels by unpaired t test. Novel linear regression models adjusting for other leisure noise exposures and with outcome variables DPoutcome and 4 kilo Hertz (kHz) DPOAEs estimated effects between levels. RESULTS: A total of 1468 subjects (56% female, mostly aged 15 or 16 years) were available for analysis. Comparison of DPOAE means by PMP exposure typically showed no greater than 1 dB difference between groups. In fact, comparisons between ≥90 dB(A) and <80 dB(A) presented the least differences in magnitude. Both DPoutcome and 4 kHz linear regression models presented a weak association with the 4-level PMP exposure variable. An expected dose-response to PMP exposure was not observed in any analyses. CONCLUSIONS: DPOAE signal strength alone cannot indicate preclinical NIHL in adolescents.

Total leisure noise exposure and its association with hearing loss among adolescents.

OBJECTIVE: To investigate total leisure noise exposure among adolescents and to assess its association with hearing. DESIGN: Based on self-reported time spent on 19 leisure activities and associated mean sound pressure levels reported in the literature, total leisure noise exposure was evaluated and compared to noise at work limits (> 85 dB(A) = hazardous) in a cross-sectional survey. Tympanometry and pure-tone audiometry was performed in sound isolated rooms. STUDY SAMPLE: The study sample consists of 2143 pupils attending grade nine in any school in a German city 2009-2011 (mean age: 15.4 years; range: 13-19 years). Audiometric data were available for 1837 (85.8%) pupils (53.9% girls). RESULTS: 41.9% of the 2143 adolescents who had provided self-reported data on leisure activities associated with noise exposure were estimated to be hazardously exposed to leisure time noise. The interaction of gender with total leisure time noise exposure was not significant. No association between leisure time noise exposure and audiometric notches could be detected. CONCLUSION: While hearing loss seems seldom in this age group, a high proportion of adolescents aged 15-16 years are exposed to noise levels during leisure time bearing long-term risks of hearing loss.

The prevalence of audiometric notches in adolescents in Germany: The Ohrkan-study.

Although there is concern about increasing hearing loss in adolescents caused by leisure noise exposure, prevalence data are scarce. In an US study, about 16-17% of adolescents were affected by audiometric notches. To estimate the prevalence of audiometric notches in adolescents in Germany, baseline data of the cohort study Ohrkan, recruitment during the school years 2009/2010 and 2010/2011 were analyzed. All students in grade 9 visiting any school in the city of Regensburg were eligible for participation. Data was collected via standardized questionnaires from students and their parents. In addition, students were asked to visit the University Clinics of Regensburg for ear examination including a tympanogram and the determination of hearing thresholds in air conduction audiometry. The prevalence of audiometric notches was determined in students with normal tympanogram in both ears and complete audiometry data. Audiometric notches were defined according to criteria used to analyse US data. Overall, 2149 students (1158 girls, 991 boys mainly aged 15-16 years) of the 3846 eligible adolescents (56%) participated. Among the 1843 adolescents with complete audiometry and tympanometry data, the prevalence of audiometric notches was 2.4% (95% confidence interval 1.7-3.1%). We could not confirm the high prevalence of audiometric notches as reported in National Health and Nutrition Examination Surveys for adolescents in the US. Differences in prevalence might be at least partly due to methodical differences in audiometry. Even if empirical evidence is presently ambiguous, it is reasonable to educate young people about the potential risks of high leisure noise exposure.

Influence of dietary factors, age and nickel contact dermatitis on nickel excretion.

BACKGROUND: Nickel is a frequently detected cause of allergic contact dermatitis. Ingestion of nickel may lead to flares of nickel contact dermatitis. METHODS: We examined nickel excretion in the urine of 164 female patients with and without nickel contact dermatitis. The associations between age, atopic dermatitis, nickel contact dermatitis and nickel exposure through nutrition (e.g. dietary supplements) and by patch tests were investigated prospectively. Nickel was measured with atomic absorption spectrometry with two different standardized methods. RESULTS: A nickel detection limit of 0.2 µg/l was exceeded by all samples. The 95th percentiles of urine nickel concentration were 3.77 µg/l (age 18-30 years) and 3.98 µg/l (age 31-46 years). Bivariate analyses pointed to significantly increased nickel excretion with increasing age, ingestion of dietary supplements, drinking of stagnant tap water, and consumption of nickel-rich food. In the multivariate analysis, age and dietary supplements remained significant predictors of high nickel excretion. A non-significant increase in the median concentration of nickel was observed after the administration of conventional nickel patch tests. Patients with atopic eczema showed urine nickel concentrations similar to those in non-atopic controls. CONCLUSIONS: The 95th percentile of nickel excretion in our study population markedly exceeded the actual reference value of 3 µg/l. Age and consumption of dietary supplements are the most important predictors. The use of stagnant tap water and consumption of nickel-rich food contribute to the total load. These factors should be explicitly mentioned when allergic patients on a low-nickel diet are counselled. In contrast, existing nickel contact sensitization was not more frequent in subjects with higher nickel excretion. Nickel patch testing may cause transient minor systemic nickel exposure. The findings of this study extend our understanding and management of factors associated with nickel allergy.

The Relevance of Leisure Noise to Hearing Threshold Shifts: A Longitudinal Analysis Among Adolescents.

PURPOSE: The aim of this study was to analyze the association of total leisure noise exposure and hearing threshold shifts over 5 years among adolescents enrolled in the Ohrkan cohort study. METHOD: The Ohrkan cohort of 2,148 students aged 13-19 years was recruited from 2009 to 2011 and followed up 5 years later. Complete baseline and follow-up reports on exposure and outcome were available for 989 participants. Leisure noise exposure was assessed by questionnaires, and clinical audiometric examinations were performed. Two outcomes were defined: occurrence of the Niskar notch pattern and audiometry showing maximum hearing threshold values at 3, 4, and 6 kHz (both ears). Longitudinal analysis using generalized estimating equations was performed. RESULTS: High total leisure noise exposure, defined as an energy equivalent of a 40-hr week of > 85 dBA, was estimated for 32.7% of students at baseline and 63.8% at follow-up. A noise notch was observed in 1.1% of adolescents at baseline and 3.3% at follow-up. At baseline, the maximum measured threshold shift was 55 dB, which increased to 85 dB at the follow-up. Longitudinal analysis did not reveal an association between leisure noise exposure and hearing thresholds. Hearing threshold shifts or noise notches were associated with sex, school type, and time point of measurement. CONCLUSIONS: No relationship was found between leisure noise and hearing thresholds. Male adolescents and those attending secondary general schools, with graduation following completion of ninth or 10th grade, had a greater likelihood of developing hearing threshold shifts. Prevention programs should focus on these risk groups. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.19233462.

Relationship between noise annoyance from road traffic noise and cardiovascular diseases: a meta-analysis.

Road traffic noise is an important source of noise annoyance in the community. We performed a meta-analysis to assess whether there is an association between noise annoyance from road traffic noise and cardiovascular diseases (arterial hypertension and ischemic heart disease) in adult population. The meta-analysis included studies that: a. had noise annoyance as exposure, quantified either as "annoyed versus non-annoyed" or with various scales collected by standardized questionnaires; b. arterial hypertension or ischemic heart disease as outcome; c. had included only adult population (age >18 years); d. the studies had to have as effect size odds ratios or relative risk. From the individual studies those odds ratios were selected for meta-analysis which compared most distant categories. Eight studies that fulfilled criteria published between 1992 and 2006 were included in the meta-analysis: 6 studies had a cross-sectional design, 1 study had a case-control-design and 1 study had a cohort design. Increased annoyance was significantly associated with arterial hypertension (pooled risk estimate = 1.16, 95% confidence interval 1.02-1.29) while the association with ischemic heart disease did not reach statistical significance (pooled risk estimate = 1.07, 95% confidence interval 0.99-1.14). No publication bias was evidenced. The results of this meta-analysis demonstrated the existence of a positive and significant association between noise annoyance from road traffic and the risk of arterial hypertension and a positive yet insignificant association between noise annoyance and the risk of ischemic heart disease.

Situational temptation scores and smoking cessation in general care.

The construct of self-efficacy, which is assessed either in confidence- or temptation-related instruments, presumably predicts transitions between the transtheoretical model stages of change and ultimately smoking cessation outcome. To elucidate its predictive potential for smoking cessation in a general care setting, we examined the association of baseline scores of the situational temptations inventory with month 12 smoking status in 577 heavy smokers participating in a cluster-randomized study of physician training and financial incentives for smoking cessation in Germany. At follow-up, abstinence could be validated in 56 patients. The temptation sub- and total scores were not bivariately associated with altered odds of smoking cessation, in contrast to established predictors like the Fagerstrom test of nicotine dependence and the stages of change. They were associated with the Fagerstrom scores, but not with the stages of change. Controlling for both cessation predictors, in particular the positive/social temptation subscore was associated with quitting. Additional studies are needed to fully understand how situational temptations relate to smoking cessation outcomes and explain variance beyond that of more established predictors of cessation.

Atherogenic dyslipidaemia but not total- and high-molecular weight adiponectin are associated with the prognostic outcome in patients with coronary heart disease.

AIMS: Adiponectin is closely related to atherogenic dyslipidaemia and may be a clinical important mediator of recurrent coronary heart disease (CHD). However, studies with emphasis on secondary disease prevention are rare. We report data from a prospective study investigating the prognostic value of adiponectin, its high-molecular weight (HMW) form, and of markers of lipid metabolism in patients after their first acute CHD event. METHODS AND RESULTS: We measured baseline total- and HMW-adiponectin in 1051 patients aged 30-70 years with incident CHD and a prospective follow-up was conducted [median: 56.6 months (interquartile range: 53.2; 57.5)]. During this period, 95 patients (incidence: 22.3/1000 patient years) experienced a secondary cardiovascular disease (CVD) event. After adjustment by Cox proportional hazard models, neither total- nor HMW-adiponectin was associated with secondary CVD events. In contrast, LDL-cholesterol and markers of atherogenic dyslipidaemia were independently associated with secondary CVD events (relative risk per unit increase: LDL-cholesterol: 1.54; 95%CI 1.18-2.01; P = 0.001, triglycerides: 1.58; 95%CI 1.31-1.90; P < 0.0001 and HDL-cholesterol: 0.34; 95%CI 0.14-0.79; P = 0.01). CONCLUSION: Measurement of total- and HMW-adiponectin may add no significant value to risk stratifications in patients with incident CHD. In contrast, approaching atherogenic dyslipidaemia may represent a promising target in secondary prevention programs for high-risk patients.

High sound pressure levels in Bavarian discotheques remain after introduction of voluntary agreements.

While no legal rules or regulations exist in Germany, voluntary measures were introduced to achieve a reduction of sound pressure levels in discotheques to levels below 100 dB(A). To evaluate the current levels in Bavarian discotheques and to find out whether these voluntary measures ensured compliance with the recommended limits, sound pressure levels were measured in 20 Bavarian discotheques between 11 p.m. and 2 a.m. With respect to the equivalent continuous A-weighted sound pressure level for each 30-minute period (L Aeq,30min ), only 4/20 discotheques remained below the limit of 100 dB(A) in all time periods. Ten discotheques had sound pressure levels below 100 dB(A) for the total measurement period (L Aeq,180min ). None of the evaluated factors (weekday, size, estimated age of attendees, the use of voluntary measures such as participation of disc jockeys in a tutorial, or the availability of a sound level meter for the DJs) was significantly associated with the maximal L Aeq, 30min . Thus, the introduction of voluntary measures was not sufficient to ensure compliance with the recommended limits of sound pressure levels.

Lipoprotein-associated phospholipase A2 predicts future cardiovascular events in patients with coronary heart disease independently of traditional risk factors, markers of inflammation, renal function, and hemodynamic stress.

OBJECTIVE: We sought to evaluate whether lipoprotein-associated phospholipase A2 (Lp-PLA2), an emerging marker of cardiovascular risk, is associated with prognosis in patients with coronary heart disease (CHD). METHODS AND RESULTS: Plasma concentrations and activity of Lp-PLA2 were determined in 1051 patients aged 30 to 70 years with CHD who were followed for &4 years. A Cox proportional hazards model was used to determine the prognostic value of Lp-PLA2 after adjustment for various covariates, including markers of inflammation, renal function, and hemodynamic stress. In multivariable analyses, Lp-PLA2 mass and activity were strongly associated with cardiovascular events after controlling for traditional risk factors, severity of CHD, statin treatment, cystatin C, and N-terminal proBNP. The hazard ratio (HR) for recurrent events was 2.65 (95% confidence interval [CI], 1.47 to 4.76) for the top tertile of Lp-PLA2 mass compared with the bottom tertile and 2.40 (95% CI, 1.35 to 4.29) for Lp-PLA2 activity. After additional adjustment for low-density lipoprotein (LDL), the HRs were only moderately attenuated (mass: 2.09; 95% CI, 1.10 to 3.96; activity: 1.81; 95% CI, 0.94 to 3.49, respectively), but the latter was no longer statistically significant. CONCLUSIONS: Increased concentrations of Lp-PLA2 predict future cardiovascular events in patients with manifest CHD independent of a variety of potential risk factors including markers of inflammation, renal function, and hemodynamic stress.

Effects of practitioner education, practitioner payment and reimbursement of patients' drug costs on smoking cessation in primary care: a cluster randomised trial.

OBJECTIVE: To evaluate new strategies to enhance the promotion of smoking cessation in general practice. DESIGN: Cluster randomised trial, 2x2 factorial design. SETTING: 82 medical practices in Germany, including 94 general practitioners. PARTICIPANTS: 577 patients who smoked at least 10 cigarettes per day (irrespective of their intention to stop smoking) and were aged 36-75 years. INTERVENTIONS: Provision of a 2-h physician group training in smoking cessation methods and direct physician payments for every participant not smoking 12 months after recruitment (TI, training+incentive); provision of the same training and direct participant reimbursements for pharmacy costs associated with nicotine replacement therapy or bupropion treatment (TM, training+medication). MAIN OUTCOME MEASURE: Self-reported smoking abstinence obtained at 12 months follow-up and validated by serum cotinine. RESULTS: In intention-to-treat analysis, smoking abstinence at 12 months follow-up was 3% (2/74), 3% (5/144), 12% (17/140) and 15% (32/219) in the usual care, and interventions TI, TM and TI+TM, respectively. Applying a mixed logistic regression model, no effect was identified for intervention TI (odds ratio (OR) 1.26, 95% confidence interval (CI) 0.65 to 2.43), but intervention TM strongly increased the odds of cessation (OR 4.77, 95% CI 2.03 to 11.22). CONCLUSION: Providing cost-free effective drugs to patients along with improved training opportunities for general practitioners could be an effective measure to achieve successful promotion of smoking cessation in general practice.

The diagnosis of a smoking-related disease is a prominent trigger for smoking cessation in a retrospective cohort study.

OBJECTIVE: We evaluated the impact of demographic factors, smoking patterns, and the occurrence of smoking-related diseases on smoking cessation, with a particular emphasis on the temporal relationship between diagnosis of smoking-related diseases and cessation. STUDY DESIGN AND SETTING: A cohort was assembled of participants of a general health screening examination aged 50-74 years. Lifetime smoking habits and medical history were obtained by a self-administered questionnaire. In a retrospective cohort study approach, predictors of cessation among ever-smokers (n = 4,575) were identified using the extended proportional hazards model. RESULTS: Male gender, late onset of smoking, and higher educational level were predictive of cessation. However, the by far strongest predictors of cessation were diagnoses of smoking-related diseases: relative cessation rates in the year of disease occurrence were 11.2 for myocardial infarction (95% confidence interval CI = 8.9-14.0), 7.2 for stroke (95% CI = 5.1-11.6), 2.5 for diabetes mellitus (95% CI = 1.6-4.0) and 4.8 for cancer (95% CI = 3.1-7.4) relative to years before diagnosis of the respective diseases. CONCLUSION: Our results underline the key role of perceived detrimental effects of smoking for cessation. When smokers personally experience the health consequences of smoking, many permanently quit.

Role of cytomegalovirus sero-status in the development of secondary cardiovascular events in patients with coronary heart disease under special consideration of diabetes.

OBJECTIVE: We investigated prospectively the role of cytomegalovirus (CMV) sero-status in the development of secondary cardiovascular disease (CVD) events in patients with coronary heart disease (CHD) under special consideration of diabetes mellitus. BACKGROUND: There have been suggestions of an association between cytomegalovirus infection sero-status and development of secondary cardiovascular events. Patients with diabetes might be at higher risk since they are relatively immunocompromised. METHODS: Patients aged 30-70 undergoing an in-patient rehabilitation program after acute manifestation of coronary heart disease between January 1999 and May 2000 were included in this analysis. CMV status at baseline was measured by serum immunoglobulin G antibodies. Secondary CVD events (myocardial infarction, stroke, and cardiovascular death) were recorded during a mean follow-up period of 33.5 months. RESULTS: Among the 1033 subjects with measured IgG antibody for CMV, 56.5% were sero-positive to CMV at baseline. During follow-up, secondary CVD events occurred among 71 (6.9%) participants. Occurrence of a secondary CVD event was more common among sero-positive than among sero-negative patients (adjusted hazard ratio, HR, 1.31, 95% confidence interval (CI) 0.80-2.20), among patients with diabetes HR 2.00 (95% CI 1.20-3.25). The risk of secondary CVD events was strongly increased among patients with both a positive CMV sero-status and diabetes (adjusted HR 2.58, 95% CI 1.32-5.10) compared to CMV negative, non-diabetic patients, whereas either conditions alone was associated with a weak and non-significant increase in risk only. CONCLUSION: Our results are consistent with a possible moderate increase in risk of secondary CVD events among patients with a positive CMV sero-status, and they indicate a strongly increased risk among CMV positive patients with diabetes.

Chlamydia pneumoniae, heat shock proteins 60 and risk of secondary cardiovascular events in patients with coronary heart disease under special consideration of diabetes: a prospective study.

BACKGROUND: There have been suggestions of an association between Chlamydia pneumoniae, chlamydial heat shock protein (Ch-hsp) 60 and human heat shock protein (h-hsp) 60 infection sero-status and development of secondary cardiovascular events. Patients with diabetes might be at higher risk since they are prone to infections. The objective of this study was to investigate prospectively the role of Chlamydia pneumoniae (CP), chlamydial heat shock protein (Ch-hsp) 60 and a possible intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary cardiovascular disease (CVD) events in patients with coronary heart disease (CHD) under special consideration of diabetes mellitus. METHODS: Patients aged 30-70 undergoing an in-patient rehabilitation program after acute manifestation of coronary heart disease (International Classification of Disease, 9th Rev. pos. 410-414) between January 1999 and May 2000 in one of two participating rehabilitation clinics in Germany were included in this analysis. Chlamydia pneumoniae (CP), chlamydial heat shock protein (Ch-hsp) 60 and human heat shock protein (h-hsp) 60 status at baseline were measured by serum immunoglobulin G and A antibodies. Secondary CVD events (myocardial infarction, stroke, and cardiovascular death) were recorded during a mean follow-up period of 33.5 months (response = 87%). RESULTS: Among the 1052 subjects 37.4% and 39.3% were sero-positive to CP IgA and IgG respectively, 22.2% were sero-positive to Ch-hsp 60 IgG and 8.4% were positive to h-hsp 60 IgG at baseline. During follow-up, secondary CVD events occurred among 71 (6.8%) participants. Occurrence of a secondary CVD event was more common among CP (IgA) and CP (IgG) sero-positive than among sero-negative patients (p-values 0.04 and 0.1, respectively). The risk of secondary CVD events was increased among patients with both a positive CP sero-status and diabetes compared to infection negative, non-diabetic patients and in general, sero-positivity added a hazard to diabetes. The interaction term between infection sero-status and diabetes was not statistically significant. We were not able to show an intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary CVD events in patients with CHD. CONCLUSION: Results from this cohort of 1052 patients with pre-existing CHD cannot exclude a possible moderate increase in risk of secondary CVD events among patients with a positive infection sero-status. However, our study showed no intermediate role of human heat shock protein (h-hsp) 60 sero-status in the development of secondary CVD events in patients with CHD. Larger studies or meta-analysis of multiple studies are needed to address the interaction between infection sero-status and diabetes with adequate power.

Radiation-induced DNA damage and repair in lymphocytes from breast cancer patients and their correlation with acute skin reactions to radiotherapy.

PURPOSE: Repair of radiation-induced DNA damage plays a critical role for both the susceptibility of patients to side effects after radiotherapy and their subsequent cancer risk. The study objective was to evaluate whether DNA repair data determined in vitro are correlated with the occurrence of acute side effects during radiotherapy. METHODS AND MATERIALS: Breast cancer patients receiving radiation therapy after a breast-conserving surgery were recruited in a prospective epidemiologic study. As an indicator for clinical radiosensitivity, adverse reactions of the skin were recorded. Cryo-preserved lymphocytes from 113 study participants were gamma-irradiated with 5 Gy in vitro and analyzed using the alkaline comet assay. Reproducibility of the assay was determined by repeated analysis (n = 26) of cells from a healthy donor. A coefficient of variation of 0.3 was calculated. RESULTS: The various parameters determined to characterize the individual DNA repair capacity showed large differences between patients. Eleven patients were identified with considerably enhanced DNA damage induction, and 7 patients exhibited severely reduced DNA repair capacity after 15 and 30 min. Six patients were considered as clinically radiosensitive, indicated by moist desquamation of the skin after a total radiation dose of about 50 Gy. CONCLUSIONS: Using the alkaline comet assay as described here, breast cancer patients were identified showing abnormal cellular radiation effects, but this repair deficiency corresponded only at a very limited extent to the acute radiation sensitivity of the skin. Because impaired DNA repair could be involved in the development of late irradiation effects, individuals exhibiting severely reduced DNA repair capacity should be followed for the development of late clinical symptoms.