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Objectives: Current research suggests that dementia care management (DCM) can decrease burden and associated health impairments of caregivers. The objective of this secondary analysis is to investigate the impact of DCM on multifaceted caregivers’ burden dimensions by differentiating between objective and subjective burden. Methods: A sample of n = 317 dyads of caregivers and community-dwelling people with dementia (PwD) participated in a general practitioner-based, cluster-randomized intervention trial (Identifier:NCT01401582) with two arms and comprehensive data assessment at baseline and 12-month follow-up. Data provided by the caregiver included an inventory with 88 items in 20 different dimensions. Results: Caregivers in the intervention ‘DCM’ group showed decreased caregiver burden, especially in caregivers’ objective burden due to caring (i.e. emotional support), caregivers’ subjective burden due to behavior change (i.e. cognition, aggression and resistance, depression, late symptoms) and caregivers’ subjective burden due to perceived conflicts between needs and responsibilities to care (i.e. financial losses) compared to caregivers in the control ‘care as usual’ group, which showed significant increased caregiver burden after 12 months. Conclusion: Our findings support evidence for the effectiveness of DCM to lower family dementia caregivers' burden in multifaceted dimensions. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal lobar degeneration (FTLD) is the second-most common cause of young-onset dementia. Personality and behavior changes lead to high caregiver stress and burden, but little support is available. Our aim is to present the evidence on the characteristics, challenges and unmet needs of caregivers as well as on possible interventions., Methods: We conducted a scoping review on caregiver burden using PubMed, Web of Science and ScienceDirect. A total of 69 articles were considered eligible and were analyzed in the present study., Results: Through the analysis of 69 empirical articles, our results show that caregivers of patients with FTLD are often younger in age, have children and find behavioral disturbances to be the most burdensome. Nine studies assessed the needs of and support for caregivers. Ten studies compared the burden in different forms of FTLD, 19 compared FTLD to other types of dementia, and one compared the caregiver burden between two countries. Eight studies reported on interventions for caregivers or interventions taking burden into account. One study assessed the support structure for caregivers of FTLD patients. Five case reports, eight research overviews and three reviews addressed specific needs and challenges., Conclusions: Further research should reproduce and validate efficacious interventions and focus on underage children of FTLD patients and findings from non-Western countries. Additionally, support structures for FTLD caregivers should be assessed and extended. Awareness both in the wider population and among healthcare professionals is an urgent need for the future.

Background: Up to two-thirds of dementia care is provided by family caregivers who often experience high burden, little support and adverse health outcomes. Enabling and supporting family caregivers to provide care at home prevents early institutionalisation of the person with dementia and alleviates the economic burden of dementia in the long term. General practitioners (GPs), as the first point of contact, have a key role in identifying and managing burden and care needs of family caregivers. However, in routine care, this opportunity is often limited by time constraints and even if caregiver needs are recognised, detailed information about regionally available support and advice on healthcare services is often lacking., Methods: This is a cluster randomised, controlled trial investigating the clinical use and cost-effectiveness of a digitally supported care management programme for caregivers of people with dementia (PwD). Five hundred family caregivers will be randomised at GP offices, specialist practices and memory clinics, with about n=250 participants per arm. Participants are eligible if they are the primary family caregiver of a PwD, are at least 18 years of age and provide informed consent. Participants in the intervention group will receive an individualised care management plan, which will be carried out by qualified study nurses in collaboration with the treating GP. All participants will receive a baseline assessment and a 6-months follow-up assessment. Participants in the wait-list control group will receive usual care. Starting at the 6 months' follow-up, the former controls will also receive an individualised management plan. Primary outcomes are the number of unmet needs (incl. the Camberwell Assessment of Need for the Elderly, CANE) and health-related quality of life (EQ-5D-5L) at 6 months. Secondary outcomes include caregiver burden (Zarit Burden Interview, ZBI), social support (Lubben Social Network Scale, LSNS), the use of medical and non-medical services (Questionnaire for the Use of Medical and Non-Medical Services, FIMA) and resource utilisation (Resource Utilisation in Dementia, RUD). The primary analysis will be based on intention-to-treat. Between- and within-group analyses and a cost-effectiveness analysis will be conducted to estimate the effect of the tablet PC-based care management programme. This trial is funded by the German Federal Joint Committee (G-BA) Innovation Fund., Discussion: The findings of this trial will be useful in informing and improving current healthcare system structures and processes to support family dementia caregivers within routine care practices., Trial Registration: ClinicalTrials.gov NCT04037501 . Registered on 30 July 2019.

Background: Although there are a number of support services accessible for most family dementia caregivers, many caregivers reject available and affordable support. Previous research suggests that rejections of support services may result from insufficient fit of available services with caregivers' unmet needs and a lack of acknowledgement of caregivers' unmet needs and associated support services. The present study investigates (a) the number, proportion and types of caregivers' rejection on recommended tailored support, (b) socio-demographic and clinical determinants of caregiver's rejection of both people with dementia (PwD) and caregivers, and (c) caregivers' health-related variables related to caregivers' rejection., Methods: Caregivers' rejection of tailored support services was identified based on a standardized, computerized unmet needs assessment conducted by dementia-specific qualified nurses. The present analysis is based on data of n = 226 dyads of caregivers and their community-dwelling PwD who participated in a general practitioner (GP)-based, cluster-randomized intervention trial. The trial was approved by the Ethical Committee of the Chamber of Physicians of Mecklenburg-Western Pomerania, registry number BB 20/11. Data analyses were conducted using Stata/IC 13.1. We conducted Welch's t-test, Pearson's product-moment correlation, and conditional negative binomial regression models with random effects for GP to account for over-dispersed count data., Results: In sum, n = 505 unmet needs were identified and the same number of tailored recommendations were identified for n = 171 family dementia caregivers from the intervention group at baseline. For n = 55 family dementia caregivers not a single unmet need and recommendation were identified. A total of 17.6% (n = 89) of the recommendations were rejected by caregivers. Rejection rates of caregivers differed by type of recommendation. Whereas caregivers' rejection rate on recommendations concerning mental health (3.6%), physical health (2.5%), and social, legal, and financial affairs (0%) were low, caregivers' rejection rates concerning social integration (especially caregiver supporting groups) was high (71.7%). Thus, the rejections of family dementia caregivers are mainly linked to the delegation to caregiver supporting groups. Caregivers' rejections were mainly related to personal factors of caregivers (n = 66), service-related factors (n = 6), relational factors (n = 1), and other factors (n = 17). Furthermore, our results showed that the number of caregivers' rejections was associated with a higher functional status of the PwD and are mainly associated with the rejection of caregiver supporting groups. Thus, caregivers visit supporting groups more often when the PwD shows low abilities in activities of daily living. Importantly, this is independent of the status of cognition and depression of the PwD as well as the physical and mental health of the family dementia caregivers., Conclusions: Our results underline the importance of understanding factors that determine caregivers' rejection of support services. These need to be specifically addressed in tailored solutions for caregivers' support services., Trial Registration: ClinicalTrials.gov Identifier: NCT01401582 (date: July 25, 2011, prospective registered).

In March 2019 the Ethics Conference of the German Center for Neurodegenerative Diseases (DZNE) was held for the fifth time. It was organized by the DZNE Rostock/Greifswald site and chaired by Prof. Wolfgang Hoffmann. The conference provided scientists, physicians, representatives of the German Alzheimer Society, (informal) caregivers of people with dementia (PwD), and other interested people with the opportunity to talk about the opportunities and limitations of research on and for PwD.Nationally and internationally recognized experts on healthcare services research, clinical research, nursing research, (geriatric) psychiatry, interdisciplinary ageing research, economic law, and psychotherapy discussed the pros and cons of a multitude of topics like self-determination, research participant decree, informed consent, and participation of PwD in research. The aim of the event was to reconcile the view of practice pleading for an ethically correct, human treatment of PwD and respecting their autonomy with participation in (clinical) studies. Experts controversially discussed and consolidated different points of view of practice and research.

Background: Drug-related problems (DRP) are common in the elderly population, especially in people living with dementia (PwD). DRP are associated with adverse outcomes that could result in increased costs., Objective: The objective of the study was to analyze the association between DRP and healthcare costs in PwD., Methods: The analysis was based on the cross-sectional data of 424 PwD. Compliance, adverse effects, and drug administration of prescribed and over-the-counter drugs taken were assessed. DRP were identified and classified by pharmacists using an adapted German version of "PIE-Doc®". Healthcare utilization was assessed retrospectively used to calculated costs from a public payer perspective using standardized unit costs. The associations between DRP and healthcare costs were analyzed using multiple linear regression models., Results: 394 PwD (93%) had at least one DRP. An inappropriate drug choice was significantly associated with increased total costs (b = 2,718€; CI95% 1,448-3,988) due to significantly higher costs for hospitalization (b = 1,936€; 670-3,202) and for medications (b = 417€; 68-765). Problems with medication dosage and drug interactions were significantly associated with higher medication costs (b = 679€; 31-1,328; and b = 630€; 259-1,001, respectively)., Conclusions: DRP could significantly lead to adverse outcomes for PwD and healthcare payers, reflected by a higher hospitalization and costs, respectively. Further research is needed to clarify on interventions and approaches efficiently avoiding DRP and on the effect on patient-reported and economic outcomes.

Introduction: The purpose of this study was to determine the cost-effectiveness of collaborative dementia care management (DCM)., Methods: The cost-effectiveness analysis was based on the data of 444 patients of a cluster-randomized, controlled trial, conceptualized to evaluate a collaborative DCM that aimed to optimize treatment and care in dementia. Health-care resource use, costs, quality-adjusted life years (QALYs), and incremental cost per QALY gained were measured over a 24-month time horizon., Results: DCM increased QALYs (+0.05) and decreased costs (-569€) due to a lower hospitalization and a delayed institutionalization (7 months) compared with usual care. The probability of DCM being cost-effective was 88% at willingness-to-pay thresholds of 40,000€ per QALY gained and higher in patients living alone compared to those not living alone (96% vs. 26%)., Discussion: DCM is likely to be a cost-effective strategy in treating dementia and thus beneficial for public health-care payers and patients, especially for those living alone., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The sectorization of health-care systems leads to inefficient treatment, especially for elderly people with cognitive impairment. The transition from hospital care to primary care is insufficiently coordinated, and communication between health-care providers is often lacking. Consequences include a further deterioration of health, higher rates of hospital readmissions, and institutionalization. Models of collaborative care have shown their efficacy in primary care by improving patient-related outcomes. The main goal of this trial is to compare the effectiveness of a collaborative care model with usual care for people with cognitive impairment who have been admitted to a hospital for treatment due to a somatic illness. The aim of the intervention is to improve the continuity of treatment and care across the transition between the in-hospital and adjoining primary care sectors., Methods/design: The trial is a longitudinal multisite randomized controlled trial with two arms (care as usual and intersectoral care management). Inclusion criteria at the time of hospital admission due to a somatic illness are age 70+ years, cognitive impairment (Mini Mental State Examination, MMSE ≤26), living at home, and written informed consent. Each participant will have a baseline assessment at the hospital and two follow-up assessments at home (3 and 12 months after discharge). The estimated sample size is n = 398 people with cognitive inmpairement plus their respective informal caregivers (where available). In the intersectoral care management group, specialized care managers will develop, implement, and monitor individualized treatment and care based on comprehensive assessments of the unmet needs of the patients and their informal caregivers. These assessments will occur at the hospital and in participants' homes. Primary outcomes are (1) activities of daily living, (2) readmission to the hospital, and (3) institutionalization. Secondary outcomes include (a) frailty, (b) delirium, (c) quality of life, (d) cognitive status, (e) behavioral and psychological symptoms of dementia, (f) utilization of services, and (g) informal caregiver burden., Discussion: In the event of proving efficacy, this trial will deliver a proof of concept for implementation into routine care. The cost-effectiveness analyses as well as an independent process evaluation will increase the likelihood of meeting this goal. The trial will enable an in-depth analysis of mediating and moderating effects for different health outcomes at the interface between hospital care and primary care. By highlighting treatment and care, the study will provide insights into unmet needs at the time of hospital admission, and the opportunities and barriers to meeting those needs during the hospital stay and after discharge., Trial Registration: ClinicalTrials.gov, NCT03359408 ; December 2, 2017.

Background: People with dementia (PwD) suffer from coexisting medical conditions, creating complex clinical challenges and increasing the risk of poor outcomes, which could be associated with high healthcare cost., Objective: To describe the prevalence of comorbidity in PwD and to analyze the association between comorbidity in dementia diseases and healthcare costs from a payer's perspective., Methods: This cross-sectional analysis was based on n = 362 PwD of the DelpHi-MV trial (Dementia: Life-and person-centered help in Mecklenburg-Western Pomerania). Comorbidity was assessed using the Charlson comorbidity index (CCI) and was categorized into low, high, and very high comorbidity. Healthcare resource utilization and unit costs were used to calculate costs. Multivariable regression models were applied to analyze the association between comorbidity and costs., Results: Comorbidity was highly prevalent in the sample. 47% of PwD had a very high, 37% a high, and 16% a low comorbidity in addition to dementia. The most prevalent co-existing comorbidity were diabetes mellitus (42%), peripheral vascular disease (28%) and cerebrovascular disease (25%). Total costs significantly increased by 528€ (SE = 214, CI95 = 109-947, p = 0.014) with each further comorbidity, especially due to higher cost for medication and medical aids. Compared with a low comorbidity, a very high comorbidity was significantly associated with 818€ (SE = 168, CI95 = 489-1147, p < 0.001) higher medication costs and 336€ (SE = 161, CI95 = 20-652, p = 0.037) higher cost for medical aids. There were no significant association between a higher comorbidity and cost for formal care services., Conclusions: Comorbidity in PwD represents a substantial financial burden on healthcare payers and is a challenge for patients, healthcare providers, and the health systems. Innovative approaches are needed to achieve a patient-oriented management of treatment and care in comorbid PwD to reduce long-term costs.

Background: Caregivers providing informal care for people with dementia (PwD) often report unmet needs, burden, and health impairments. Optimal support for family dementia caregivers will likely benefit from better understanding and assessment of the prevalence and types of caregivers' unmet needs and associated socio-demographic and clinical characteristics., Objective: The present study investigates 1) the number and types of caregivers' unmet needs, 2) socio-demographic and clinical characteristics of both PwD and caregivers, and 3) caregivers' burden and health-related outcomes that are related to caregivers' unmet needs., Methods: The present analyses are based on cross-sectional data of n = 226 dyads of caregivers and their community-dwelling PwD participating in a comprehensive standardized, computer-based caregivers' needs assessment within a general practitioner (GP)-based, cluster-randomized intervention trial., Results: A total of n = 505 unmet needs were identified for n = 171 caregivers from the intervention group at baseline. Only 24.3% caregivers reported no unmet need (n = 55), whereas 75.7% caregivers had at least one unmet need (n = 171). Caregivers had on average 2.19 unmet needs (mean = 2.19, SD = 2.15). Specifically, 53.1% of caregivers had one up to three unmet needs (n = 120), 18.6% (n = 42) had three up to six unmet needs, and 4.0% (n = 9) had more than six unmet needs., Discussion: Our results underline the importance of a comprehensive needs assessment for family dementia caregivers to develop and implement concepts that can provide family dementia caregivers with optimal support.

The German congress for healthcare research reached a new historic record of 859 participants from healthcare research, practice, and policy who visited the congress from 4-6 October 2017 to discuss developments, results, and innovations in healthcare research.The German healthcare system will face key challenges over the coming years. As the German population is getting older and disease incidence will become more complex, the number of healthcare professionals will simultaneously decrease.The experts provided solutions and innovations in 322 lectures and in 239 poster presentations.Hot topics included innovative and cross-sectoral healthcare concepts, patient safety, new forms of division of labor, telemedicine, eHealth as well as projects of the innovation fund and the Federal Ministry for Education and Research.Healthcare experts state that healthcare research is a key partner of patients, health policy, and self-government. The experts declare that future healthcare should be regional, cross-sectoral, and should include all healthcare professions. They formulate several demands on health policy for the new legislative period.

The objectives of this cross-sectional analysis were to determine healthcare resource utilization and cost for community-dwelling patients with dementia (PWD) from a payer's and societal perspective, and to analyze the associations between costs and sociodemographic and clinical variables. Analysis of healthcare costs from a payer's perspective was based on a sample of 425 PWD, analysis of healthcare costs from societal perspective on a subsample of 254 PWD and their informal caregivers. Frequency of healthcare resource utilization was assessed by means of questionnaires. Informal care and productivity losses were assessed by using the Resource Utilization in Dementia questionnaire (RUD). Costs were monetarized using standardized unit costs. To analyze the associations, multiple linear regression models were used. Total annual costs per PWD valued 7016€ from a payer's and 25,877€ from a societal perspective, meaning that societal cost is approximately three and a half times as much as payer's expenditures. Costs valuated 5456 € for medical treatments, 1559 € for formal care, 18,327€ for informal care. Productivity losses valued 1297€ for PWD caregivers. Informal care could vary substantially (-21%; +33%) concerning different valuation methods. Medical care costs decreased significantly with progression of dementia and with age. Costs of care double over the stages of dementia. Formal care costs were significantly higher for PWD living alone and informal care costs significantly lower for PWD with an employed caregiver. For all cost categories, deficits in daily living activities were major cost drivers.

Background: People with dementia (PwD) are at a high risk of hospitalization. Hospitals are often not adequately equipped for PwD and discharges often come unexpected. Therefore, PwD are at a risk of adverse outcomes. However, information about those outcomes is rare but crucial for the development of preventive strategies., Objectives: To conduct a quantitative systematic review and meta-analyses on the impact of a hospitalization on readmission, institutionalization, and mortality in PwD. To identify factors associated with these outcomes., Methods: PubMed, CENTRAL, and ScienceDirect were searched for studies including terms for dementia, hospital, readmission, institutionalization, and mortality. Relevant were assessed by a quality criteria sheet. Results were summarized in a table. Meta-analysis was conducted with Review Manager 5.3., Results: The search yielded 1,108 studies; 20 fulfilled the inclusion criteria and 10 studies were eligible for meta-analyses. The incidence and relative risk (RR) of mortality (RR 1.74 CI95 % 1.50, 2.05) and institutionalization (RR: 2.16 CI95 % 1.31, 3.56) of PwD was significantly higher when compared to people without dementia. Results according to readmission rate were inconsistent. Factors significantly associated with the examined adverse outcomes were severity of dementia, number of medications, and deficits in daily living activities., Conclusion: Hospitalization of PwD lead to adverse outcomes. An improvement in the identification of and care for PwD in the acute setting as well as in after care in the community setting, especially in the interface between both settings, is required to prevent adverse outcomes in hospitalized PwD.

Background: The current guidelines imply that basic medical diagnostics for dementia should be provided by general practitioners in cooperation with other specialists such as neurologists and psychiatrists., Objectives: The aims of this paper were to 1) compare the dementia patients of general practice residents whose care is co-managed by neurology/psychiatry residents with those whose care is not; 2) identify the patient variables associated with the utilization of neurological and psychiatric specialists; and 3) describe the frequency of imaging used for dementia patients in primary care., Methods: The analyses utilized data from 485 individuals who screened positive for dementia in primary care (PWD). Clinical variables and the utilization of specialists were assessed via medical records and face-to-face interviews. The factors associated with the utilization of specialists were assessed using multivariate linear regression and included age, sex, relationship status, cognitive impairment, depression, activities of daily living, and formal diagnosis of dementia., Results: Our results show that 89 out of 485 study participants (18.4%) were referred to specialists 12 months prior to assessment. Of these 89 individuals, 14.6% (n = 13) did not receive imaging diagnostics, while 39.3% (n = 35) received brain imaging by CT scan and 46.1% (n = 41) by MRI. PWD referred to specialists differed from those not referred, in age, relationship status, and the presence of a formal diagnosis. Our multivariate analysis revealed that younger age (OR = 0.95; 95% -confidence interval 0.90-0.99; p = 0.04) and higher functional impairment (OR = 1.15; 95% -confidence interval 1.02-1.30; p = 0.02) were associated with a visit to a specialist., Discussion: Only 1 out of every 4 to 5 individuals who have screened positive for dementia have visited a specialist in psychiatry or neurology. While in general, women utilized specialists less often than men, younger and more functionally impaired patients were more likely to be sent to a specialist by their treating general practitioner. Almost 90% of the patients sent to a specialist received cranial neuroimaging, suggesting high adherence to diagnostic guidelines in specialized care.

Importance: Dementia care management (DCM) can increase the quality of care for people with dementia. Methodologically rigorous clinical trials on DCM are lacking., Objective: To test the effectiveness and safety of DCM in the treatment and care of people with dementia living at home and caregiver burden (when available)., Design, Setting, and Participants: This pragmatic, general practitioner-based, cluster-randomized intervention trial compared the intervention with care as usual at baseline and at 12-month follow-up. Simple 1:1 randomization of general practices in Germany was used. Analyses were intent to treat and per protocol. In total, 6838 patients were screened for dementia (eligibility: 70 years and older and living at home) from January 1, 2012, to March 31, 2016. Overall, 1167 (17.1%) were diagnosed as having dementia, and 634 (9.3%) provided written informed consent to participate., Interventions: Dementia care management was provided for 6 months at the homes of patients with dementia. Dementia care management is a model of collaborative care, defined as a complex intervention aiming to provide optimal treatment and care for patients with dementia and support caregivers using a computer-assisted assessment determining a personalized array of intervention modules and subsequent success monitoring. Dementia care management was targeted at the individual patient level and was conducted by 6 study nurses with dementia care-specific qualifications., Main Outcomes and Measures: Quality of life, caregiver burden, behavioral and psychological symptoms of dementia, pharmacotherapy with antidementia drugs, and use of potentially inappropriate medication., Results: The mean age of 634 patients was 80 years. A total of 407 patients received the intended treatment and were available for primary outcome measurement. Of these patients, 248 (60.9%) were women, and 204 (50.1%) lived alone. Dementia care management significantly decreased behavioral and psychological symptoms of dementia (b = -7.45; 95% CI, -11.08 to -3.81; P < .001) and caregiver burden (b = -0.50; 95% CI, -1.09 to 0.08; P = .045) compared with care as usual. Patients with dementia receiving DCM had an increased chance of receiving antidementia drug treatment (DCM, 114 of 291 [39.2%] vs care as usual, 31 of 116 [26.7%]) after 12 months (odds ratio, 1.97; 95% CI, 0.99 to 3.94; P = .03). Dementia care management significantly increased quality of life (b = 0.08; 95% CI, 0 to 0.17; P = .03) for patients not living alone but did not increase quality of life overall. There was no effect on potentially inappropriate medication (odds ratio, 1.86; 95% CI, 0.62 to 3.62; P = .97)., Conclusions and Relevance: Dementia care management provided by specifically trained nurses is an effective collaborative care model that improves relevant patient- and caregiver-related outcomes in dementia. Implementing DCM in different health care systems should become an active area of research., Trial Registration: clinicaltrials.gov Identifier: NCT01401582.

Background: Dementia is one of the most prevalent diseases in the older population. Various dementia care models have been developed to address patient's healthcare needs. They can be described as "collaborative care" or "person-centered care". Referring to the needs of the workforce working with persons with dementia, a key element is the use of interprofessional education (IPE)., Objective: The purpose of this article is to describe different international collaborative care models to define a minimum standard of healthcare professions for collaborative dementia care in primary care. This helps to identify requirements for IPE to optimize care of people with dementia and to support informal caregivers in the future., Material and Methods: In this article six dementia care models from 4 different countries (Germany, USA, UK and Netherlands) are described and compared regarding aims, interventions and healthcare professionals involved., Results: Care teams are minimally comprised of general practitioners or primary care providers, nurses, and social workers. Additional healthcare disciplines may be involved for specific interventions. Mostly, care team members received specific training but such training did not necessarily incorporate the IPE approach. To ensure successful collaboration of professions, IPE training programs should at least consist of the following core topics: (1) early diagnosis, (2) postdiagnostic support, (3) advanced care planning for patients and caregivers and (4) effective collaborative care., Conclusion: The IPE programs for dementia should be expanded and must be widely implemented in order to assess the impact on collaborative practice. This study will provide the knowledge base for structuring IPE trainings developing educational agendas and adapting existing guidelines to improve collaborative dementia care in the future.

Various markers of radiation-induced DNA damage including DNA oxidation were investigated in peripheral lymphocytes of 23 cancer patients prior to and one week after receiving radiotherapy with a cumulative dose of 54-70 Gy. Exposure to ionizing radiation nonsignificantly increased the ratio 2'deoxy-7-dihydro-8-oxoguanosine/2'deoxyguanosine (8-oxodG/dG) from 1.73 x 10(-5) to 3.33 x 10(-5). Frequencies of micronuclei significantly (p = 0.0003) increased from 6.4 to 38.9 per 1000 cells. The frequency of hypoxanthine-guanine-phosphoribosyltransferase (HPRT) mutant lymphocytes measured as 6-thioguanine resistant variant cells by 5-bromodeoxyuridine labeling, was elevated eight-fold, from 4.7 x 10(-6) to 36.2 x 10(-6) (p = 0.008) after termination of the radiotherapy, thus showing a clear response to the radiation treatment. No correlation between levels of oxidative DNA damage and frequencies of HPRT mutant lymphocytes or micronuclei could be established.

This study set out to analyze biomarkers for genotoxic events, e.g., oxidative DNA damage, chromosomal damage and hprt mutations, among flight personnel, who are known to be occupationally exposed to ionizing radiation of cosmic origin. Twenty-three flight engineers were recruited while ground personnel served as a matched control group. Cumulative radiation doses during flight were calculated on the basis of subjects' flight records assuming an exposure rate of 6 microSv per hour of flight. Oxidative DNA damage in peripheral lymphocytes from flight engineers appeared significantly increased in comparison with controls and was associated with cumulative exposure to cosmic radiation. Frequencies of peripheral lymphocyte chromosome aberrations, micronuclei and hprt mutations appeared also to be increased in flight engineers, but not significantly. It was also observed that DNA damage was higher in flight engineers with a relatively shorter flight history in comparison with flight engineers with higher cumulative exposures to radiation, suggesting adaptation to DNA damage caused by ionizing radiation. DNA repair activities measured as unscheduled DNA synthesis were clearly increased in the higher-exposed subgroup of flight engineers, and appeared significantly correlated with cumulative radiation dose, as well as inversely with oxidative DNA damage. The implications for cancer risk assessment in relation to exposure to cosmic radiation are discussed.

In this study we tested the suitability of the human epithelial lung cell line BEAS-2B for in vitro studies of lung carcinogenesis. The human bronchial epithelial lung cell line BEAS-2B, immortalized with an SV-40/Ad-12 hybrid virus construct, was treated for 24 hours with five different concentrations of the lung carcinogen benzo(a)pyrene (B[a]P) to assess the relationship between DNA adduct levels, cell cycle distribution, micronuclei formation (MN), colony forming efficiency (CFE), and anchorage independent growth (AIG). There appeared to be a strong linear correlation between B[a]P concentration and DNA adduct formation, but no difference in cell cycle distribution was observed after incubation with various concentrations of B[a]P. In the incubation range of 4 to 100 nM B[a]P, the number of DNA adducts was linearly correlated with colony formation in AIG and with the number of cells within individual colonies but not the number of colonies in the CFE test. At higher B[a]P concentrations, the clonal expansion of cells in the CFE and the number of colonies in the AIG declined. Also, the number of micronuclei increased with the formation of DNA adducts. It is concluded that after 24 hours of incubation with 100 nM B[a]P, the formation of BPDE-DNA adducts in the human epithelial lung cells BEAS-2B results in maximal induction of cell transformation. Because of this correlation between DNA adduct formation and lung epithelial cell transformation, the BEAS-2B cells seem suitable for in vitro studies on lung carcinogens.