Does living close to allergenic street trees affect lung function in German adults?

INTRODUCTION: Studies on greenspace and lung function in adults produced divergent results. Some of the adverse findings could be due to long-term exposure to allergenic tree pollen. We investigated whether having more birch trees or more allergenic trees around home is related to worse lung function and whether these exposures confound the association between greenspace and lung function. METHODS: The analytic sample consisted of 874 adults aged 20-44 years at baseline from the German study centers, Erfurt and Hamburg, of the ECRHS cohort study. Spirometric lung function was measured in 1991/92, 2000/01, and 2011/12. We counted trees based on tree registries and classified them into allergenic and non-allergenic. We assessed exposure to greenspace with the normalized difference vegetation index (NDVI), tree cover density, and total number of trees in a 300 m buffer around home. Linear mixed models were used. RESULTS: The forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) were decreased in the presence of more birch trees after adjusting for confounders and co-exposures. For every 10 additional birch trees in a 300 m buffer around home, the average change in FEV1 was -27.6 mL (95% confidence interval (CI): [-58.7, 3.5]). For FVC the average change was -28.2 mL (95% CI: [-62.0, 5.6]). No consistent associations were found for allergenic trees, total trees, tree cover density, or NDVI. Unlike other associations, those of birch trees with FEV1 and FVC were not moderated by allergic sensitization to birch pollen, history of asthma symptoms or nasal allergies including hay fever, ozone, NO2, or age. DISCUSSION: Living close to birch trees had an adverse long-term association with lung function. That tree registries were limited to street trees prevented us from answering the question of a potential confounding of greenspace effects by allergenic neighborhood trees.

Effects of age on non-communicable disease risk factors among Nepalese adults.

The growing burden of non-communicable diseases (NCDs) and an increase in the prevalence of the underlying risk factors are creating a challenge to health systems in low- and middle-income countries (LMICs). In Nepal, deaths attributable to NCDs have been increasing, as has life expectancy. This poses questions with regards to how age and various risk factors interact in affecting NCDs. We analyzed the effects of age on NCD risk factors, using data from the Nepalese STEPs survey 2019, a nationally representative cross-sectional study. Six sociodemographic determinants, four behavioral risk factors, and four biological risk factors were examined. Age effects were analyzed among three age groups: below 35 years (young), 35-59 years (middle aged) and 60 years and above (elderly). The prevalence of selected behavioral risk factors for NCDs, notably smoking, alcohol consumption and insufficient physical activity, and some biological risk factors (hypertension, hyperlipidemia) increases with age. The prevalence of most behavioral risk factors was highest among men and women aged 60 years and above. The prevalence of hypertension and hyperlipidemia was highest among the elderly, but the prevalence of diabetes and overweight/obesity was highest among the middle aged for both sexes. Age interactions in the association between behaviors and biological risk factors were surprisingly weak. However, age interactions were significant in the association between alcohol consumption and -hypertension, -overweight/obesity and -hyperlipidemia among women. While the prevalence of NCD risk factors tends to be higher among elders, the interaction between age and risk factors is complex. Most NCD risk factors are related to behaviors, which originate in young adulthood. It is necessary to diagnose and treat biological risk factors, in younger age groups before they manifest as NCDs. Similarly, behavior change interventions need to target these younger age groups to reduce the risk of NCDs later in life.

Health sector readiness for the prevention and control of non-communicable diseases: A multi-method qualitative assessment in Nepal.

In Nepal, deaths attributable to NCDs have increased in recent years. Although NCDs constitute a major public health problem, how best to address this has not received much attention. The objective of this study was to assess the readiness of the Nepalese health sector for the prevention and control of NCDs and their risk factors. The study followed a multi-method qualitative approach, using a review of policy documents, focus group discussions (FGDs), and in-depth interviews (IDIs) conducted between August and December 2020. The policy review was performed across four policy categories. FGDs were undertaken with different cadres of health workers and IDIs with policy makers, program managers and service providers. We performed content analysis using the WHO health system building blocks framework as the main categories. Policy documents were concerned with the growing NCD burden, but neglect the control of risk factors. FGDs and IDIs reveal significant perceived weaknesses in each of the six building blocks. According to study participants, existing services were focused on curative rather than preventive interventions. Poor retention of all health workers in rural locations, and of skilled health workers in urban locations led to the health workers across all levels being overburdened. Inadequate quantity and quality of health commodities for NCDs emerged as an important logistics issue. Monitoring and reporting for NCDs and their risk factors was found to be largely absent. Program decisions regarding NCDs did not use the available evidence. The limited budget dedicated to NCDs is being allocated to curative services. The engagement of non-health sectors with the prevention and control of NCDs remained largely neglected. There is a need to redirect health sector priorities towards NCD risk factors, notably to promote healthy diets and physical activity and to limit tobacco and alcohol consumption, at policy as well as community levels.

Impact of cumulative body mass index and cardiometabolic diseases on survival among patients with colorectal and breast cancer: a multi-centre cohort study.

BACKGROUND: Body mass index (BMI) and cardiometabolic comorbidities such as cardiovascular disease and type 2 diabetes have been studied as negative prognostic factors in cancer survival, but possible dependencies in the mechanisms underlying these associations remain largely unexplored. We analysed these associations in colorectal and breast cancer patients. METHODS: Based on repeated BMI assessments of cancer-free participants from four European countries in the European Prospective Investigation into Cancer and nutrition (EPIC) study, individual BMI-trajectories reflecting predicted mean BMI between ages 20 to 50 years were estimated using a growth curve model. Participants with incident colorectal or breast cancer after the age of 50 years were included in the survival analysis to study the prognostic effect of mean BMI and cardiometabolic diseases (CMD) prior to cancer. CMD were defined as one or more chronic conditions among stroke, myocardial infarction, and type 2 diabetes. Hazard ratios (HRs) and confidence intervals (CIs) of mean BMI and CMD were derived using multivariable-adjusted Cox proportional hazard regression for mean BMI and CMD separately and both exposures combined, in subgroups of localised and advanced disease. RESULTS: In the total cohort of 159,045 participants, there were 1,045 and 1,620 eligible patients of colorectal and breast cancer. In colorectal cancer patients, a higher BMI (by 1 kg/m2) was associated with a 6% increase in risk of death (95% CI of HR: 1.02-1.10). The HR for CMD was 1.25 (95% CI: 0.97-1.61). The associations for both exposures were stronger in patients with localised colorectal cancer. In breast cancer patients, a higher BMI was associated with a 4% increase in risk of death (95% CI: 1.00-1.08). CMDs were associated with a 46% increase in risk of death (95% CI: 1.01-2.09). The estimates and CIs for BMI remained similar after adjustment for CMD and vice versa. CONCLUSIONS: Our results suggest that cumulative exposure to higher BMI during early to mid-adulthood was associated with poorer survival in patients with breast and colorectal cancer, independent of CMD prior to cancer diagnosis. The association between a CMD diagnosis prior to cancer and survival in patients with breast and colorectal cancer was independent of BMI.

BreathEase: rationale, design and recruitment of a randomised trial and embedded mixed-methods study of a multiprofessional breathlessness service in early palliative care.

BACKGROUND: The Munich Breathlessness Service has adapted novel support services to the German context, to reduce burden in patients and carers from breathlessness in advanced disease. It has been evaluated in a pragmatic fast-track randomised controlled trial (BreathEase; NCT02622412) with embedded qualitative interviews and postal survey. The aim of this article is to describe the intervention model and study design, analyse recruitment to the trial and compare sample characteristics with other studies in the field. METHODS: Analysis of recruitment pathways and enrolment, sociodemographic and clinical characteristics of participants and carers. RESULTS: Out of 439 people screened, 253 (58%) were offered enrolment and 183 (42%) participated. n=97 (70%) carers participated. 186 (42%) people did not qualify for inclusion, mostly because breathlessness could not be attributed to an underlying disease. All participants were self-referring; 60% through media sources. Eligibility and willingness to participate were associated to social networks and illness-related activities as recruitment routes. Mean age of participants was 71 years (51% women), with COPD (63%), chronic heart failure (8%), interstitial lung disease (9%), pulmonary hypertension (6%) and cancer (7%) as underlying conditions. Postal survey response rate was 89%. Qualitative interviews were conducted with 16 patients and nine carers. CONCLUSION: The BreathEase study has a larger and more heterogeneous sample compared to other trials. The self-referral-based and prolonged recruitment drawing on media sources approximates real-world conditions of early palliative care. Integrating qualitative and quantitative components will allow a better understanding and interpretation of the results of the main effectiveness study.

Excess Risk of Lung Cancer Among Agriculture and Construction Workers in Indonesia.

Background: In Indonesia, many occupations and industries involve a variety of hazardous and toxic materials. The ILO estimates that about 21.1% of the tracheal, bronchial, and lung cancer deaths among men were attributable to workplace hazardous substances. This study investigated the relationship between occupations or workplace exposure and the risk of lung cancer in the country. The results will help determine how Indonesia can best mitigate the risk for its workers. Objectives: This case-control study utilizes the Indonesian Standard of Industrial Classification (IndSIC) 2015 with the aim of exploring the risk of lung cancer among Indonesian workers. Methods: The study included patients aged 35 years old or older receiving thoracic CT at the radiology department of Persahabatan Hospital. The cases were histological-confirmed primary lung cancers, while the controls were negative thoracic CT scan for lung cancer. The subjects' job titles and industries were classified according to IndSIC 2015 and blind to the patient's grouping as a case or control. Logistic regression was used to determine the odds ratios for lung cancer among all sections and some divisions or groups of IndSIC 2015. Findings: The mean age was 58.1 (±10.23) years for lung cancer patients and 54.5 (±10.23) years for controls. The majority of subjects (19.6%) worked in Section G (Wholesale and retail trade; repair of motor vehicles and motorcycle). After adjusting for age, gender, level of education, and smoking habit, the risk of lung cancer was nearly three-times higher (OR = 2.8, 95% CI = 1.11-7.02) in workers of Division A01 (crop, animal production, and hunting) and two-times higher (OR = 1.9, 95% CI = 1.05-3.46) in workers of Section F (construction) compared to the workers in other sections or divisions. Conclusions: The excess risk of lung cancer among certain categories of workers confirms the need for improved policy, monitoring, and control of occupational exposure for primary cancer prevention and workers' compensation purposes.

Effectiveness of a specialised breathlessness service for patients with advanced disease in Germany: a pragmatic fast-track randomised controlled trial (BreathEase).

BACKGROUND: The effectiveness of the Munich Breathlessness Service (MBS), integrating palliative care, respiratory medicine and physiotherapy, was tested in the BreathEase trial in patients with chronic breathlessness in advanced disease and their carers. METHODS: BreathEase was a single-blinded randomised controlled fast-track trial. The MBS was attended for 5-6 weeks; the control group started the MBS after 8 weeks of standard care. Randomisation was stratified by cancer and the presence of a carer. Primary outcomes were patients' mastery of breathlessness (Chronic Respiratory Disease Questionnaire (CRQ) Mastery), quality of life (CRQ QoL), symptom burden (Integrated Palliative care Outcome Scale (IPOS)) and carer burden (Zarit Burden Interview (ZBI)). Intention-to-treat (ITT) analyses were conducted with hierarchical testing. Effectiveness was investigated by linear regression on change scores, adjusting for baseline scores and stratification variables. Missing values were handled with multiple imputation. RESULTS: 92 patients were randomised to the intervention group and 91 patients were randomised to the control group. Before the follow-up assessment after 8 weeks (T1), 17 and five patients dropped out from the intervention and control groups, respectively. Significant improvements in CRQ Mastery of 0.367 (95% CI 0.065-0.669) and CRQ QoL of 0.226 (95% CI 0.012-0.440) score units at T1 in favour of the intervention group were seen in the ITT analyses (n=183), but not in IPOS. Exploratory testing showed nonsignificant improvements in ZBI. CONCLUSIONS: These findings demonstrate positive effects of the MBS in reducing burden caused by chronic breathlessness in advanced illness across a wide range of patients. Further evaluation in subgroups of patients and with a longitudinal perspective is needed.

[Online-based, qualified second opinion for patients with colorectal cancer - A pilot study of the Felix Burda Foundation in co-operation with the Network against Colorectal Cancer]. / Onlinebasierte, qualifizierte Zweitmeinung für Patienten mit kolorektalem Karzinom ­ eine Pilotstudie der Felix Burda Stiftung in Zusammenarbeit mit dem Netzwerk gegen Darmkrebs.

BACKGROUND: Modern, individualised therapies can improve the survival of patients with colorectal cancer. However, not all patients are referred for treatment to a certified colorectal cancer centre, where a tumor board supports the implementation of their therapy in accordance to guidelines. This study examines the feasibility and demand of a structured, online-based, qualified second opinion for patients with colorectal cancer. METHOD: A 15-month pilot study between 2009 and 2011, offered patients with colorectal cancer to obtain a qualified second opinion of a tumour board based on an electronic patient record completed online with the assistance of a case manager. Life-satisfaction levels and quality of life (EORCT QLQ-C30) of the participants has been monitored for a year. RESULTS: In 95 % of the cases, a complete electronic patient record and a second opinion could be generated. Less than half of the participants received their first therapy recommendation from a clinic with a tumour board. The second opinion confirmed the initial medical opinion in 40 % of the cases - 33 % showed a partial and 27 % showed a significant deviation. In case of a deviation, the implementation of the second opinion improved the patients' quality of life. CONCLUSION: Generating an online-based, qualified second opinion by an interdisciplinary tumour board is technically and logistically well feasible. The online-based second opinion could significantly improve the quality of treatment for patients with colorectal cancer in the future and thus improve their quality of life.

Regional differences in medical needs and care for skin cancer across Bavaria: confronting the gap.

BACKGROUND: The management of keratinocyte carcinoma (KC) and actinic keratosis (AK) as well as the number of dermatologists differ across the Bavarian counties in Germany. OBJECTIVES: To determine regions with low utilization rates of dermatological care and a high medical need due to AK and KC burden. MATERIALS AND METHODS: A cross-sectional study of 2,483 people was carried out during the Munich Oktoberfest in September 2016. Participants from urban, semi-urban and rural areas completed a questionnaire and received a medical examination on site by dermatologists. RESULTS: The rate of previous skin cancer screening and previous treatment by dermatologists ranged from 18.8% to 58.6% and from 34.3% to 75.4% for all regions, respectively. Over 60% of people living in the environs or rural areas would consult a dermatologist first if they found a visible skin condition. Thus, people living in urban areas were twice as likely as people living in rural areas to consult a dermatologist first (odds ratio = 2.16; 95% CI: 1.38-3.39). Comparing the three different locations, dermatologists detected the highest AK burden among people living in rural areas (27.3% of the participants) and the highest KC burden among people living in urban areas (3.4% of the participants). CONCLUSION: In rural areas, a high AK burden coupled with a low utilization rate of dermatological care was observed. To effectively address these problems, a broader implementation of alternative medical resources, such as teledermatology, might improve access to health care.

Asbestos-Related Lung Cancer: A Hospital-Based Case-Control Study in Indonesia.

Indonesia has limited data on asbestos-related diseases despite abundant use. This study investigated the risk of occupational asbestos exposure for lung cancer development, utilizing a hospital-based case-control study. Subjects were patients who received a thoracic CT scan at Persahabatan Hospital, Jakarta. The cases had primary lung cancer confirmed by histology, the controls were negative for lung cancer. The cumulative occupational asbestos exposure was calculated by multiplying the exposure intensity by the years of exposure. The exposure intensity was obtained by adopting the weighted arithmetic mean value of asbestos exposure from a job-exposure matrix developed in Korea. The primary data analysis was based on logistic regression. The study included 696 subjects, with 336 cases and 360 controls. The chance of lung cancer for subjects exposed to asbestos was doubled (OR = 2.04, 95% CI = 1.21-3.42) compared with unexposed, and subjects with a cumulative asbestos exposure of 10 fiber-years or more even showed an OR of 3.08 (95% CI = 1.01-9.46). The OR of the combined effect between smoking and asbestos was 8.7 (95% CI = 1.71-44.39); the interaction was consistent with an additive and multiplicative risk model. Asbestos exposure is associated with a higher chance of lung cancer. Improved policies are needed to protect the population from asbestos hazards.

Ageing Investigation Using Two-Time-Point Metabolomics Data from KORA and CARLA Studies.

Ageing, one of the largest risk factors for many complex diseases, is highly interconnected to metabolic processes. Investigating the changes in metabolite concentration during ageing among healthy individuals offers us unique insights to healthy ageing. We aim to identify ageing-associated metabolites that are independent from chronological age to deepen our understanding of the long-term changes in metabolites upon ageing. Sex-stratified longitudinal analyses were performed using fasting serum samples of 590 healthy KORA individuals (317 women and 273 men) who participated in both baseline (KORA S4) and seven-year follow-up (KORA F4) studies. Replication was conducted using serum samples of 386 healthy CARLA participants (195 women and 191 men) in both baseline (CARLA-0) and four-year follow-up (CARLA-1) studies. Generalized estimation equation models were performed on each metabolite to identify ageing-associated metabolites after adjusting for baseline chronological age, body mass index, physical activity, smoking status, alcohol intake and systolic blood pressure. Literature researches were conducted to understand their biochemical relevance. Out of 122 metabolites analysed, we identified and replicated five (C18, arginine, ornithine, serine and tyrosine) and four (arginine, ornithine, PC aa C36:3 and PC ae C40:5) significant metabolites in women and men respectively. Arginine decreased, while ornithine increased in both sexes. These metabolites are involved in several ageing processes: apoptosis, mitochondrial dysfunction, inflammation, lipid metabolism, autophagy and oxidative stress resistance. The study reveals several significant ageing-associated metabolite changes with two-time-point measurements on healthy individuals. Larger studies are required to confirm our findings.

Risk and potential risk reduction in diabetes type 2 patients in Germany.

Avoiding serious complications such as stroke, myocardial infarction, and amputations in diabetes patients is the main interest of long-term treatment. Given the considerable prevalence of diabetes type 2 in industrialized countries this is a major public health concern as well as a burden to health care systems. The present study estimated the current risk of major complications occurring in the German diabetes type 2 population and explored the potential for further risk reduction. Risk reduction can be achieved when physiological and behavioral parameters (HbAlc, blood pressure, cholesterol level, body mass index, smoking) are set to target values recommended in guidelines. To estimate individual risk and potential risk reduction the multifactor disease model Mellibase was employed. Data were obtained from the German Health Survey of 1998, which includes a sample of 7,124 individuals representative of the German population. The survey shows a prevalence rate of 6.3% for diabetes type 2 in persons older than 35 years. The analyses reveal that the overall potential for risk reduction is moderate (e.g., the average reduction potential of the 10-year risk of stroke is 5.7%). A majority of parameter ranges found in the patient population are either already close to the recommended values (HbA1c), are not alarmingly higher than in the general population (blood pressure) or have little impact on risk reduction. In addition nonmodifiable risk factors such as duration of the illness and advanced age constrain possible improvements. However, there is a wide variation in the actual risk between individuals (e.g., the 10-year risk of stroke varies between 2.2% and 79.8%), and thus a wide variation in potential risk reduction (the risk reduction potential for stroke varies between 0% and 53.4%). Intensified treatment should therefore (a) focus on relevant subgroups of patients taking their risk reduction potential into account and (b) aim at improvement in the overall metabolic profile rather than concentrating on single risk factors.

Dynamic Cox modelling based on fractional polynomials: time-variations in gastric cancer prognosis.

The most popular model used for survival analysis is the proportional hazards regression model proposed by Cox. This is mainly due to its exceptional simplicity. Nevertheless the fundamental assumption of the Cox model is the proportionality of the hazards. For many applications, however, this assumption is doubtful. Proposals to extend the Cox model for non-proportional hazards to allow for dynamic effect structures usually either depend on prespecifications or require non-standard estimation techniques and are thus not favoured in application. Moreover, tests to verify the dynamic effect structures are not straightforward or lack omnibus power. In this paper we propose a flexible method for modelling dynamic effects in survival data within the Cox framework. The method is based on fractional polynomials as introduced by Royston and Altman. This allows for a transformation of the dynamic predictor which leads back to the conventional Cox model and hence fitting is straightforward using standard estimation techniques. In addition, it offers the possibility of easily verifying the existence of time-variation. We describe a model selection algorithm which selects time-varying effects only when evidence is given in the data. We illustrate the properties of the approach in a simulation study and compare it with other methods. In a survival study of gastric cancer patients, we apply the approach to analyse dynamic structures in the effects of prognostic factors.

Y-box factor YB-1 predicts drug resistance and patient outcome in breast cancer independent of clinically relevant tumor biologic factors HER2, uPA and PAI-1.

Intrinsic or acquired resistance to chemotherapy is responsible for failure of current treatment regimens in breast cancer patients. The Y-box protein YB-1 regulates expression of the P-glycoprotein gene mdr1, which plays a major role in the development of a multidrug-resistant tumor phenotype. In human breast cancer, overexpression and nuclear localization of YB-1 is associated with upregulation of P-glycoprotein. In our pilot study, we analyzed the clinical relevance of YB-1 expression in breast cancer (n = 83) after a median follow-up of 61 months and compared it with tumor-biologic factors already used for clinical risk-group discrimination, i.e., HER2, urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1). High YB-1 expression in tumor tissue and surrounding benign breast epithelial cells was significantly associated with poor patient outcome. In patients who received postoperative chemotherapy, the 5-year relapse rate was 66% in patients with high YB-1 expression. In contrast, in patients with low YB-1 expressions, no relapse has been observed so far. YB-1 expression thus indicates clinical drug resistance in breast cancer. Moreover, YB-1 correlates with breast cancer aggressiveness: in patients not treated with postoperative chemotherapy, those with low YB-1 expression are still free of disease, whereas the 5-year relapse rate in those with high YB-1 was 30%. There was no significant correlation between YB-1 expression and either HER2 expression or uPA and PAI-1 levels. Risk-group assessment achieved by YB-1 differed significantly from that by HER2 or uPA/PAI-1. In conclusion, YB-1 demonstrated prognostic and predictive significance in breast cancer by identifying high-risk patients in both the presence and absence of postoperative chemotherapy, independent of tumor-biologic factors currently available for clinical decision making.