Impact of COVID-19 immunisation on COVID-19 incidence, hospitalisations, and deaths by age group in Germany from December 2020 to October 2021.

BACKGROUND: Utilising national surveillance data, we investigated the impact of the COVID-19 immunisation campaign on COVID-19 morbidity and mortality between December/2020 and October/2021 in Germany. METHODS: We compared patterns in immunisation coverage, incidence, hospitalisations, and deaths among 12-17, 18-59, and 60+ year-olds and examined these patterns within the context of anti-pandemic measures. RESULTS: COVID-19 incidence increased in all age groups following the end of lockdown restrictions in March/2021, but as Germany experienced successive peaks in incidence, age groups with higher immunisation coverage experienced successively smaller peaks. Notwithstanding corresponding increases during periods of higher incidence, among those aged 60+ years, COVID-19 related hospitalisations and deaths declined considerably as immunisation coverage increased, despite circulation of virus variants known to cause more severe illness. CONCLUSION: Although ecological in nature, this study allows us to demonstrate clear patterns of decline in COVID-19 morbidity and mortality in Germany during the course of the immunisation campaign.

SARS-CoV-2 outbreaks in hospitals and long-term care facilities in Germany: a national observational study.

BACKGROUND: Outbreaks of coronavirus disease (COVID-19) in hospitals and long-term care facilities (LTCFs) pose serious public health threats. We analysed how frequency and size of SARS-CoV-2 outbreaks in hospitals and LTCFs have altered since the beginning of the pandemic, in particular since the start of the vaccination campaign. METHODS: We used mandatory notification data on SARS-CoV-2 cases in Germany and stratified by outbreak cases in hospitals and LTCFs. German vaccination coverage data were analysed. We studied the association of the occurrence of SARS-CoV-2 outbreaks and outbreak cases with SARS-CoV-2 cases in Germany throughout the four pandemic waves. We built also counterfactual scenarios with the first pandemic wave as the baseline. FINDINGS: By 21 September 2021, there were 4,147,387 SARS-CoV-2 notified cases since March 2020. About 20% of these cases were reported as being related to an outbreak, with 1% of the cases in hospitals and 4% in LTCFs. The median number of outbreak cases in the different phases was smaller (≤5) in hospitals than in LTCFs (>10). In the first and second pandemic waves, we observed strong associations in both facility types between SARS-CoV-2 outbreak cases and total number of notified SARS-CoV-2 cases. However, during the third pandemic wave we observed a decline in outbreak cases in both facility types and only a weak association between outbreak cases and all cases. INTERPRETATION: The vaccination campaign and non-pharmaceutical interventions have been able to protect vulnerable risk groups in hospitals and LTCFs. FUNDING: No specific funding.

Monitoring of Influenza Vaccination Coverage among Pregnant Women in Germany Based on Nationwide Outpatient Claims Data: Findings for Seasons 2014/15 to 2019/20.

Pregnant women and their infants are at increased risk for severe influenza-related complications. A decade has passed since influenza vaccination was first recommended for pregnant women in Germany in 2010; however, monitoring of vaccination coverage (VC) has not yet been implemented for this target group. Using nationwide outpatient claims data, we here provide results on influenza VC among pregnant women in Germany for seasons 2014/15 to 2019/20. For any given season, pregnant women were defined as women who had undergone prenatal health care in at least two consecutive quarters within a season. VC increased from 9.0% in season 2014/15 to 16.6% in 2019/20 (+84%), while most of the increase occurred from season 2016/17 (VC: 9.9%) onwards (+68%). Consistently across seasons, women in east Germany were 40 to 60% more likely to be vaccinated compared to women residing in west Germany. According to age, the highest VC was observed among women aged 35 to <40 years (2019/20: 18.2%). Despite noticeable increases in influenza VC during recent years, overall coverage remains low among pregnant women. Starting with this analysis, VC among pregnant women in Germany will be monitored on a yearly basis in order to detect trends and identify immunization gaps.

Utilization of influenza vaccination among chronically ill individuals in Germany: A nationwide claims-based analysis.

BACKGROUND: Individuals with chronic diseases have a higher risk of serious complications or even death in case of influenza infection. The European Union (EU) set a goal to reach a vaccination coverage of 75% in seniors and chronically ill individuals. The aim of this study was to assess influenza vaccination uptake among individuals with a wide spectrum of chronic diseases and examine its regional variations and temporal trends over a period of the last ten years. METHODS: We used nationwide SHI-physician outpatient claims data from the years 2009 to 2018 covering 87% of the total German population to assess influenza vaccination uptake among individuals over 1 year of age with at least one of the following chronic diseases: pulmonary, cardiovascular, liver, kidney, metabolic, neurological and musculoskeletal diseases, as well as immune deficiency disorders, including HIV infection. RESULTS: Influenza vaccination coverage varied across patient populations between 19% (multiple sclerosis) and 44% (chronic kidney disease) in the influenza season 2017/18. Vaccination coverage was slightly higher among females than males, except for HIV/AIDS patients. Among HIV-patients vaccination coverage was higher by 7 percent points among males (43%) than females (37%). The coverage was higher nearly for all patient groups in the eastern than western federal states. Over the observation period vaccination uptake showed decreasing trends in most of the target groups. Among patients with HIV/AIDS and immune deficiency disorders a stagnating trend was observed. CONCLUSIONS: Vaccination uptake among chronically ill individuals is suboptimal and far from the EU-defined target of 75%. There were substantial variations in coverage by disease groups, individual factors and regions. The disease-specific evaluation of the current study allows identification of populations at higher risk with considerable vaccination gaps. Further efforts are needed to improve vaccination uptake in these vulnerable population groups.

The Decline in Outpatient Antibiotic Use.

BACKGROUND: A central component of the German antibiotic resistance strategy is to monitor the outpatient prescribing of systemic antibiotics nationwide, across all of the statutory health-insurance providers, in order to provide a basis for targeted quality-assurance measures. METHODS: All outpatient drug prescription data from patients covered by the statutory health-insurance carriers in Germany in the age groups 0-14, 15-64, and ≥ 65 years were assessed. The chosen primary outcome measure under study was the prescription rate (number of antibiotic prescriptions per 1000 insurees per year) for the years 2010 to 2018. RESULTS: Over the period of the study, a 21% decline was seen in the use of systemic antibiotics in outpatients, from 562 to 446 prescriptions per 1000 insurees per year in 2010 and 2018, respectively. The most marked reduction in the prescription rate-by 41%-was seen among child and adolescent insurees (in other age groups: -17% among those aged 15-64, -12% among those aged 65 and older). A downward trend was seen in all regions of Germany, and for most of the active substance groups for which data were obtained. In 2018, the prescription rate varied by a factor of 1.8 among regions, with the highest rate in the Saarland (572 per 1000 insurees per year) and the lowest in Brandenburg (318 per 1000 insurees per year). CONCLUSION: The observed nationwide decline in the prescription of antibiotics to outpatients in all age groups may be a result of the numerous initiatives that have been put into action to reinforce the appropriate use of antibiotics in Germany. A change in pediatric prescribing practices is demonstrated by the marked reduction in this age group. The remaining major differences across German regions underscore the importance of regionally tailored programs for the promotion of rational antibiotic use.

Comorbidity profile of patients with concurrent diagnoses of asthma and COPD in Germany.

The aim of this study was to estimate the prevalence of concurrent diagnoses of asthma/COPD and examine its full spectrum of comorbid disorders in Germany. We used nationwide outpatient claims data comprising diagnoses of all statutory health insurees (40+ years) in 2017 (N = 40,477,745). The ICD-10 codes J44 (COPD) and J45 (asthma) were used to identify patients. The odds of 1,060 comorbid disorders were examined in a case-control study design. Of all insurees, 4,632,295 (11%) were diagnosed with either asthma or COPD. Of them, 43% had asthma only, 44% COPD only and 13% both diseases. The prevalence of concurrent asthma/COPD was 1.5% with a slightly higher estimate among females than males (1.6% vs. 1.4%) and constant increase by age in both sexes. Comorbid disorders were very common among these patients. 31 disorders were associated with a strong effect size (odds ratio > 10), including other respiratory diseases, but also bacterial (e.g., mycobacteria, including tuberculosis) and fungal infections (e.g., sporotrichosis and aspergillosis). Patients with concurrent asthma/COPD suffer from comorbid disorders involving various body systems, which points to the need of a multidisciplinary care approach. Regular screening for common comorbid disorders may result in better clinical course and prognosis as well as improvement of patients' quality of life.

Marked reductions in outpatient antibiotic prescriptions for children and adolescents - a population-based study covering 83% of the paediatric population, Germany, 2010 to 2018.

BackgroundPrescribing of systemic antibiotics in general and of cephalosporins in particular in German paediatric outpatients has previously been reported to be higher than in other European countries.AimOur objective was to assess recent trends in antibiotic prescribing in German children.MethodsThis study was conducted as consecutive annual cross-sectional analyses and included all children aged 0-14 years (n = 9,389,183 in 2018) covered by statutory health insurance in Germany. Annual antibiotic prescription rates from 2010 to 2018 were calculated for the age groups 0-1, 2-5, 6-9 and 10-14 years. Poisson regression was used to estimate trends of prescription rates by age group and antibiotic subgroup.ResultsOverall, the age-standardised antibiotic prescription rate decreased significantly by 43% from 746 prescriptions per 1,000 persons in 2010 to 428 per 1,000 in 2018 (p < 0.001). Reductions were most pronounced in the age groups 0-1 year (-50%) and 2-5 years (-44%). The age group 2-5 years exhibited the highest prescription rate with 683 per 1,000 in 2018 (0-1 year: 320/1,000; 6-9 years: 417/1,000; 10-14 years: 273/1,000). Cephalosporins (second and third generation) accounted for 32% of prescribed antibiotics.ConclusionsMarked reductions in antibiotic prescribing during the last decade indicate a change towards more judicious paediatric prescribing habits. Compared with other European countries, however, prescribing of second- and third-generation cephalosporins remains high in Germany, suggesting frequent first-line use of these substances for common respiratory infections. Considerable regional variations underline the need for regionally targeted interventions.

Trends in prevalence of depression in Germany between 2009 and 2017 based on nationwide ambulatory claims data.

BACKGROUND: Studies based on health insurance funds unanimously indicate a rise in administrative prevalence of depression, while population surveys with standardized diagnostic procedures do not. We describe recent trends in the prevalence of depressive disorders as diagnosed in routine care from 2009-2017 in Germany. METHODS: We used nationwide ambulatory claims data from all residents with statutory health insurance, covering 87% of the total population. Cases were defined as persons with at least one documented diagnosis of depression (ICD-10-GM codes: F32, F33 or F34.1). The administrative prevalence was computed for each year according to age, sex, degree of urbanization and severity of depression diagnosis. RESULTS: The prevalence increased from 12.5% in 2009 to 15.7% in 2017 (+26%). Overall, women were twice as likely as men to receive a diagnosis, although the prevalence increased more strongly in men compared to women (+40% vs. +20%). Age- and sex-stratified analyses revealed the highest prevalence increase in adolescents and young men at the ages of 15-19 years (+95%) and 20-25 years (+72%). Rural areas with a low population density showed the highest rise in administrative prevalence (+34%), while big urban municipalities showed the lowest (+25%). LIMITATIONS: Administrative claims data rely on diagnoses coded for billing purposes and thus depend on coding practice as well as patients' help seeking behavior. CONCLUSIONS: Depressive disorders are of increasing importance in ambulatory health care in Germany. Parts of the increase may be attributed to changing cultural constructions of mental health along with the expansion of mental health care supply.

Mental and somatic comorbidity of depression: a comprehensive cross-sectional analysis of 202 diagnosis groups using German nationwide ambulatory claims data.

BACKGROUND: Depression is frequently accompanied by other mental disorders and various somatic diseases; however, previous comorbidity studies often relied on self-reported data and have not simultaneously assessed the entire spectrum of mental and somatic diagnoses. The aim is to provide a complete picture of mental and somatic comorbidity of depression in routine outpatient care in a high income country with a relatively well equipped health care system. METHODS: Using ambulatory claims data covering 87% of the German population (age 15+), we designed a cross-sectional study by identifying persons diagnosed with mild, moderate and severe depression in 2017 (N = 6.3 million) and a control group matched 4:1 on sex, 5-year age group and region of residence (N = 25.2 million). Stratified by severity, we calculated the prevalence of 202 diagnosis groups included in the ICD-10 in persons with depression as compared to matched controls using prevalence ratios (PR). RESULTS: Nearly all mental disorders were at least twice as prevalent in persons with depression relative to controls, showing a dose-response relationship with depression severity. Irrespective of severity, the three most prevalent somatic comorbid diagnosis groups were 'other dorsopathies' (M50-M54), 'hypertensive diseases' (I10-I15) and 'metabolic disorders' (E70-E90), exhibiting PRs in moderate depression of 1.56, 1.23 and 1.33, respectively. Strong associations were revealed with diseases of the central nervous system (i.e. multiple sclerosis) and several neurological diseases, among them sleep disorders, migraine and epilepsy, most of them exhibiting at least 2- to 3-fold higher prevalences in depression relative to controls. Utilization of health care was higher among depression cases compared to controls. CONCLUSIONS: The present study based on data from nearly the complete adolescent and adult population in Germany comprehensively illustrates the comorbidity status of persons diagnosed with depression as coded in routine health care. Our study should contribute to increasing the awareness of the strong interconnection of depression with all other mental and the vast majority of somatic diseases. Our findings underscore clinical and health-economic relevance and the necessity of systematically addressing the high comorbidity of depression and somatic as well as other mental diseases through prevention, early identification and adequate management of depressive symptoms.

Trends and regional distribution of outpatient claims for asthma, 2009-2016, Germany.

OBJECTIVE: To investigate asthma morbidity in Germany by calculating current prevalence, examining its temporal and spatial trends and estimating the total number of asthmatics in Germany and calculating age-, sex- and residence-specific risk. METHODS: We used claims data reported by physicians during 2009-2016, including outpatient diagnoses of all statutory health insured individuals, comprising 85.3% (70 416 019/82 521 653) of the total population in Germany in 2016. We performed a spatial analysis of asthma prevalence according to administrative district by calculating Global and Local Moran's I. We assessed the risk of asthma by sex, age, type of residence (rural versus urban) and federal state (East versus West) using a multilevel parametric survival regression. FINDINGS: We estimated that 4.7 million individuals were affected by asthma in 2016, including 0.8 million children and 3.9 million adults. We observed a slightly higher prevalence (with an increasing trend) among adults (5.85%; 3 408 622/58 246 299) compared to children (5.13%; 624 899/12 169 720), and calculated an age-standardized prevalence of 5.76% (95% confidence interval, CI: 5.76-5.77). We found evidence of a strong spatial autocorrelation (Global Moran's I: 0.50, P < 0.0001), and identified local spatial clusters with higher levels of prevalence. Living in the western (versus eastern) federal states and living in densely populated large urban municipalities (versus rural area) were independently associated with an increased risk of asthma, with hazard ratios of 1.33 (95% CI: 1.32-1.34) and 1.32 (95% CI: 1.31-1.32), respectively. CONCLUSION: Our insights into the spatial distribution of asthma morbidity may inform public health interventions, including region-specific prevention programmes and control.

Higher prevalence of heart failure in rural regions: a population-based study covering 87% of German inhabitants.

BACKGROUND: So far the extent of regional variation of heart failure (HF) prevalence in Germany is unknown. METHODS: Using a full sample of nationwide claims data covering ambulatory care of approximately 87% of the German population, this study aimed to (i) examine regional differences of HF prevalence on the level of 402 German administrative districts and (ii) investigate factors associated with HF prevalence. This study included all statutory health-insured patients aged ≥ 40 years in 2017, comprising about 40 million individuals. Age- and sex-standardized HF prevalence was estimated on the district level. Two-level logistic regression analysis was employed to study the influence of the district-related factors degree of urbanisation and regional socio-economic status on HF diagnosis, adjusted for the individual's age and sex. RESULTS: HF prevalence in 2017 was 6.0%. Standardized prevalence on the district level varied by a factor of 4.3 (range 2.8-11.9%). Regional socio-economic status and degree of urbanisation were independently associated with HF prevalence. The prevalence increased with decreasing degree of urbanisation. The adjusted risk of suffering from HF was 40% higher in 'rural areas with a low population density' as compared to 'big urban municipalities' (odds ratio 1.40, 99% CI 1.24-1.59). CONCLUSION: Strong regional variations in HF prevalence may inform future public health policies regarding targeted resource planning and prevention strategies. High prevalence in areas with low population density adds to the challenge of ensuring universal access to health services in rural German regions.

Patterns of the initiation of disease-modifying antirheumatic drugs in incident rheumatoid arthritis: a German perspective based on nationwide ambulatory drug prescription data.

This study aimed at providing a current and nearly complete picture of the patterns of the initiation of disease-modifying antirheumatic drugs (DMARDs) in patients with newly diagnosed RA. Based on ambulatory drug prescription data and physician billing claims data covering 87% of the German population, we assembled a cohort of incident RA patients aged 15-79 years (n = 54,896) and assessed the prescription frequency of total DMARDs, conventional synthetic (csDMARDs) and biologic DMARDs (bDMARDs) within the first year of disease. Using multiple logistic regression, we estimated the chance of early DMARD receipt based on age, sex, serotype and specialty of prescribing physician while controlling for region of residence. In total, 44% of incident RA patients received a DMARD prescription within the first year of disease. In multiple regression, younger patients (< 35 years) had 1.7-fold higher chances of receiving a csDMARD than patients aged ≥ 65 years [odds ratio (OR): 1.65 with 95% confidence interval (CI) 1.51-1.80] and almost tenfold higher chances to receive a bDMARD [OR (95% CI) 9.5 (8.0-11.3)]. Seropositivity and a visit to a rheumatologist were positively associated with DMARD initiation [OR (95% CI) 2.8 (2.6-2.9) and 5.9 (5.6-6.2) for csDMARDs, respectively]. Based on data covering 87% of the German population, the present study revealed that less than half of incident RA patients receive DMARDs within the first year of disease and that marked differences exist according to age. The study highlights the importance of involving a rheumatologist early in the management of RA.

Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins.

Importance: There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. Objective: To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria. Design, Setting, and Participants: Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS). Main Outcomes and Measures: Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity). Results: In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity of 0.83, based on the US Preventive Services Task Force screening criteria, the sensitivity of the integrated risk prediction (biomarker) model was 0.63 compared with 0.43 for the smoking model. Conversely, at an overall sensitivity of 0.42, based on the US Preventive Services Task Force screening criteria, the integrated risk prediction model yielded a specificity of 0.95 compared with 0.86 for the smoking model. Conclusions and Relevance: This study provided a proof of principle in showing that a panel of circulating protein biomarkers may improve lung cancer risk assessment and may be used to define eligibility for computed tomography screening.

Obesity as risk factor for subtypes of breast cancer: results from a prospective cohort study.

BACKGROUND: Earlier epidemiological studies indicate that associations between obesity and breast cancer risk may not only depend on menopausal status and use of exogenous hormones, but might also differ by tumor subtype. Here, we evaluated whether obesity is differentially associated with the risk of breast tumor subtypes, as defined by 6 immunohistochemical markers (ER, PR, HER2, Ki67, Bcl-2 and p53, separately and combined), in the prospective EPIC-Germany Study (n = 27,012). METHODS: Formalin-fixed and paraffin-embedded (FFPE) tumor tissues of 657 incident breast cancer cases were used for histopathological analyses. Associations between BMI and breast cancer risk across subtypes were evaluated by multivariable Cox regression models stratified by menopausal status and hormone therapy (HT) use. RESULTS: Among postmenopausal non-users of HT, higher BMI was significantly associated with an increased risk of less aggressive, i.e. ER+, PR+, HER2-, Ki67low, Bcl-2+ and p53- tumors (HR per 5 kg/m2: 1.44 [1.10, 1.90], p = 0.009), but not with risk of more aggressive tumor subtypes. Among postmenopausal users of HT, BMI was significantly inversely associated with less aggressive tumors (HR per 5 kg/m2: 0.68 [0.50, 0.94], p = 0.018). Finally, among pre- and perimenopausal women, Cox regression models did not reveal significant linear associations between BMI and risk of any tumor subtype, although analyses by BMI tertiles showed a significantly lower risk of less aggressive tumors for women in the highest tertile (HR: 0.55 [0.33, 0.93]). CONCLUSION: Overall, our results suggest that obesity is related to risk of breast tumors with lower aggressiveness, a finding that requires replication in larger-scale analyses of pooled prospective data.

Effect of Fluid Intake on Hydration Status and Skin Barrier Characteristics in Geriatric Patients: An Explorative Study.

BACKGROUND/AIM: Inadequate fluid intake is assumed to be a trigger of water-loss dehydration, which is a major health risk in aged and geriatric populations. Thus, there is a need to search for easy to use diagnostic tests to identify dehydration. Our overall aim was to investigate whether skin barrier parameters could be used for predicting fluid intake and/or hydration status in geriatric patients. METHODS: An explorative observational comparative study was conducted in a geriatric hospital including patients aged 65 years and older. We measured 3-day fluid intake, skin barrier parameters, Overall Dry Skin Score, serum osmolality, cognitive and functional health, and medications. RESULTS: Forty patients were included (mean age 78.45 years and 65% women) with a mean fluid intake of 1,747 mL/day. 20% of the patients were dehydrated and 22.5% had an impending dehydration according to serum osmolality. Multivariate analysis suggested that skin surface pH and epidermal hydration at the face were associated with fluid intake. Serum osmolality was associated with epidermal hydration at the leg and skin surface pH at the face. Fluid intake was not correlated with serum osmolality. Diuretics were associated with high serum osmolality. CONCLUSIONS: Approximately half of the patients were diagnosed as being dehydrated according to osmolality, which is the current reference standard. However, there was no association with fluid intake, questioning the clinical relevance of this measure. Results indicate that single skin barrier parameters are poor markers for fluid intake or osmolality. Epidermal hydration might play a role but most probably in combination with other tests.

Body mass index and lung cancer risk: a pooled analysis based on nested case-control studies from four cohort studies.

BACKGROUND: Obesity has been proposed as a potential protective factor against lung cancer. We examined the association between BMI and lung cancer risk in a pooled analysis based on nested case-control studies from four cohort studies. METHODS: A case-control study was nested within four cohorts in USA, Europe, China and Singapore that included 4172 cases and 8471 control subjects. BMI at baseline was calculated as weight in kilograms divided by height in meters squared (kg/m2), and classified into 4 categories: underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30) and obese (≥30). Odds ratios (ORs) and 95% confidence intervals (CIs) for BMI-lung cancer associations were estimated using unconditional logistic regression, adjusting for potential confounders. RESULTS: Considering all participants, and using normal weight as the reference group, a decreased risk of lung cancer was observed for those who were overweight (OR 0.77, 95% CI: 0.68-0.86) and obese (OR 0.69, 95% CI: 0.59-0.82). In the stratified analysis by smoking status, the decreased risk for lung cancer was observed among current, former and never smokers (P for interaction 0.002). The adjusted ORs for overweight and obese groups were 0.79 (95% CI: 0.68-0.92) and 0.75 (95% CI: 0.60-0.93) for current smokers, 0.70 (95% CI: 0.53-0.93) and 0.55 (95% CI: 0.37-0.80) for former smokers, 0.77 (95% CI: 0.59-0.99), and 0.71 (95% CI: 0.44-1.14) for never smokers, respectively. While no statistically significant association was observed for underweight subjects who were current smokers (OR 1.24, 95% CI: 0.98-1.58), former smokers (OR 0.27, 95% CI: 0.12-0.61) and never smokers (OR 0.83, 95% CI: 0.5.-1.28). CONCLUSION: The results of this study provide additional evidence that obesity is associated with a decreased risk of lung cancer. Further biological studies are needed to address this association.

Separate and combined associations of obesity and metabolic health with coronary heart disease: a pan-European case-cohort analysis.

Aims: The hypothesis of 'metabolically healthy obesity' implies that, in the absence of metabolic dysfunction, individuals with excess adiposity are not at greater cardiovascular risk. We tested this hypothesis in a large pan-European prospective study. Methods and results: We conducted a case-cohort analysis in the 520 000-person European Prospective Investigation into Cancer and Nutrition study ('EPIC-CVD'). During a median follow-up of 12.2 years, we recorded 7637 incident coronary heart disease (CHD) cases. Using cut-offs recommended by guidelines, we defined obesity and overweight using body mass index (BMI), and metabolic dysfunction ('unhealthy') as ≥ 3 of elevated blood pressure, hypertriglyceridaemia, low HDL-cholesterol, hyperglycaemia, and elevated waist circumference. We calculated hazard ratios (HRs) and 95% confidence intervals (95% CI) within each country using Prentice-weighted Cox proportional hazard regressions, accounting for age, sex, centre, education, smoking, diet, and physical activity. Compared with metabolically healthy normal weight people (reference), HRs were 2.15 (95% CI: 1.79; 2.57) for unhealthy normal weight, 2.33 (1.97; 2.76) for unhealthy overweight, and 2.54 (2.21; 2.92) for unhealthy obese people. Compared with the reference group, HRs were 1.26 (1.14; 1.40) and 1.28 (1.03; 1.58) for metabolically healthy overweight and obese people, respectively. These results were robust to various sensitivity analyses. Conclusion: Irrespective of BMI, metabolically unhealthy individuals had higher CHD risk than their healthy counterparts. Conversely, irrespective of metabolic health, overweight and obese people had higher CHD risk than lean people. These findings challenge the concept of 'metabolically healthy obesity', encouraging population-wide strategies to tackle obesity.

Nut intake and 5-year changes in body weight and obesity risk in adults: results from the EPIC-PANACEA study.

PURPOSE: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years. METHODS: This study includes 373,293 men and women, 25-70 years old, recruited between 1992 and 2000 from 10 European countries in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Habitual intake of nuts including peanuts, together defined as nut intake, was estimated from country-specific validated dietary questionnaires. Body weight was measured at recruitment and self-reported 5 years later. The association between nut intake and body weight change was estimated using multilevel mixed linear regression models with center/country as random effect and nut intake and relevant confounders as fixed effects. The relative risk (RR) of becoming overweight or obese after 5 years was investigated using multivariate Poisson regressions stratified according to baseline body mass index (BMI). RESULTS: On average, study participants gained 2.1 kg (SD 5.0 kg) over 5 years. Compared to non-consumers, subjects in the highest quartile of nut intake had less weight gain over 5 years (-0.07 kg; 95% CI -0.12 to -0.02) (P trend = 0.025) and had 5% lower risk of becoming overweight (RR 0.95; 95% CI 0.92-0.98) or obese (RR 0.95; 95% CI 0.90-0.99) (both P trend <0.008). CONCLUSIONS: Higher intake of nuts is associated with reduced weight gain and a lower risk of becoming overweight or obese.

Tall height and obesity are associated with an increased risk of aggressive prostate cancer: results from the EPIC cohort study.

BACKGROUND: The relationship between body size and prostate cancer risk, and in particular risk by tumour characteristics, is not clear because most studies have not differentiated between high-grade or advanced stage tumours, but rather have assessed risk with a combined category of aggressive disease. We investigated the association of height and adiposity with incidence of and death from prostate cancer in 141,896 men in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). After an average of 13.9 years of follow-up, there were 7024 incident prostate cancers and 934 prostate cancer deaths. RESULTS: Height was not associated with total prostate cancer risk. Subgroup analyses showed heterogeneity in the association with height by tumour grade (P heterogeneity = 0.002), with a positive association with risk for high-grade but not low-intermediate-grade disease (HR for high-grade disease tallest versus shortest fifth of height, 1.54; 95% CI, 1.18-2.03). Greater height was also associated with a higher risk for prostate cancer death (HR = 1.43, 1.14-1.80). Body mass index (BMI) was significantly inversely associated with total prostate cancer, but there was evidence of heterogeneity by tumour grade (P heterogeneity = 0.01; HR = 0.89, 0.79-0.99 for low-intermediate grade and HR = 1.32, 1.01-1.72 for high-grade prostate cancer) and stage (P heterogeneity = 0.01; HR = 0.86, 0.75-0.99 for localised stage and HR = 1.11, 0.92-1.33 for advanced stage). BMI was positively associated with prostate cancer death (HR = 1.35, 1.09-1.68). The results for waist circumference were generally similar to those for BMI, but the associations were slightly stronger for high-grade (HR = 1.43, 1.07-1.92) and fatal prostate cancer (HR = 1.55, 1.23-1.96). CONCLUSIONS: The findings from this large prospective study show that men who are taller and who have greater adiposity have an elevated risk of high-grade prostate cancer and prostate cancer death.