Spatial characteristics of non-communicable diseases and their associations to social conditions in a large urban cohort in Germany-Results from the Hamburg City Health Study.

BACKGROUND: Non-communicable diseases (NCDs) are responsible for many deaths. They are associated with several modifiable and metabolic risk factors and are therefore prone to significant regional variations on different scales. However, only few intra-urban studies examined spatial variation in NCDs and its association with social circumstances, especially in Germany. Thus, the present study aimed to identify associations of personal risk factors and local social conditions with NCDs in a large German city. METHODS: This study is based on a population-based cohort of the Hamburg City Health Study including 10,000 probands. Six NCDs were analyzed (chronic obstructive pulmonary disease [COPD], coronary heart disease [CHD], diabetes mellitus, heart failure, depression, and hypertension) in 68 city district clusters. As risk factors, we considered socio-demographic variables (age, sex, education) and risk behaviour variables (smoking, alcohol consumption). Logistic regression analyses identified associations between the district clusters and the prevalence rates for each NCD. Regional variation was detected by Gini coefficients and spatial cluster analyses. Local social condition indexes were correlated with prevalence rates of NCDs on city district level and hot-spot analyses were performed for significant high or low values. RESULTS: The analyses included 7,308 participants with a mean age of 63.1 years (51.5% female). The prevalence of hypertension (67.6%) was the highest. Risk factor associations were identified between smoking, alcohol consumption and education and the prevalence of NCDs (hypertension, diabetes, and COPD). Significant regional variations were detected and persisted after adjusting for personal risk factors. Correlations for prevalence rates with the local social conditions were significant for hypertension (r = 0.294, p < 0.02), diabetes (r = 0.259, p = 0.03), and COPD (r = 0.360, p < 0.01). CONCLUSIONS: The study shows that regional differences in NCD prevalence persist even after adjusting for personal risk factors. This highlights the central role of both personal socio-economic status and behaviors such as alcohol and tobacco consumption. It also highlights the importance of other potential regional factors (e.g. the environment) in shaping NCD prevalence. This knowledge helps policy- and decision-makers to develop intervention strategies.

Cross-Sectional Association of Dietary Patterns and Supplement Intake with Presence and Gray-Scale Median of Carotid Plaques-A Comparison between Women and Men in the Population-Based Hamburg City Health Study.

This population-based cross-sectional cohort study investigated the association of the Mediterranean and DASH (Dietary Approach to Stop Hypertension) diet as well as supplement intake with gray-scale median (GSM) and the presence of carotid plaques comparing women and men. Low GSM is associated with plaque vulnerability. Ten thousand participants of the Hamburg City Health Study aged 45-74 underwent carotid ultrasound examination. We analyzed plaque presence in all participants plus GSM in those having plaques (n = 2163). Dietary patterns and supplement intake were assessed via a food frequency questionnaire. Multiple linear and logistic regression models were used to assess associations between dietary patterns, supplement intake and GSM plus plaque presence. Linear regressions showed an association between higher GSM and folate intake only in men (+9.12, 95% CI (1.37, 16.86), p = 0.021). High compared to intermediate adherence to the DASH diet was associated with higher odds for carotid plaques (OR = 1.18, 95% CI (1.02, 1.36), p = 0.027, adjusted). Odds for plaque presence were higher for men, older age, low education, hypertension, hyperlipidemia and smoking. In this study, the intake of most supplements, as well as DASH or Mediterranean diet, was not significantly associated with GSM for women or men. Future research is needed to clarify the influence, especially of the folate intake and DASH diet, on the presence and vulnerability of plaques.

Performance of an interferon-γ release assay-based test for cell-mediated immunity to SARS-CoV-2.

In search for immunological correlates of protection against acute coronavirus disease 2019 (COVID-19) there is a need for high through-put assays for cell-mediated immunity (CMI) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We established an interferon-γ release assay -based test for detection of CMI against SARS-CoV-2 spike (S) or nucleocapsid (NC) peptides. Blood samples obtained from 549 healthy or convalescent individuals were measured for interferon-γ (IFN-γ) production after peptide stimulation using a certified chemiluminescence immunoassay. Test performance was calculated applying cutoff values with the highest Youden indices in receiver-operating-characteristics curve analysis and compared to a commercially available serologic test. Potential confounders and clinical correlates were assessed for all test systems. 522 samples obtained from 378 convalescent in median 298 days after PCR-confirmed SARS-CoV-2 infection and 144 healthy control individuals were included in the final analysis. CMI testing had a sensitivity and specificity of up to 89% and 74% for S peptides and 89% and 91% for NC peptides, respectively. High white blood cell counts correlated negatively with IFN-γ responses but there was no CMI decay in samples obtained up to one year after recovery. Severe clinical symptoms at time of acute infection were associated with higher measures of adaptive immunity and reported hair loss at time of examination. This laboratory-developed test for CMI to SARS-CoV-2 NC peptides exhibits excellent test performance, is suitable for high through-put routine diagnostics, and should be evaluated for clinical outcome prediction in prospective pathogen re-exposure.

[Non-utilisation of medical services during the COVID-19 pandemic among persons with chronic diseases]. / Nichtinanspruchnahme medizinischer Leistungen in der COVID-19-Pandemie bei Personen mit chronischen Erkrankungen.

INTRODUCTION: The COVID-19 pandemic is also impacting the medical care for other diseases. The extent to which people with chronic diseases are affected by the suspension of medical services is investigated-differentiating between patient and provider perspectives. METHOD: A cross-sectional study was conducted based on data from the longitudinal Hamburg City Health Study (HCHS). The study population was all HCHS participants (a sample of the population of Hamburg, 45-74 years) between April 2020 and November 2021. Utilisation of medical services was collected via the "COVID-19-module" of the HCHS. The chronic conditions included cardiovascular disease, kidney and lung disease, cancer and diabetes mellitus; analyses were descriptive and multivariate. RESULTS: Of the 2047 participants, 47.9% had at least one previous illness. Of those with pre-existing conditions, 21.4% had at least one healthcare service suspended or an appointment cancelled. In addition, 15.4% stated that they decided by themselves not to attend a doctor's appointment. Specialist care services (43.8% of all cancellations) were cancelled more frequently than general practitioner care (16.6%). After adjustment for age, gender and education, lung disease (OR 1.80; p < 0.008) and cancer (OR 2.33; p < 0.001) were found to be independent risk factors for appointment cancellations by healthcare providers. Of cancellations by patients, 42.2% were due to their fear of an infection with the coronavirus SARS-CoV­2. DISCUSSION: Health policy and the media are faced with the challenge of dealing with fears of infection in the population in such a way that they do not lead to an avoidance of necessary care services.

Detection of stage I HPV-driven oropharyngeal cancer in asymptomatic individuals in the Hamburg City Health Study using HPV16 E6 serology - A proof-of-concept study.

Background: The lack of detectable precancerous lesions poses challenges to the early detection of human papillomavirus-driven oropharyngeal cancer (HPV-OPC). Antibodies against HPV16 early proteins, especially E6, are uniquely sensitive and specific biomarkers detectable years prior to HPV-OPC diagnosis. Thus, HPV16 early protein serology warrants clinical investigation for HPV-OPC screening. Methods: Using multiplex serology, we analyzed HPV16 serum antibodies of the first 5000 participants (n=4,424 sera, recruited 2016-2017) of the Hamburg City Health Study, a population-based prospective cohort (45-74 years). Participants seropositive for HPV16 E6 and at least one additional early protein (E1, E2, E7) were considered at high risk for HPV-OPC development and invited to six-monthly non-invasive head and neck follow-up (FU) examinations (visual inspection, endoscopy, ultrasonography, performed 2019-2020). Participants with suspicious lesions were examined by magnetic resonance imaging and panendoscopy with biopsy. Histologically confirmed OPC cases were treated according to standard of care. Findings: In total, 35 out of 4,424 study participants (0·8%, 95% confidence interval (CI) 0·6-1·1%) were HPV16 E6 seropositive. Among these, eleven (0·3%, 95%CI 0·1-0·5%) were considered at high risk for HPV-OPC of which nine were successfully re-contacted and invited to regular clinical FU examinations. Two males and one female were diagnosed with stage I HPV-OPC within 1·3 years of clinical FU (3-4 years after initial blood draw), representing one diagnosis of prevalent advanced disease, one incident diagnosis of advanced disease, and one incident diagnosis of early disease. The remaining participants showed no detectable signs of cancer, and undergo regular examinations (median clinical FU: 1·0 years, median total FU from blood draw to last clinical FU visit: 4·7 years). Interpretation: HPV16 early antibodies allowed identifying three asymptomatic stage I HPV-OPC patients, out of eleven participants considered at high risk. However, two of the three cases already showed signs of advanced disease at diagnosis. Targeting multiple early proteins may considerably improve the positive predictive value of HPV16 serology and may have clinical utility for HPV-OPC screening. Funding: This work was funded by DKFZ and UKE intramural funding.

Alpha-Synuclein and Its Role in Melanocytes.

Pigmentation is an important process in skin physiology and skin diseases and presumably also plays a role in Parkinson's disease (PD). In PD, alpha-Synuclein (aSyn) has been shown to be involved in the pigmentation of neurons. The presynaptic protein is intensively investigated for its pathological role in PD, but its physiological function remains unknown. We hypothesized that aSyn is both involved in melanocytic differentiation and melanosome trafficking processes. We detected a strong expression of aSyn in human epidermal melanocytes (NHEMs) and observed its regulation in melanocytic differentiation via the microphthalmia-associated transcription factor (MITF), a central regulator of differentiation. Moreover, we investigated its role in pigmentation by performing siRNA experiments but found no effect on the total melanin content. We discovered a localization of aSyn to melanosomes, and further analysis of aSyn knockdown revealed an important role in melanocytic morphology and a reduction in melanosome release. Additionally, we found a reduction of transferred melanosomes in co-culture experiments of melanocytes and keratinocytes but no complete inhibition of melanosome transmission. In summary, this study highlights a novel physiological role of aSyn in melanocytic morphology and its so far unknown function in the pigment secretion in melanocytes.

Role of Amino Acid Transporter SNAT1/SLC38A1 in Human Melanoma.

The tumor metabolism is an important driver of cancer cell survival and growth, as rapidly dividing tumor cells exhibit a high demand for energetic sources and must adapt to microenvironmental changes. Therefore, metabolic reprogramming of cancer cells and the associated deregulation of nutrient transporters are a hallmark of cancer cells. Amino acids are essential for cancer cells to synthesize the necessary amount of protein, DNA, and RNA. Although cancer cells can synthesize glutamine de novo, most cancer cells show an increased uptake of glutamine from the tumor microenvironment. Especially SNAT1/SLC38A1, a member of the sodium neutral amino acid transporter (SNAT) family, plays an essential role during major net import of glutamine. In this study, we revealed a significant upregulation of SNAT1 expression in human melanoma tissue in comparison to healthy epidermis and an increased SNAT1 expression level in human melanoma cell lines when compared to normal human melanocytes (NHEMs). We demonstrated that functional inhibition of SNAT1 with α-(methylamino) isobutyric acid (MeAIB), as well as siRNA-mediated downregulation reduces cancer cell growth, cellular migration, invasion, and leads to induction of senescence in melanoma cells. Consequently, these results demonstrate that the amino acid transporter SNAT1 is essential for cancer growth, and indicates a potential target for cancer chemotherapy.

Epidemiology of skin diseases in Germany: systematic review of the current state of research - part 2: non-infectious skin diseases.

The aim of this work was to systematically collect all previously published population-based epidemiological data on skin diseases in Germany. The present part 2 of the publication series deals with non-infectious skin diseases. The results on cutaneous tumor diseases (part 1) and infectious skin diseases (part 3) form the other parts of this publication series. A systematic literature search was performed using PubMed/MEDLINE for the period of the last 15 years. With the aim of including all dermatologic diseases, a diagnostic list was developed based on the ICD-11 catalogue. This list included 1,347 skin diseases and formed the basis for the search. The literature search yielded 4,650 hits, of which 72 were included in the synthesis. Among them were 37 publications on non-infectious skin diseases. Among these, psoriasis and atopic eczema were the most common. The highest lifetime prevalence was found for acne. This work is the first systematic literature review that aimed to report all available epidemiological data on skin diseases in Germany. It was found that representative data on many non-infectious diseases are not yet available. Among the included studies, there was a high heterogeneity regarding the methodology. Nevertheless, the utility of these epidemiological data is wide-ranging and can serve as a reference of various epidemiological questions.

Epidemiology of skin diseases in Germany: systematic review of the current state of research - part 3: infectious skin diseases.

The aim of this work was to systematically collect all previously published population-based epidemiological data on skin diseases in Germany. A systematic literature search was performed using PubMed/MEDLINE for the period of the last 15 years. With the aim to include all dermatological diseases, a diagnostic list based on the ICD-11 catalogue was compiled. This list included 1,347 skin diseases and formed the basis for the search. The present part 3 of the publication series deals with infectious skin diseases. The results on cutaneous tumor diseases (part 1) and non-infectious skin diseases (part 2) form the other parts of this publication series. The literature search yielded 4,605 hits, of which 72 papers on 43 different skin diseases were included in the synthesis. Among them were twelve hits on infectious dermatoses, of which six papers were related to measles. The highest lifetime prevalence rates were found for varicella and verrucae vulgaris. This work is the first systematic literature review that aimed to report all available epidemiological data on skin diseases in Germany. It was found that representative data on many infectious diseases are not yet available. Among the included studies, a high heterogeneity was found with regard to the methodology. Nevertheless, these epidemiological data have a wide range of uses and can serve as a reference for various epidemiological questions.

Epidemiology of skin diseases in Germany: systematic review of the current state of research - part 1: cutaneous tumor diseases.

Epidemiological data are of great importance for the identification of health care needs, the detection of gaps in care, the development of targeted prevention measures, and for the optimization of resource allocation. The aim of this work was to systematically collect all previously published population-based epidemiological data on skin diseases in Germany. The present part 1 of the publication series deals with tumor diseases of the skin. The results on non-infectious (part 2) and infectious skin diseases (part 3) form the other parts of this publication series. A systematic search of the literature spanning the last 15 years was conducted using the PubMed/MEDLINE database. With the aim of including all dermatologic diseases, a diagnostic list was developed based on the ICD-11 catalogue. This list included 1,347 skin diseases and formed the basis for the search. The literature search yielded 4,650 publications. After two-stage screening, 72 studies on 43 different skin diseases were included in the synthesis. Among them were 30 publications on cutaneous tumor diseases, the majority was related to malignant melanoma. This work is the first systematic literature review that aimed to report all available epidemiological data on skin diseases in Germany. In terms of study characteristics, a high heterogeneity was found for the different skin diseases. Even though the methodology of the included epidemiological studies varied considerably, the usefulness of these epidemiological data is extremely wide-ranging. Thus, this work can serve as a reference for various epidemiological questions.

Multi-organ assessment in mainly non-hospitalized individuals after SARS-CoV-2 infection: The Hamburg City Health Study COVID programme.

AIMS: Long-term sequelae may occur after SARS-CoV-2 infection. We comprehensively assessed organ-specific functions in individuals after mild to moderate SARS-CoV-2 infection compared with controls from the general population. METHODS AND RESULTS: Four hundred and forty-three mainly non-hospitalized individuals were examined in median 9.6 months after the first positive SARS-CoV-2 test and matched for age, sex, and education with 1328 controls from a population-based German cohort. We assessed pulmonary, cardiac, vascular, renal, and neurological status, as well as patient-related outcomes. Bodyplethysmography documented mildly lower total lung volume (regression coefficient -3.24, adjusted P = 0.014) and higher specific airway resistance (regression coefficient 8.11, adjusted P = 0.001) after SARS-CoV-2 infection. Cardiac assessment revealed slightly lower measures of left (regression coefficient for left ventricular ejection fraction on transthoracic echocardiography -0.93, adjusted P = 0.015) and right ventricular function and higher concentrations of cardiac biomarkers (factor 1.14 for high-sensitivity troponin, 1.41 for N-terminal pro-B-type natriuretic peptide, adjusted P ≤ 0.01) in post-SARS-CoV-2 patients compared with matched controls, but no significant differences in cardiac magnetic resonance imaging findings. Sonographically non-compressible femoral veins, suggesting deep vein thrombosis, were substantially more frequent after SARS-CoV-2 infection (odds ratio 2.68, adjusted P < 0.001). Glomerular filtration rate (regression coefficient -2.35, adjusted P = 0.019) was lower in post-SARS-CoV-2 cases. Relative brain volume, prevalence of cerebral microbleeds, and infarct residuals were similar, while the mean cortical thickness was higher in post-SARS-CoV-2 cases. Cognitive function was not impaired. Similarly, patient-related outcomes did not differ. CONCLUSION: Subjects who apparently recovered from mild to moderate SARS-CoV-2 infection show signs of subclinical multi-organ affection related to pulmonary, cardiac, thrombotic, and renal function without signs of structural brain damage, neurocognitive, or quality-of-life impairment. Respective screening may guide further patient management.

Estimating prevalence and incidence of skin cancer in Germany.

BACKGROUND AND OBJECTIVES: The aim of the present study was to determine the prevalence and incidence of skin cancer. PATIENTS AND METHODS: We calculated prevalence and incidence for cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) in 2012 in Germany, using claims data of 2.1 million insured persons. In order to allow statements concerning differences between subgroups, we calculated 95 % confidence intervals. Finally, we standardized prevalence and incidence with regard to the German population. RESULTS: The prevalence and incidence of CM amounted to 0.12 % and 0.04 % and increased with age. For NMSC these measures were 0.65 % and 0.15 %. Of the prevalent and incident patients, 88.9 % and 87.4 % (CM) and 99.4 % and 98.8 % (NMSC) respectively were at early stages. A projection on the whole population resulted in 75,419 persons affected by CM and 376,004 persons affected by NMSC, including 24,075 (CM) and 84,618 (NMSC) incident patients. CONCLUSIONS: In this study, we defined epidemiological measures according to the number of patients affected by skin cancer and having a medical consultation indicating a need for treatment. These results can serve in future research as a data basis for analysis of health service demand in skin cancer patients and the associated costs.

[Psycho-oncology in dermatological practice : Evaluation of need and care structures]. / Psychoonkologie in dermatologischen Praxen : Bedarfseinschätzung und Versorgungsstrukturen.

BACKGROUND: Psycho-oncological care is a main component of comprehensive oncological care as stated in the National Cancer Plan of the German Federal Government. Correspondingly this goal has been adopted in the strategy of the German Skin Cancer Council. In certified skin cancer centers structural requirements for psycho-oncological care are established. Nevertheless, a large proportion of skin cancer patients are treated in dermatological practices. Up to now data on psycho-oncological care in dermatological practices are missing. MATERIALS UND METHODS: We conducted a descriptive cross-sectional written survey on psycho-oncological care in dermatological practices from October 2016 to February 2017. RESULTS: In all, 171 practices completed the questionnaire; 19.4% of these practices have an oncological focus. The mean number of treated skin cancer patients was 554.3 ± 659.1 and 62.4 ± 73.6 for melanoma patients. Dermatologists estimated a low proportion (≤5%) of patients with need for psycho-oncological care; however, 21.9% of practices actively offer information on psycho-oncological programs and 26.1% cooperate with psycho-oncological care providers. Interest in psycho-oncological care concepts was stated by 29.3%. CONCLUSIONS: Psycho-oncological care is only occasionally and partly deficiently provided in dermatological practices including referral to psycho-oncological care professionals. The results emphasize the necessity to raise awareness regarding psycho-oncological needs of skin cancer patients and to integrate psycho-oncological counselling into clinical routine in dermatological practices.

What is psoriasis? - Perception and assessment of psoriasis among the German population.

BACKGROUND: Delivery of health care to psoriasis patients plays an important role in the field of dermatology. Following the 2014 WHO resolution and the 2016 WHO global report, there has been an increase in the awareness of psoriasis among the general public. However, the perception of psoriasis by the general population remains unclear. The goal of the present study was to investigate the perception and assessment of psoriasis among the German population. PATIENTS AND METHODS: Representative telephone survey among 2,001 adults using a standardized questionnaire. Analyses with respect to place of residence, age, gender and level of education were conducted in a descriptive manner. RESULTS: Twenty-nine percent of participants were familiar with the term "Psoriasis"; 86 %, with the German designation "Schuppenflechte". Ninety-three percent considered the disease to be a significant burden for affected individuals; 59 % stated that there were effective drugs available for psoriasis; 9 % considered the disease to be communicable. Ten percent reported that they would not want to live in the same household as an affected individual; 23 % did not want to share the same swimming pool; and 27 % did not want to be in a personal relationship with someone affected. Twelve percent stated to be familiar with the WHO resolution on psoriasis; 6 % with the World Psoriasis Day; and 3 % with the "Bitte berühren" ("Please touch") campaign. CONCLUSIONS: Although a majority of the German population is familiar with the term "Schuppenflechte", there is a significant lack of knowledge about the disease as well as prejudice toward affected individuals. Further measures are required to improve the level of information and decrease stigmatization.

Was ist Schuppenflechte? - Wahrnehmung und Bewertung der Psoriasis in der deutschen Bevölkerung.

HINTERGRUND: Die Versorgung der Psoriasis vulgaris nimmt in der Dermatologie einen wichtigen Stellenwert ein. Im Zuge der WHO-Resolution 2014 und des WHO Global Reports 2016 hat die öffentliche Aufmerksamkeit für die Psoriasis zugenommen. Unklar ist, wie Psoriasis in der Allgemeinbevölkerung wahrgenommen wird. Ziel ist die Erfassung der Wahrnehmung und Bewertung von Psoriasis in der Bevölkerung. PATIENTEN UND METHODEN: Repräsentative Telefonumfrage mit 2001 Erwachsenen mittels eines standardisierten Fragebogens. Die Auswertungen erfolgten deskriptiv nach Region, Alter, Geschlecht und Bildungsstatus. ERGEBNISSE: Die Begriffe Psoriasis bzw. Schuppenflechte waren 29 % bzw. 86 % der Befragten, bekannt. 93 % schätzten die Krankheit als sehr belastend für die Betroffenen ein, 59 % nahmen an, dass es wirksame Medikamente gegen Schuppenflechte gibt und 9 % hielten diese Erkrankung für ansteckend. 10 % würden nicht mit einer betroffenen Person im Haushalt leben wollen, 23 % nicht mit Betroffenen ins Schwimmbad gehen und 27 % nicht in einer Partnerschaft sein. 12 % gaben an, die WHO-Resolution zur Psoriasis zu kennen, 6 % den Weltpsoriasistag und 3 % die Kampagne "Bitte berühren". SCHLUSSFOLGERUNGEN: Wenngleich einer Mehrheit in der deutschen Bevölkerung die Schuppenflechte bekannt ist, bestehen deutliche Wissensdefizite und teilweise Vorurteile gegenüber dieser Erkrankung. Weitergehende Maßnahmen zur besseren Information und zur Minderung der Stigmatisierung sind notwendig.