Cardiovascular disease in Switzerland - health care, mortality and geographical pattern

SUMMARY Switzerland is facing an aging population and a growing amount of patients with chronic diseases. It is crucial to display health care processes and pathways, to identify inequalities and obstacles, and to point out possibilities for improvements of the Swiss health care system (e.g. increase efficiency). The introductory part of the thesis presents a brief description of the Swiss health care system, health services research and regional variation as well as an introduction of CVD and its epidemiological key figures, aetiology and treatments. This is followed by the description of the utilized methods and data, and the objectives of this thesis. The subsequent sections present the four articles included in this thesis. The first article focuses on a small area analysis on regional variation of avoidable hospitalisations in Switzerland including density of primary care physicians and specialists, rurality and hospital supply factors as explanatory variables in the analysis. Lower rates of avoidable hospitalisations were found in areas with very high supply of primary care physicians, increased avoidable hospitalisation rates in areas with more specialists and in areas with higher proportion of rural residents. The second article aims to examine whether emergency patients with acute ST-segment elevation myocardial infarction were adequately treated, i.e. according to the treatment guidelines, in Switzerland. Results show that older and female patients were less likely to receive revascularization which suggests that the treatment guidelines may not be uniformly applied in Switzerland. Similar to the first article, also in the third article a small area analysis was performed but this time investigating regional variation in costs at the end of life. Strongest associations of cost was found with cause of death, age and language region of the decedents. The strong spatial variation of costs could only partly be explained by the included covariates. Article four aims to examine the relationship of distance to different hospital types and mortality from AMI or stroke. We found that AMI mortality in the Swiss population 30 and older and stroke mortality in those 65 and above increased with distance to central and university hospitals, while adjusting for sociodemographic and economic characteristics of the population. The presentation of the four articles is followed by a discussion, which summarizes the main findings and the strengths and limitations of the presented articles. The thesis concludes with a discussion about the challenges for policy, practice and future research

Kartierung des HLA-Ligandoms der akuten myeloischen Leukämie zur Entwicklung einer therapeutischen Multipeptidvakzine

Zusammenfassung: Bahnbrechende Entwicklungen im Bereich der Immuntherapie (u.a. Checkpoint- Inhibitoren, CAR-T-Zellen) haben das (klinische) Potential einer T-Zell-basierten Therapie für eine effektive Malignombehandlung deutlich herausgestellt. Vor dem Hintergrund mäßiger 5-Jahresüberlebensraten im Rahmen der aktuellen Therapieoptionen, der erwiesenen Immunogenität dieser Erkrankung (u.a. im Rahmen der HSCT in Form des Graft-vs-Leukemia-Effekts), sowie des quantitativ günstigen Verhältnisses von Immuneffektor- zu Zielzellen nach Erreichen einer klinischen Remission erscheint eine Peptidvakzinierung ein attraktiver alternativer Behandlungsansatz für dieses Krankheitsbild. Auf der Grundlage genomischer Analysen und reverser Immunologie wurden bisher einige wenige AML-assoziierte Peptide beschrieben, deren klinische Effektivität jedoch bis dato nicht eindeutig gezeigt werden konnte. Für die Identifikation physiologisch relevanter Vakzinkandidaten wurde im Rahmen dieser Arbeit erstmals ein direkter Massenspektrometrie-basierter Analyseansatz des natürlich präsentierten HLA-Ligandoms gewählt. Die Kartierung des HLA-Klasse-I- Ligandomes von 15 AML Patienten und 35 gesunden Spendern ergab mehr als 25 000 verschiedene, natürlich präsentierte HLA-Peptide. Die Priorisierung der potentiellen Kandidaten erfolgte v.a. auf der Basis der AML-Exklusivität und einer hohen Präsentationsfrequenz in der AML-Kohorte. Eine Präsentation dieser Peptide konnte Subgruppen-übergreifend in mehr als 20 % der einzelnen AML-Patientenligandome nachgewiesen werden. Darüberhinaus konnten auch einige natürlich präsentierte HLA-Liganden bereits etablierter AML-assoziierter Antigene identifiziert werden. 80 % dieser Antigene wurden jedoch auch im HLA-Ligandom gesunder Spender detektiert. Im Zuge der HLA-Klasse-II-Ligandom-Kartierung von 12 AML-Patienten und 13 PBMC-Spendern wurden über 1000 verschiedene Quellproteine identifiziert. Ein Vergleich des HLA-exklusiven Quellproteoms beider Klassen ergab 43 gemeinsame Proteine, sowie drei HLA-Klasse-I-Liganden, deren Sequenz vollständig in ihren Klasse-II-Pendants enthalten war. Eine grob-orientierend durchgeführte, funktionelle Charakterisierung ausgewählter Peptidkandikaten beider HLA-Klassen lieferte erste Hinweise auf eine AML- spezifische Immunogenität einiger im Rahmen dieser Arbeit definierter Antigene

The Swiss neighbourhood index of socioeconomic position: update and re-validation.

BACKGROUND The widely used Swiss neighbourhood index of socioeconomic position (Swiss-SEP 1) was based on data from the 2000 national census on rent, household head education and occupation, and crowding. It may now be out of date. METHODS We created a new index (Swiss-SEP 2) based on the 2012-2015 yearly micro censuses that have replaced the decennial house-to-house census in Switzerland since 2010. We used principal component analysis on neighbourhood-aggregated variables and standardised the index. We also created a hybrid version (Swiss-SEP 3), with updated values for neighbourhoods centred on buildings constructed after the year 2000 and original values for the remaining neighbourhoods. RESULTS A total of 1.54 million neighbourhoods were included. With all three indices, the mean yearly equivalised household income increased from around 52,000 to 90,000 CHF from the lowest to the highest index decile. Analyses of mortality were based on 33.6 million person-years of follow-up. The age- and sex-adjusted hazard ratios of all-cause mortality comparing areas in the lowest Swiss-SEP decile with areas of the highest decile were 1.39 (95% confidence interval [CI] 1.36-1.41), 1.31 (1.29-1.33) and 1.34 (1.32-1.37) using the old, new and hybrid indices, respectively. DISCUSSION The Swiss-SEP indices capture area-based SEP at a high resolution and allow the study of SEP when individual-level SEP data are missing or area-level effects are of interest. The hybrid version (Swiss-SEP 3) maintains high spatial resolution while adding information on new neighbourhoods. The index will continue to be useful for Switzerland's epidemiological and public health research

Public preferences towards data management and governance in Swiss biobanks: results from a nationwide survey.

OBJECTIVES This article aims to measure the willingness of the Swiss public to participate in personalised health research, and their preferences regarding data management and governance. SETTING Results are presented from a nationwide survey of members of the Swiss public. PARTICIPANTS 15 106 randomly selected Swiss residents received the survey in September 2019. The response rate was 34.1% (n=5156). Respondent age ranged from 18 to 79 years, with fairly uniform spread across sex and age categories between 25 and 64 years. PRIMARY AND SECONDARY OUTCOME MEASURES Willingness to participate in personalised health research and opinions regarding data management and governance. RESULTS Most respondents preferred to be contacted and reconsented for each new project using their data (39%, 95% CI: 37.4% to 40.7%), or stated that their preference depends on the project type (29.4%, 95% CI: 27.9% to 31%). Additionally, a majority (52%, 95% CI: 50.3% to 53.8%) preferred their data or samples be stored anonymously or in coded form (43.4%, 95% CI: 41.7% to 45.1%). Of those who preferred that their data be anonymised, most also indicated a wish to be recontacted for each new project (36.8%, 95% CI: 34.5% to 39.2%); however, these preferences are in conflict. Most respondents desired to personally own their data. Finally, most Swiss respondents trust their doctors, along with researchers at universities, to protect their data. CONCLUSION Insight into public preference can enable Swiss biobanks and research institutions to create management and governance strategies that match the expectations and preferences of potential participants. Models allowing participants to choose how to interact with the process, while more complex, may increase individual willingness to provide data to biobanks

Sociodemographic and regional differences in neonatal and infant mortality in Switzerland: The Swiss National Cohort

SummaryBackgroundDespite a well-funded healthcare system with universal insurance coverage, Switzerland has one of the highest neonatal and infant mortality rates among high-income countries. Identifying avoidable risk factors targeted by evidence-based policies is a public health priority. We describe neonatal and infant mortality in Switzerland from 2011–2018 and explore associations with neonatal and pregnancy-related variables, parental sociodemographic information, regional factors, and socioeconomic position (SEP) using data from a long-term nation-wide cohort study.MethodsWe included 680,077 live births—representing 99.3% of all infants born in Switzerland between January 2011 and December 2018. We deterministically linked the national live birth register with the mortality register and with census and survey data to create a longitudinal dataset of neonatal and pregnancy-related variables; parental sociodemographic information, such as civil status, age, religion, education, nationality; regional factors, such as urbanity, language region; and the Swiss neighbourhood index of SEP (Swiss-SEP index). Information on maternal education was available for a random subset of 242,949 infants. We investigated associations with neonatal and infant mortality by fitting multivariable Poisson regression models with robust standard errors. Several sensitivity analyses assessed the robustness of our findings.ResultsOverall, neonatal mortality rates between 2011 and 2018 were 3.0 per 1000 live births, varying regionally from 3.2 in German-speaking to 2.4 in French-speaking and 2.1 in Italian-speaking Switzerland. For infant mortality, respective rates were 3.7 per 1000 live births overall, varying from 3.9 to 3.3 and 2.9. Adjusting for sex, maternal age, multiple birth and birth rank, neonatal mortality remained significantly associated with language region [rate ratio (RR) 0.72, 95% confidence interval (CI): 0.64–0.80 for French-speaking and RR 0.66, 95% CI: 0.51–0.87 for Italian-speaking region], with marital status (RR 1.55, 95% CI: 1.40–1.71 for unmarried), nationality (RR 1.40, 95% CI: 1.21–1.62 for non-European Economic Area vs. Swiss), and the Swiss-SEP index (RR 1.17, 95% CI: 1.00–1.36 for lowest vs. highest SEP quintile). In the subset, we showed a possible association of neonatal mortality with maternal education (RR 1.24, 95% CI: 0.95–1.61 for compulsory vs tertiary education).ConclusionWe provide detailed evidence about the social patterning of neonatal and infant mortality in Switzerland and reveal important regional differences with about 30% lower risks in French-and Italian-speaking compared with German-speaking regions. Underlying causes for such regional differences, such as cultural, lifestyle, or healthcare-related factors, warrant further exploration to inform and provide an evidence base for public health policies

A prospective cohort analysis of residential radon and UV exposures and malignant melanoma mortality in the Swiss population.

BACKGROUND Radon is a radioactive noble gas naturally found in the earth crust that can accumulate in buildings. In addition to lung cancer, alpha particles emitted by radon may contribute to the risk of skin cancer. We evaluated the association between residential radon exposure and skin cancer mortality, over a fifteen year period, taking residential ultra-violet (UV) exposure into account. METHODS We included 4.9 million adults from the Swiss National Cohort. Hazard ratios for melanoma mortality were estimated using Cox proportional hazard models (20+ years old; follow-up 2001-2015). Long-term modelled residential radon and ambient UV exposures were assigned at baseline, and included together in the Cox models. With age as a time scale, models were adjusted for calendar time, sex, marital status, education, mother tongue, socioeconomic position, and occupational environment with potential for UV exposure. Age specific hazard ratios were derived. Effect modification, sensitivity analyses and the shape of the exposure response, as well as secondary analysis using other outcome definitions, were investigated. RESULTS During follow-up (average of 13.6 years), 3,979 melanoma deaths were observed. Associations declined with age, with an adjusted hazard ratio per 100 Bq/m3 radon at age 60 of 1.10 (95% CI: 0.99, 1.23). The dose-response showed an approximate linear trend between the minimum and mean radon exposure of 75 Bq/m3. Having outdoor occupation significantly increased the risk of melanoma mortality associated with UV exposure compared to indoor jobs. Analysis restricted to the last five years of follow-up showed similar results compared to the main analysis. Similar associations were found for mortality from melanoma and non-melanoma skin cancer combined. CONCLUSION With double the follow-up time, this study confirmed the previously observed association between residential radon exposure and melanoma and non-melanoma skin cancer mortality in Switzerland. Accumulation of radon indoors is preventable and of public health importance

Trends in the use of mammography for early breast cancer detection in Switzerland: Swiss Health Surveys 2007 and 2012.

AIMS Breast cancer is the most common cancer in women worldwide. We assessed changes in the use of breast cancer screening 2007-2012 in Switzerland, and associations with socioeconomic and health-related determinants. METHODS We used the nationwide and representative data from the Swiss Health Surveys 2007 and 2012. We analysed the self-reported use of mammography in the last 12 months (proportion of population) among women aged 40-79 years, and opportunistic (without clinical symptoms, initiated by the woman or a physician) and programmatic screening mammography (as part of a systematic screening programme). We performed multivariate logistic regression analyses (presented as adjusted odds ratios, aORs). RESULTS The use of any mammography in the last 12 months declined from 19.1% (95% confidence interval [CI] 17.7-20.5%) in 2007 to 11.7% (95% CI 10.7-12.6%) in 2012. This decline was more pronounced in regions with a long-standing or no cantonal breast cancer screening programme (aOR 0.5, 95% CI 0.4-0.6, and aOR 0.5, 95% CI 0.4-0.6, respectively), but remained relatively stable in regions with a recently introduced programme (aOR 0.9, 95% CI 0.6-1.3, p-value from test for interaction 0.01). Opportunistic screening dropped from 12.0% (95% CI 10.9-13.2%) in 2007 to 6.2% (95% CI 5.5-6.9%; p <0.001) in 2012, whereas the use of programmatic mammography remained stable at 3.1% (95% CI 2.6-3.7%). Use of any mammography was higher in women aged 50-69 years, residing in a region with a systematic screening programme in place, and women having a private hospital stay insurance, but was not associated with education level and non-Swiss citizenship. CONCLUSIONS Overall attendance of breast cancer screening is low in Switzerland and decreased between 2007 and 2012, despite expanding cantonal mammography screening programmes. Many factors may have contributed to this decline, including the ongoing scientific and public debates on the value of breast cancer screening

Increasing trends in in situ breast cancer incidence in a region with no population-based mammographic screening program: results from Zurich, Switzerland 2003-2014

PURPOSE Increase in in situ breast cancer (BCIS) incidence has been reported across Europe and the USA. However, little is known about the trends in BCIS incidence in regions without population-based mammographic screening programs. We set out to investigate these trends in Zurich, Switzerland, where only opportunistic mammographic screening exists. METHODS Data from 989 women diagnosed with a primary BCIS between 2003 and 2014 were used in our analyses. Age-standardized incidence rates per 100,000 person-years (ASR) were computed per year. Additional analyses by BCIS subtype, by age group at diagnosis and by incidence period were conducted. Incidence trends over time were assessed using joinpoint regression analysis. RESULTS The overall BCIS ASR was 10.7 cases per 100,000 person-years with an increasing trend over the study period. A similar trend was observed for the ductal carcinoma in situ (DCIS) ASR, while the lobular carcinoma in situ (LCIS) ASR decreased. Age-specific analyses revealed that the 50-59 year age group had the highest BCIS ASR. The highest increase in BCIS ASR, even though not statistically significant, was observed for the < 40 year age group. CONCLUSIONS BCIS ASR increased linearly over a 12-year period. The increase was reflected by an increase in DCIS ASR, whereas LCIS ASR decreased over time. The highest increase in BCIS ASR over the study period was observed for the < 40 year age group, even though not statistically significant. Patient and tumor characteristics of this group that may be associated with BCIS development warrant further investigation

No significant gender difference in hospitalizations for acute coronary syndrome in Switzerland over the time period of 2001 to 2010.

BACKGROUND Morbidity and mortality from cardiovascular diseases have decreased since the 1970s in most Western societies. However, it is unclear if this positive trend can also be found in younger women suffering from acute coronary syndrome (ACS). METHODS This is a prospective single center registry study including 11.015 women and men hospitalized for a first ACS between the years 2001 and 2010. We analyzed ACS rates according to sex and age group using Poisson regression in order to assess temporal trends. RESULTS Overall ACS hospitalization rates per 100.000 inhabitants increased by 31% between 2001 and 2010 (Rate Ratio (RR) of 1.31, 95% CI 1.20-1.43; p<0.001) with a similar increase in men (RR 1.29, p<0.00001) and women (RR 1.35, p<0.0001). Analyses of age-specific ACS rates showed a significant increase in ACS hospitalization rates only for the age groups 70-79years (p=0.003) and 80+ years (p<0.00001). None of the age matched subgroups showed a sex related significant difference in trend for ACS hospitalization rates. Temporal trends for recorded risk factors showed a significant increase in smoking (p=0.03), and a trend to increased obesity prevalence (p=0.06) in females in the age group 60-69years. CONCLUSIONS In contrast to other studies, we found no evidence for a particular increase in the number of younger women referred for a first ACS during the years 2001 and 2010. Potential negative effects of smoking and obesity on ACS incidence may be delayed to women older than 70years

Death at no cost? Persons with no health insurance claims in the last year of life in Switzerland.

BACKGROUND Lack of health insurance claims (HIC) in the last year of life might indicate suboptimal end-of-life care, but reasons for no HIC are not fully understood because information on causes of death is often missing. We investigated association of no HIC with characteristics of individuals and their place of residence. METHODS We analysed HIC of persons who died between 2008 and 2010, which were obtained from six providers of mandatory Swiss health insurance. We probabilistically linked these persons to death certificates to get cause of death information and analysed data using sex-stratified, multivariable logistic regression. Supplementary analyses looked at selected subgroups of persons according to the primary cause of death. RESULTS The study population included 113,277 persons (46% males). Among these persons, 1199 (proportion 0.022, 95% CI: 0.021-0.024) males and 803 (0.013, 95% CI: 0.012-0.014) females had no HIC during the last year of life. We found sociodemographic and health differentials in the lack of HIC at the last year of life among these 2002 persons. The likelihood of having no HIC decreased steeply with older age. Those who died of cancer were more likely to have HIC (adjusted odds ratio for males 0.17, 95% CI: 0.13-0.22; females 0.19, 95% CI: 0.12-0.28) whereas those dying of mental and behavioural disorders (AOR males 1.83, 95% CI:1.42-2.37; females 1.65, 95% CI: 1.27-2.14), and males dying of suicide (AOR 2.15, 95% CI: 1.72-2.69) and accidents (AOR 2.41, 95% CI: 1.96-2.97) were more likely to have none. Single, widowed, and divorced persons also were more likely to have no HIC (AORs in range of 1.29-1.80). There was little or no association between the lack of HIC and characteristics of region of residence. Patterns of no HIC differed across main causes of death. Associations with age and civil status differed in particular for persons who died of cancer, suicide, accidents and assaults, and mental and behavioural disorders. CONCLUSIONS Particular groups might be more likely to not seek care or not report health insurance costs to insurers. Researchers should be aware of this aspect of health insurance data and account for persons who lack HIC