Hierarchical contribution of individual lifestyle factors and their interactions on adenomatous and serrated polyp risk.

BACKGROUND: Individual colorectal polyp risk factors are well characterized; however, insights into their pathway-specific interactions are scarce. We aimed to identify the impact of individual risk factors and their joint effects on adenomatous (AP) and serrated polyp (SP) risk. METHODS: We collected information on 363 lifestyle and metabolic parameters from 1597 colonoscopy participants, resulting in over 521,000 data points. We used multivariate statistics and machine-learning approaches to assess associations of single variables and their interactions with AP and SP risk. RESULTS: Individual factors and their interactions showed common and polyp subtype-specific effects. Abdominal obesity, high body mass index (BMI), metabolic syndrome, and red meat consumption globally increased polyp risk. Age, gender, and western diet associated with AP risk, while smoking was associated with SP risk. CRC family history was associated with advanced adenomas and diabetes with sessile serrated lesions. Regarding lifestyle factor interactions, no lifestyle or dietary adjustments mitigated the adverse smoking effect on SP risk, whereas its negative effect was exacerbated by alcohol in the conventional pathway. The adverse effect of red meat on SP risk was not ameliorated by any factor, but was further exacerbated by western diet along the conventional pathway. No modification of any factor reduced the negative impact of metabolic syndrome on AP risk, whereas increased fatless fish or meat substitutes' intake mitigated its effect on SP risk. CONCLUSIONS: Individual risk factors and their interactions for polyp formation along the adenomatous and serrated pathways are strongly heterogeneous. Our findings may facilitate tailored lifestyle recommendations and contribute to a better understanding of how risk factor combinations impact colorectal carcinogenesis.

Ticagrelor Monotherapy or Dual Antiplatelet Therapy After Drug-Eluting Stent Implantation: Per-Protocol Analysis of the GLOBAL LEADERS Trial.

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention-to-treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention-to-treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per-protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time-varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all-cause mortality or nonfatal Q-wave myocardial infarction at 2 years. At 2-year follow-up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per-protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75-1.03; P=0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79-1.26; P=0.99). The per-protocol and intention-to-treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1-year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01813435.

Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis.

Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis.

Healthcare trajectories and costs in the last year of life: a retrospective primary care and hospital analysis.

OBJECTIVES: To analyse healthcare utilisation and costs in the last year of life in England, and to study variation by cause of death, region of patient residence and socioeconomic status. METHODS: This is a retrospective cohort study. Individuals aged 60 years and over (N=108 510) who died in England between 2010 and 2017 were included in the study. RESULTS: Healthcare utilisation and costs in the last year of life increased with proximity to death, particularly in the last month of life. The mean total costs were higher among males (£8089) compared with females (£6898) and declined with age at death (£9164 at age 60-69 to £5228 at age 90+) with inpatient care accounting for over 60% of total costs. Costs decline with age at death (0.92, 95% CI 0.88 to 0.95, p<0.0001 for age group 90+ compared with to the reference category age group 60-69) and were lower among females (0.91, 95% CI 0.90 to 0.92, p<0.0001 compared with males). Costs were higher (1.09, 95% CI 1.01 to 1.14, p<0.0001) in London compared with other regions. CONCLUSIONS: Healthcare utilisation and costs in the last year of life increase with proximity to death, particularly in the last month of life. Finer geographical data and information on healthcare supply would allow further investigating whether people receiving more planned care by primary care and or specialist palliative care towards the end of life require less acute care.

Polymorphisms of SOCS-1 Are Associated With a Rapid HIV Progression Rate.

OBJECTIVES: Immune activation, among others driven by interferon (IFN)-α and IFN-γ activation, is a main feature of progressive HIV infection. Suppressor of cytokine signaling (SOCS) 1 and 3 are negative feedback regulators of the IFN-α and IFN-γ axis. Here, we analyzed the role of 9 single-nucleotide polymorphisms (SNPs) within SOCS-1 and SOCS-3 genes for their association with an HIV progression rate in a cohort of 318 rapid vs 376 slow progressors from the Swiss HIV Cohort Study. DESIGN AND METHODS: We analyzed 9 SNPs, which we have identified in Swiss blood donors, in a cohort of HIV-infected patients (n = 1144), which have been categorized according to the decline in CD4 T-cell counts. In all the conducted analyses, we focused on the comparison between rapid and slow progressors with regard to SNPs in SOCS-1 and SOCS-3 and with regard to haplotypes using multivariate logistic regression models. RESULTS: Three SOCS-1 SNPs (rs193779, rs33989964, and rs4780355) are associated with a risk reduction for rapid progression. Two of these SNPs, rs33989964 and rs4780355, are in strong linkage disequilibrium, forming a frequent haplotype. Homozygous carriers of this haplotype are also associated with a risk reduction for rapid progression. By contrast, the minor TT genotype of rs33977706 is associated with twice the risk for rapid progression. No associations have been observed for the 4 SOCS-3 SNPs or the major SOCS-3 haplotypes. CONCLUSIONS: Our data suggest that SNPs in SOCS-1 are associated with HIV disease progression and speak in favor that immune activation is causal for the progressive immunodeficiency.

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/µl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

Cost Estimates for Human Immunodeficiency Virus (HIV) Care and Patient Characteristics for Health Resource Use From Linkage of Claims Data With the Swiss HIV Cohort Study.

BACKGROUND: Comprehensive and representative data on resource use are critical for health policy decision making but often lacking for human immunodeficiency virus (HIV) infection. Privacy-preserving probabilistic record linkage of claim and cohort study data may overcome these limitations. METHODS: Encrypted dates of birth, sex, study center, and antiretroviral therapy (ART) from the Swiss HIV Cohort Study (SHCS) records for 2012 and 2013 were linked by privacy-preserving probabilistic record linkage with claim data from the largest health insurer covering 15% of the Swiss residential population. We modeled predictors for mean annual costs adjusting for censoring and grouped patients by cluster analysis into 3 risk groups for resource use. RESULTS: The matched subsample of 1196 patients from 9326 SHCS and 2355 claim records was representative for all SHCS patients receiving ART. The corrected mean (standard error) total costs in 2012 and 2013 were $30462 ($582) and $30965 ($629) and mainly accrued in ambulatory care for ART (70% of mean costs). The low-risk group for resource use had mean (standard error) annual costs of $26772 ($536) and $26132 ($589) in 2012 and 2013. In the moderate- and high-risk groups, annual costs for 2012 and 2013 were higher by $3526 (95% confidence interval, $1907-$5144) (13%) and $4327 ($2662-$5992) (17%) and $14026 ($8763-$19289) (52%) and $13567 ($8844-$18288) (52%), respectively. CONCLUSIONS: In a representative subsample of patients from linkage of SHCS and claim data, ART was the major cost factor, but patient profiling enabled identification of factors related to higher resource use.

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.

Socioeconomic and demographic inequalities in stage at diagnosis and survival among colorectal cancer patients: evidence from a Swiss population-based study.

Socioeconomic inequalities in cancer stage at diagnosis and survival are important public health issues. This study investigates the association between socioeconomic position (SEP) and colorectal cancer (CRC) stage at diagnosis and survival in Switzerland, a European country with highest level of medical facilities and life expectancy. We used population-based CRC data from seven Swiss cantonal cancer registries 2001-2008 (N = 10,088) linked to the Swiss National Cohort (SNC). Follow-up information was available until the end of 2013. SEP was estimated based on education. The association between cancer stage and SEP was assessed using logistic regression models including cancer localization (colon/rectum), sex, age, civil status, urbanity of residence, language region, and nationality (Swiss/non-Swiss). Survival was analyzed using competing risk regressions reporting subhazard ratios (SHRs) for the risk of dying due to CRC. We observed a social gradient for later stage CRC with adjusted odds ratios (ORs) of 1.11 (95% CI: 0.97-1.19) and 1.28 (95% CI: 1.08-1.50) for middle and low SEP compared to high SEP. Further, single compared to married people had elevated odds of being diagnosed at later stages. Survival was lower in patients with CRC with low SEP in the unadjusted model (SHR: 1.18, 95% CI: 1.07-1.30). After adjustment for stage at diagnosis and further sociodemographic characteristics, significant survival inequalities by SEP disappeared but remained for non-Swiss compared to Swiss citizens and for patients living in nonurban areas compared to their urban counterparts. Swiss public health strategies should facilitate equal access to CRC screening and optimal CRC care for all social groups and in all regions of Switzerland.

Trends and socioeconomic inequalities in amenable mortality in Switzerland with international comparisons.

BACKGROUND: Amenable mortality is a composite measure of deaths from conditions that might be avoided by timely and effective healthcare. It was developed as an indicator to study health care quality. METHODS: We calculated mortality rates for the population aged 0-74 years for the time-period 1996-2010 and the following groups of causes of death: amenable conditions, ischaemic heart diseases (IHD, defined as partly amenable) and remaining conditions. We compared the Swiss results with those published for 16 other high-income countries. To examine the association between amenable mortality and socioeconomic position, we calculated hazard ratios (HRs) by using Cox regression. RESULTS: Amenable mortality fell from 49.5 (95% confidence interval [CI] 48.2-51.0) to 35.7 (34.6-36.9) in males and from 55.0 (53.6-56.4) to 43.4 (42.2-44.6) per 100 000 person-years in females, when 1996-1998 was compared with 2008-2010. IHD mortality declined from 64.7 (95% CI 63.1-66.3) to 33.8 (32.8-34.8) in males and from 18.0 (17.2-18.7) to 8.5 (8.0-9.0) in females. However, between 1996-1998 and 2008-2010 the proportion of all-cause mortality attributed to amenable causes remained stable in both sexes (around 12% in males and 26% in females). Compared with 16 other high-income countries, Switzerland had the lowest rates of amenable mortality and ranked among the top five with the lowest ischaemic heart disease mortality. HRs of amenable causes in the lowest socioeconomic position quintile were 1.77 (95% CI 1.66-1.90) for males and 1.78 (1.47-2.16) for females compared with 1.62 (1.58-1.66) and 1.38 (1.33-1.43) for unamenable mortality. For ischaemic heart disease, HRs in the lowest socioeconomic position quintile were 1.76 (95% CI 1.66-1.87) for males and 2.33 (2.07-2.62) for females. CONCLUSIONS: Amenable mortality declined substantially in Switzerland with comparably low death rates for amenable causes. Similar to previous international studies, these Swiss results showed substantial socioeconomic inequalities in amenable mortality. Proportions of amenable mortality remained constant over time and patterns of inequalities observed for amenable causes in men did not substantially differ from those observed for non-amenable causes of death. Additional amenable mortality research is needed to better understand the factors contributing to mortality changes and social inequalities including information on disease characteristics and health care supply measures.

Socioeconomic and demographic disparities in breast cancer stage at presentation and survival: A Swiss population-based study.

We explored socioeconomic and demographic disparities in breast cancer (BC) stage at presentation and survival in a Swiss population-based sample of female BC patients linked to the census-based Swiss National Cohort. Tumor stage was classified according to Surveillance, Epidemiology and End Results Program summary stage (in situ/localized/regional/distant). We used highest education level attained to estimate SEP (low/middle/high). Further demographic characteristics of interest were age at presentation (30-49/50-69/70-84 years), living in a canton with organized screening (yes/no), urbanity of residence (urban/peri-urban/rural), civil status (single/married/widowed/divorced) and nationality (Swiss/non-Swiss). We used ordered logistic regression models to analyze factors associated with BC stage at presentation and competing risk regression models for factors associated with survival. Odds of later-stage BC were significantly increased for low SEP women (odds ratio 1.19, 95%CI 1.06-1.34) compared to women of high SEP. Further, women living in a canton without organized screening program, women diagnosed outside the targeted screening age and single/widowed/divorced women were more often diagnosed at later stages. Women of low SEP experienced an increased risk of dying from BC (sub-hazard ratio 1.22, 95%CI 1.05-1.43) compared to women of high SEP. Notably, these survival inequalities could not be explained by socioeconomic differences in stage at presentation and/or other sociodemographic factors. It is concerning that these social gradients have been observed in a country with universal health insurance coverage, high health expenditures and one of the highest life expectancies in the world.

Regional Variation of Cost of Care in the Last 12 Months of Life in Switzerland: Small-area Analysis Using Insurance Claims Data.

BACKGROUND: Health care spending increases sharply at the end of life. Little is known about variation of cost of end of life care between regions and the drivers of such variation. We studied small-area patterns of cost of care in the last year of life in Switzerland. METHODS: We used mandatory health insurance claims data of individuals who died between 2008 and 2010 to derive cost of care. We used multilevel regression models to estimate differences in costs across 564 regions of place of residence, nested within 71 hospital service areas. We examined to what extent variation was explained by characteristics of individuals and regions, including measures of health care supply. RESULTS: The study population consisted of 113,277 individuals. The mean cost of care during last year of life was 32.5k (thousand) Swiss Francs per person (SD=33.2k). Cost differed substantially between regions after adjustment for patient age, sex, and cause of death. Variance was reduced by 52%-95% when we added individual and regional characteristics, with a strong effect of language region. Measures of supply of care did not show associations with costs. Remaining between and within hospital service area variations were most pronounced for older females and least for younger individuals. CONCLUSIONS: In Switzerland, small-area analysis revealed variation of cost of care during the last year of life according to linguistic regions and unexplained regional differences for older women. Cultural factors contribute to the delivery and utilization of health care during the last months of life and should be considered by policy makers.

Kaposi Sarcoma Risk in HIV-Infected Children and Adolescents on Combination Antiretroviral Therapy From Sub-Saharan Africa, Europe, and Asia.

BACKGROUND: The burden of Kaposi sarcoma (KS) in human immunodeficiency virus (HIV)-infected children and adolescents on combination antiretroviral therapy (cART) has not been compared globally. METHODS: We analyzed cohort data from the International Epidemiologic Databases to Evaluate AIDS and the Collaboration of Observational HIV Epidemiological Research in Europe. We included HIV-infected children aged <16 years at cART initiation from 1996 onward. We used Cox models to calculate hazard ratios (HRs), adjusted for region and origin, sex, cART start year, age, and HIV/AIDS stage at cART initiation. RESULTS: We included 24 991 children from eastern Africa, southern Africa, Europe and Asia; 26 developed KS after starting cART. Incidence rates per 100 000 person-years (PYs) were 86 in eastern Africa (95% confidence interval [CI], 55-133), 11 in southern Africa (95% CI, 4-35), and 81 (95% CI, 26-252) in children of sub-Saharan African (SSA) origin in Europe. The KS incidence rates were 0/100 000 PYs in children of non-SSA origin in Europe (95% CI, 0-50) and in Asia (95% CI, 0-27). KS risk was lower in girls than in boys (adjusted HR [aHR], 0.3; 95% CI, .1-.9) and increased with age (10-15 vs 0-4 years; aHR, 3.4; 95% CI, 1.2-10.1) and advanced HIV/AIDS stage (CDC stage C vs A/B; aHR, 2.4; 95% CI, .8-7.3) at cART initiation. CONCLUSIONS: HIV-infected children from SSA but not those from other regions, have a high risk of developing KS after cART initiation. Early cART initiation in these children might reduce KS risk.

Socioeconomic disparities in childhood cancer survival in Switzerland.

In this study, we investigated whether childhood cancer survival in Switzerland is influenced by socioeconomic status (SES), and if disparities vary by type of cancer and definition of SES (parental education, living condition, area-based SES). Using Cox proportional hazards models, we analyzed 5-year cumulative mortality in all patients registered in the Swiss Childhood Cancer Registry diagnosed 1991-2006 below 16 years. Information on SES was extracted from the Swiss census by probabilistic record linkage. The study included 1602 children (33% with leukemia, 20% with lymphoma, 22% with central nervous system (CNS) tumors); with an overall 5-year survival of 77% (95%CI 75-79%). Higher SES, particularly parents' education, was associated with a lower 5-year cumulative mortality. Results varied by type of cancer with no association for leukemia and particularly strong effects for CNS tumor patients, where mortality hazard ratios for the different SES indicators, comparing the highest with the lowest group, ranged from 0.48 (95%CI: 0.28-0.81) to 0.71 (95%CI: 0.44-1.15). We conclude that even in Switzerland with a high quality health care system and mandatory health insurance, socioeconomic differences in childhood cancer survival persist. Factors causing these survival differences have to be further explored, to facilitate universal access to optimal treatment and finally eliminate social inequalities in childhood cancer survival.

Endothelial progenitor cells as a biological marker of peripheral artery disease.

The role of endothelial progenitor cells (EPCs) in peripheral artery disease (PAD) remains unclear. We hypothesized that EPC mobilization and function play a central role in the development of endothelial dysfunction and directly influence the degree of atherosclerotic burden in peripheral artery vessels. The number of circulating EPCs, defined as CD34(+)/KDR(+) cells, were assessed by flow cytometry in 91 subjects classified according to a predefined sample size of 31 non-diabetic PAD patients, 30 diabetic PAD patients, and 30 healthy volunteers. Both PAD groups had undergone endovascular treatment in the past. As a functional parameter, EPC colony-forming units were determined ex vivo. Apart from a broad laboratory analysis, a series of clinical measures using the ankle-brachial index (ABI), flow-mediated dilatation (FMD) and carotid intima-media thickness (cIMT) were investigated. A significant reduction of EPC counts and proliferation indices in both PAD groups compared to healthy subjects were observed. Low EPC number and pathological findings in the clinical assessment were strongly correlated to the group allocation. Multivariate statistical analysis revealed these findings to be independent predictors of disease appearance. Linear regression analysis showed the ABI to be a predictor of circulating EPC number (p=0.02). Moreover, the functionality of EPCs was correlated by linear regression (p=0.017) to cIMT. The influence of diabetes mellitus on EPCs in our study has to be considered marginal in already disease-affected patients. This study demonstrated that EPCs could predict the prevalence and severity of symptomatic PAD, with ABI as the determinant of the state of EPC populations in disease-affected groups.

Socioeconomic Status and Childhood Leukemia Incidence in Switzerland.

Socioeconomic status (SES) discrepancies exist for child and adult cancer morbidity and are a major public health concern. In this Swiss population-based matched case-control study on the etiology of childhood leukemia, we selected the cases from the Swiss Childhood Cancer Registry diagnosed since 1991 and the controls randomly from census. We assigned eight controls per case from the 1990 and 2000 census and matched them by the year of birth and gender. SES information for both cases and controls was obtained from census records by probabilistic record linkage. We investigated the association of SES with childhood leukemia in Switzerland, and explored whether it varied with different definitions of socioeconomic status (parental education, living condition, area-based SES), time period, and age. In conditional logistic regression analyses of 565 leukemia cases and 4433 controls, we found no consistent evidence for an association between SES and childhood leukemia. The odds ratio comparing the highest with the lowest SES category ranged from 0.95 (95% CI: 0.71-1.26; P trend = 0.73) for paternal education to 1.37 (1.00-1.89; P trend = 0.064) for maternal education. No effect modification was found for time period and age at diagnosis. Based on this population-based study, which avoided participation and reporting bias, we assume the potential association of socioeconomic status and childhood leukemia if existing to be small. This study did not find evidence that socioeconomic status, of Switzerland or comparable countries, is a relevant risk factor or strong confounder in etiological investigations on childhood leukemia.

Privacy preserving probabilistic record linkage (P3RL): a novel method for linking existing health-related data and maintaining participant confidentiality.

BACKGROUND: Record linkage of existing individual health care data is an efficient way to answer important epidemiological research questions. Reuse of individual health-related data faces several problems: Either a unique personal identifier, like social security number, is not available or non-unique person identifiable information, like names, are privacy protected and cannot be accessed. A solution to protect privacy in probabilistic record linkages is to encrypt these sensitive information. Unfortunately, encrypted hash codes of two names differ completely if the plain names differ only by a single character. Therefore, standard encryption methods cannot be applied. To overcome these challenges, we developed the Privacy Preserving Probabilistic Record Linkage (P3RL) method. METHODS: In this Privacy Preserving Probabilistic Record Linkage method we apply a three-party protocol, with two sites collecting individual data and an independent trusted linkage center as the third partner. Our method consists of three main steps: pre-processing, encryption and probabilistic record linkage. Data pre-processing and encryption are done at the sites by local personnel. To guarantee similar quality and format of variables and identical encryption procedure at each site, the linkage center generates semi-automated pre-processing and encryption templates. To retrieve information (i.e. data structure) for the creation of templates without ever accessing plain person identifiable information, we introduced a novel method of data masking. Sensitive string variables are encrypted using Bloom filters, which enables calculation of similarity coefficients. For date variables, we developed special encryption procedures to handle the most common date errors. The linkage center performs probabilistic record linkage with encrypted person identifiable information and plain non-sensitive variables. RESULTS: In this paper we describe step by step how to link existing health-related data using encryption methods to preserve privacy of persons in the study. CONCLUSION: Privacy Preserving Probabilistic Record linkage expands record linkage facilities in settings where a unique identifier is unavailable and/or regulations restrict access to the non-unique person identifiable information needed to link existing health-related data sets. Automated pre-processing and encryption fully protect sensitive information ensuring participant confidentiality. This method is suitable not just for epidemiological research but also for any setting with similar challenges.

Individual and spousal education, mortality and life expectancy in Switzerland: a national cohort study.

BACKGROUND: Household measures of socioeconomic position may better account for the shared nature of material resources, lifestyle, and social position of cohabiting persons, but household measures of education are rarely used. We aimed to evaluate the association of combined educational attainment of married couples on mortality and life expectancy in Switzerland. METHODS: The study included 3,496,163 ever-married persons aged ≥30 years. The 2000 census was linked to mortality records through 2008. Mortality by combined educational attainment was assessed by gender-age-specific HRs, with 95% CIs from adjusted models, life expectancy was derived using abridged life tables. RESULTS: Having a less educated partner was associated with increased mortality. For example, the HR comparing men aged 50-64 years with tertiary education married to women with tertiary education to men with compulsory education married to women with compulsory education was 2.05 (1.92-2.18). The estimated remaining life expectancy in tertiary educated men aged 30 years married to women with tertiary education was 4.6 years longer than in men with compulsory education married to women with compulsory education. The gradient based on individual education was less steep: the HR comparing men aged 50-64 years with tertiary education with men with compulsory education was 1.74 (1.67-1.81). CONCLUSIONS: Using individual educational attainment of married persons is common in epidemiological research, but may underestimate the combined effect of education on mortality and life expectancy. These findings are relevant to epidemiologic studies examining socio-demographic characteristics or aiming to adjust results for these characteristics.

Risk factors associated with the longevity of multi-rooted teeth. Long-term outcomes after active and supportive periodontal therapy.

AIM: To investigate risk factors for the loss of multi-rooted teeth (MRT) in subjects treated for periodontitis and enrolled in supportive periodontal therapy (SPT). MATERIAL AND METHODS: A total of 172 subjects were examined before (T0) and after active periodontal therapy (APT)(T1) and following a mean of 11.5 ± 5.2 (SD) years of SPT (T2). The association of risk factors with loss of MRT was analysed with multilevel logistic regression. The tooth was the unit of analysis. RESULTS: Furcation involvement (FI) = 1 before APT was not a risk factor for tooth loss compared with FI = 0 (p = 0.37). Between T0 and T2, MRT with FI = 2 (OR: 2.92, 95% CI: 1.68, 5.06, p = 0.0001) and FI = 3 (OR: 6.85, 95% CI: 3.40, 13.83, p < 0.0001) were at a significantly higher risk to be lost compared with those with FI = 0. During SPT, smokers lost significantly more MRT compared with non-smokers (OR: 2.37, 95% CI: 1.05, 5.35, p = 0.04). Non-smoking and compliant subjects with FI = 0/1 at T1 lost significantly less MRT during SPT compared with non-compliant smokers with FI = 2 (OR: 10.11, 95% CI: 2.91, 35.11, p < 0.0001) and FI = 3 (OR: 17.18, 95% CI: 4.98, 59.28, p < 0.0001) respectively. CONCLUSIONS: FI = 1 was not a risk factor for tooth loss compared with FI = 0. FI = 2/3, smoking and lack of compliance with regular SPT represented risk factors for the loss of MRT in subjects treated for periodontitis.

Impact of unlinked deaths and coding changes on mortality trends in the Swiss National Cohort.

BACKGROUND: Results of epidemiological studies linking census with mortality records may be affected by unlinked deaths and changes in cause of death classification. We examined these issues in the Swiss National Cohort (SNC). METHODS: The SNC is a longitudinal study of the entire Swiss population, based on the 1990 (6.8 million persons) and 2000 (7.3 million persons) censuses. Among 1,053,393 deaths recorded 1991-2007 5.4% could not be linked using stringent probabilistic linkage. We included the unlinked deaths using pragmatic linkages and compared mortality rates for selected causes with official mortality rates. We also examined the impact of the 1995 change in cause of death coding from version 8 (with some additional rules) to version 10 of the International Classification of Diseases (ICD), using Poisson regression models with restricted cubic splines. Finally, we compared results from Cox models including and excluding unlinked deaths of the association of education, marital status, and nationality with selected causes of death. RESULTS: SNC mortality rates underestimated all cause mortality by 9.6% (range 2.4%-17.9%) in the 85+ population. Underestimation was less pronounced in years nearer the censuses and in the 75-84 age group. After including 99.7% of unlinked deaths, annual all cause SNC mortality rates were reflecting official rates (relative difference between -1.4% and +1.8%). In the 85+ population the rates for prostate and breast cancer dropped, by 16% and 21% respectively, between 1994 and 1995 coincident with the change in cause of death coding policy. For suicide in males almost no change was observed. Hazard ratios were only negligibly affected by including the unlinked deaths. A sudden decrease in breast (21% less, 95% confidence interval: 12%-28%) and prostate (16% less, 95% confidence interval: 7%-23%) cancer mortality rates in the 85+ population coincided with the 1995 change in cause of death coding policy. CONCLUSIONS: Unlinked deaths bias analyses of absolute mortality rates downwards but have little effect on relative mortality. To describe time trends of cause-specific mortality in the SNC, accounting for the unlinked deaths and for the possible effect of change in death certificate coding was necessary.