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Objective One of the main goals of health examination surveys is to provide unbiased estimates of health indicators at the population level. We demonstrate how multiple imputation methods may help to reduce the selection bias if partial data on some nonparticipants are collected. Study Design and Setting In the FINRISK 2007 study, a population-based health study conducted in Finland, a random sample of 10,000 men and women aged 25–74 years were invited to participate. The study included a questionnaire data collection and a health examination. A total of 6,255 individuals participated in the study. Out of 3,745 nonparticipants, 473 returned a simplified questionnaire after a recontact. Both the participants and the nonparticipants were followed up for death and hospitalizations. The follow-up data allowed to check the assumptions on the missing data mechanism, and tailored multiple imputation methods were used to handle the missing data. Results Nonparticipation is a strong predictor for mortality in the five-year follow-up. However, the recontact response does not predict mortality or morbidity among the nonparticipants when adjusted for age and sex. The result suggests that the recontact respondents can be used as proxy for all nonparticipants. A comparison of raw estimates and estimates adjusted for selection bias reveals clear differences in the estimated population prevalences of smoking and heavy alcohol usage. Conclusion All efforts to collect data on nonparticipants are likely to be useful even if the response rate for the recontact remains low. Statistical analysis of the recontact respondents provides an indication of the extent of the selection bias, even in studies where follow-up data are not available to check the assumptions.
Aims: A common objective of epidemiological surveys is to provide population-level estimates of health indicators. Survey results tend to be biased under selective non-participation. One approach to bias reduction is to collect information about non-participants by contacting them again and asking them to fill in a questionnaire. This information is called recontact data, and it allows to adjust the estimates for non-participation. Methods: We analyse data from the FINRISK 2012 survey, where re-contact data were collected. We assume that the respondents of the recontact survey are similar to the remaining non-participants with respect to the health given their available background information. Validity of this assumption is evaluated based on the hospitalization data obtained through record linkage of survey data to the administrative registers. Using this assumption and multiple imputation, we estimate the prevalences of daily smoking and heavy alcohol consumption and compare them to es1 timates obtained with a commonly used assumption that the participants represent the entire target group. Results: This approach produces higher prevalence estimates than what is estimated from participants only. Among men, smoking prevalence estimate was 28.5% (23.2% for participants), heavy alcohol consumption prevalence was 9.4% (6.8% for participants). Among women, smoking prevalence was 19.0% (16.5% for participants) and heavy alcohol consumption 4.8% (3.0% for participants). Conclusion: Utilization of re-contact data is a useful method to adjust for non-participation bias on population estimates in epidemiological surveys.
Tässä diplomityössä pyritään luomaan ymmärrystä hankintatoimen ostoprosessien, kirjanpitoprosessien ja niitä tukevien IT- järjestelmien keskinäisistä riippuvuuksista. Tämän ymmärryksen avulla tavoitteena on mahdollistaa hankintatoimen tehokkuuden ja kannattavuusvaikutuksen mittaaminen kirjanpito- ja ostodatan avulla maailmanlaajuisesti toimivissa yrityksissä, joiden hankintatoimen organisaatio on hajautettu. Tämän diplomityön tutkimuskysymys on "kuinka mitata hankintatoimen tehokkuutta ja kannattavuusvaikutusta kirjanpito- ja ostodatan avulla?" Tutkimuskysymys on jaettu kahteen alakysymykseen: "mitä dataa täytyy kerätä operationaalisista IT- järjestelmistä hankintatoimen tehokkuuden kannattavuusvaikutuksen mittaamiseksi?", sekä "kuinka tämä data on strukturoitu eri operationaalisissa IT järjestelmissä?" Kirjallisuustutkimuksessa tarkastellaan aikaisempaa tutkimusta hankintatoimesta, hankintatoimen mittaamisesta sekä kannattavuusvaikutuksen mittaamisesta. Kirjallisuustutkimus osoittaa, että hankintatoimen tehokkuuden ja kannattavuusvaikutuksen mittaamiseen tarvittava tieto löytyy tyypillisesti kolmesta ostoprosessissa käytettävästä perusdokumentista: ostotilauksesta, tavaran vastaanottodokumentista ja laskusta. Teorian pohjalta tehtyjä tulkintoja testattiin kahden tapaustutkimuksen avulla. Kummassakin tapaustutkimuksessa arvioitiin asiakasyrityksen kahden toimipisteen hankintatoimen prosessit. Toimipisteet valittiin siten, että niissä oli käytössä keskenään erilaiset IT- järjestelmät. Eri toimipisteiden hankintatoimen prosesseja vertailtiin keskenään, tavoitteena löytää käytettyihin IT- järjestelmiin ja organisationaalisiin käytäntöihin sidoksissa olevia yhtenäisyyksiä ja poikkeavuuksia. Tapaustutkimus osoitti, että käytetyllä IT- järjestelmällä oli hyvin vähän vaikutusta hankintatoimen prosessien toimintaan. Tutkimuksessa ilmeni myös, että prosesseissa tallennettu tieto oli hankintatoimen tehokkuuden mittaamisen kannalta hyvin heikkolaatuista. Tämä johtuu siitä, että hankintatoimen prosessit olivat monelta osin määritelty hyvin huonosti, eivätkä siten tue hankintatoimen tehokkuuden mittausta erityisen hyvin.
Background Declining participation rates in health examination surveys may impair the representativeness of surveys and introduce bias into the comparison of results between population groups if participation rates differ between them. Changes in the characteristics of non-participants over time may also limit comparability with earlier surveys. Methods We studied the association of socio-economic position with participation, and its changes over the past 25 years. Occupational class and educational level are used as indicators of socio-economic position. Data from six cross-sectional FINRISK surveys conducted between 1987 and 2012 in Finland were linked to national administrative registers, which allowed investigation of the differences between survey participants and non-participants. Results Our results show that individuals with low occupational class or low level of education were less likely to participate than individuals with high occupational class or high level of education. Participation rates decreased in all subgroups of the population but the decline was fastest among those with low level of education. Conclusions The differences in participation rates must be taken into account to avoid biased estimates because socio-economic position has also been shown to be strongly related to health, health behaviour and biological risk factors. Particular attention should be paid to the recruitment of the less-educated population groups.
Abstract Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.
Tutkitun yrityksen hankintaosasto haluaa löytää ja valita sopivimmat toimittajat liiketoimintojen v alisille integraatioprojekteille (B2Bi), joissa toimittajan toiminnanohjausjärjestelmä (ERP) liitetään yrityksen oman ERP:n takajärjestelmään SAP Business Network digitaalisen hankintaekosysteemin (DSE) alustan kautta. Haasteena on löytää optimaalisimmat 10% 376:n suoran materiaalitoimittajan joukosta tähän tarkoitukseen ja priorisoida heidät asianmukaisella tavalla. Koska B2Bi-projektit vaativat suuren määrän aikaa, rahaa ja resursseja, valittujen toimittajien tulee täyttää useita kriteerejä tullakseen harkituiksi. Tutkimuksen tavoitteena on löytää ne edellytykset ja kriteerit, jotka tekevät toimittajasta sopivan, sekä tunnistaa haasteet, jotka voivat syntyä yhteisten prosessien linjaamiseksi. Tätä varten luodaan hyöty vs. vaiva kaksi-kertaa-kaksi -matriisi toimittajien vertailemiseksi, jotta voidaan selvittää, mikä aktivointistrategia toimii heille parhaiten. Tutkimus auttaa kyseistä yritystä laatimaan ihanteellisen toimittajan valintaprosessin ja aikataulun tuleville integraatioprojekteille ja toimii ennustetyökaluna yksittäisten toimittajien projektien kulun arvioinnissa. Aikaisemmin on rajoitetusti tutkittu toimittajan valintaprosessia, kriteereitä tai parhaita käytäntöjä integraation aikataulun optimoinnissa, jolloin tutkimus tuo rikastetun näkökulman rajatussa ympäristössä. Sen keskeisin panos on menetelmä, jonka avulla toimittajan valintalogiikkaa voidaan rakentaa useiden kriteerien ja tietojenkeruun kautta riskien vähentämiseksi sekä välttämättömien resurssien ja tietämyksen tunnistamiseksi onnistuneen strategisen projektin toteuttamiseksi.
Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5×10−6 in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5×10−6; 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8×10−3) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2×10−9). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2×10−3). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.
Abstract Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency ≤ 0.01) variant BP associations (P < 5 x 10(−8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
Abstract To dissect the genetic architecture of blood pressure and assess effects on target organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry, and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure–associated loci, of which 17 were new; 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target organ damage in multiple tissues but with minor effects in the kidney. Our findings expand current knowledge of blood pressure–related pathways and highlight tissues beyond the classical renal system in blood pressure regulation.
Abstract Background: Although high-density lipoprotein (HDL) and non-HDL cholesterol have opposite associations with coronary heart disease, multi-country reports of lipid trends only use total cholesterol (TC). Our aim was to compare trends in total, HDL and non-HDL cholesterol and the total-to-HDL cholesterol ratio in Asian and Western countries. Methods: We pooled 458 population-based studies with 82.1 million participants in 23 Asian and Western countries. We estimated changes in mean total, HDL and non-HDL cholesterol and mean total-to-HDL cholesterol ratio by country, sex and age group. Results: Since ∼1980, mean TC increased in Asian countries. In Japan and South Korea, the TC rise was due to rising HDL cholesterol, which increased by up to 0.17 mmol/L per decade in Japanese women; in China, it was due to rising non-HDL cholesterol. TC declined in Western countries, except in Polish men. The decline was largest in Finland and Norway, at ∼0.4 mmol/L per decade. The decline in TC in most Western countries was the net effect of an increase in HDL cholesterol and a decline in non-HDL cholesterol, with the HDL cholesterol increase largest in New Zealand and Switzerland. Mean total-to-HDL cholesterol ratio declined in Japan, South Korea and most Western countries, by as much as ∼0.7 per decade in Swiss men (equivalent to ∼26% decline in coronary heart disease risk per decade). The ratio increased in China. Conclusions: HDL cholesterol has risen and the total-to-HDL cholesterol ratio has declined in many Western countries, Japan and South Korea, with only a weak correlation with changes in TC or non-HDL cholesterol.
Abstract Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Abstract Background: Raised blood pressure is an important risk factor for cardiovascular diseases and chronic kidney disease. We estimated worldwide trends in mean systolic and mean diastolic blood pressure, and the prevalence of, and number of people with, raised blood pressure, defined as systolic blood pressure of 140 mm Hg or higher or diastolic blood pressure of 90 mm Hg or higher. Methods: For this analysis, we pooled national, subnational, or community population-based studies that had measured blood pressure in adults aged 18 years and older. We used a Bayesian hierarchical model to estimate trends from 1975 to 2015 in mean systolic and mean diastolic blood pressure, and the prevalence of raised blood pressure for 200 countries. We calculated the contributions of changes in prevalence versus population growth and ageing to the increase in the number of adults with raised blood pressure. Findings: We pooled 1479 studies that had measured the blood pressures of 19.1 million adults. Global age-standardised mean systolic blood pressure in 2015 was 127.0 mm Hg (95% credible interval 125.7–128.3) in men and 122.3 mm Hg (121.0–123.6) in women; age-standardised mean diastolic blood pressure was 78.7 mm Hg (77.9–79.5) for men and 76.7 mm Hg (75.9–77.6) for women. Global age-standardised prevalence of raised blood pressure was 24.1% (21.4–27.1) in men and 20.1% (17.8–22.5) in women in 2015. Mean systolic and mean diastolic blood pressure decreased substantially from 1975 to 2015 in high-income western and Asia Pacific countries, moving these countries from having some of the highest worldwide blood pressure in 1975 to the lowest in 2015. Mean blood pressure also decreased in women in central and eastern Europe, Latin America and the Caribbean, and, more recently, central Asia, Middle East, and north Africa, but the estimated trends in these super-regions had larger uncertainty than in high-income super-regions. By contrast, mean blood pressure might have increased in east and southeast Asia, south Asia, Oceania, and sub-Saharan Africa. In 2015, central and eastern Europe, sub-Saharan Africa, and south Asia had the highest blood pressure levels. Prevalence of raised blood pressure decreased in high-income and some middle-income countries; it remained unchanged elsewhere. The number of adults with raised blood pressure increased from 594 million in 1975 to 1.13 billion in 2015, with the increase largely in low-income and middle-income countries. The global increase in the number of adults with raised blood pressure is a net effect of increase due to population growth and ageing, and decrease due to declining age-specific prevalence. Interpretation: During the past four decades, the highest worldwide blood pressure levels have shifted from high-income countries to low-income countries in south Asia and sub-Saharan Africa due to opposite trends, while blood pressure has been persistently high in central and eastern Europe.
Abstract High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.