No description available.

The number of dementia cases is increasing worldwide. Most research and development in this area is related to the prevention of dementia, and to the development of various prediction tools for dementia. The tools made available take most of the medical data into account while calculating risk scores, with only a small amount of non-medical data. There is a lot of data related to medical and non-medical risk factors available from various sources which can be retrieved and analysed in real time, but this is today not used in any risk score tool for risk score calculation. As part of the project Multimodal strategies to promote a healthy brain in ageing: Innovative evidence-based tools (MULTI-MODE), a new risk score is being developed to be used in a new ICT-based tool for dementia prediction. Identification of non-medical data and a good model to fill the gap between data available at the server and using this data in risk score calculation may help in increasing the predictability of tools. In this thesis, some of the existing risk factors for the prediction of dementia are described, and the importance of non-medical factors in calculating risk scores is discussed. Additional non-medical factors are identified that could be included in future versions of the risk score. A database design for storing risk score information efficiently is presented, as is an app structure that can be used at the server side to validate the user input and to increase the effectiveness of a prediction tool. / Antal demensfall ökar över hela världen. Forskning och utveckling inom detta område är relaterat till att förebygga demens och att utveckla olika prognosverktyg för demens. Flera tillgängliga verktyg tar hänsyn till medicinska data i beräkning av riskpoäng, med endast en liten mängd av icke-medicinska data. Det finns en hel del data om medicinska och icke-medicinska faktorer online, men de används idag inte för riskpoängberäkning. Som en del av projektet Multimodala strategier för att främja en frisk hjärna i åldrande: Innovativa evidensbaserade verktyg (MULTI-MODE), så har en ny metod utvecklats för att användas i ett nytt IT-baserat verktyg för demensförutsägelse. Identifiering av icke-medicinska data och en bra modell för att överbrygga gapet mellan tillgängliga data på servern och använda dessa data i riskberäkning kan bidra till att öka precisionen hos verktyg. I den här studien beskrivs en del befintliga riskfaktorer för förutsägelse av demens och vikten av icke-medicinska faktorer i beräkning av risk diskuteras. Ytterligare icke-medicinska faktorer identifieras som skulle kunna ingå i framtida versioner av riskverktyg (såsom appar). Vissa identifierade riskfaktorer har analyserats och visade att effekten av att införa icke-medicinska faktorer ökar precisionen i resultaten. En databasdesign för lagring av riskinformation på ett effektivt sätt presenteras, liksom en appstruktur som kan användas på serversidan för att validera några av de parametrar som kan öka effektiviteten av verktyget.

Family-based and genome-wide association studies (GWAS) of alcohol dependence (AD) have reported numerous associated variants. The clinical validity of these variants for predicting AD compared to family history has not yet been reported. These studies aim to explore the aggregate impact of multiple genetic variants with small effect sizes on risk prediction in order to provide a clinical interpretation of genetic contributions to AD. Data simulations showed that given AD’s prevalence and heritability, a risk prediction model incorporating all genetic contributions would have an area under the receiver operating characteristic curve (AUC) approaching 0.80, which is often a target AUC for screening. Adding additional environmental factors could increase the AUC to 0.95. Using the Collaborative Study on the Genetics of Alcoholism (COGA) and the Study of Addiction: Genes and Environment (SAGE) GWAS samples, we used several different sources to capture genetic information associated with AD in discovery samples, and then tested genetic sum scores created based on this information for predictive accuracy in validation samples. Scores were assessed separately for single nucleotide polymorphisms (SNPs) associated in candidate gene studies and in GWAS analyses. Candidate gene sum scores did not exhibit significant predictive accuracy, but SNPs meeting less stringent p-value thresholds in GWAS analyses did, ranging from mean estimates of 0.549 for SNPs meeting p<0.01 to 0.565 for SNPs meeting p<0.50. Variants associated with subtypes of AD showed that there is similarly modest and significant predictive ability for an externalizing subtype. Scores created based on all individual SNP effects in aggregate across the entire genome accounted for 0.46%-0.57% of the variance in AD symptom count, and have AUCs of 0.527 to 0.549. Additional covariates and environmental factors that are correlated with AD increased the AUC to 0.865. Family history was a better classifier of case-control status than genetic sum scores, with an AUC of 0.686 in COGA and 0.614 in SAGE. This project suggests that SNPs from candidate gene studies and genome-wide association studies currently have limited clinical validity, but there is potential for enhanced predictive ability with better detection of genetic factors contributing to AD.

Les initiatives internationales pour l’accès au traitement antirétroviral (ARV) ont permis une réduction de la morbi-mortalité liée au VIH. Parallèlement, il existe croissance des risques cardio vasculaire (FRCV) dans les pays en développement, témoin d’une transition épidémiologique. Notre objectif était d’évaluer l’importance des FRCV avant et après mise sous antirétroviraux chez des personnes infectées par le VIH en Afrique. L’essai Temprano avait pour objectif d’évaluer les bénéfices et risque du traitement antirétroviral précoce et d’une chimio prophylaxie par 6 mois d’isoniazide (IPT) après 30 mois de suivi. Cette étude a conclu à l’efficacité des 2 interventions sur la réduction de la morbidité sévère, conduisant l’OMS, dès 2015, à recommander les ARV dès que les CD4 sont inférieurs à 500 CD4/mm3. Dans ce travail, nous avons évalué la prévalence des FRCV, et en particulier l’importance de l’obésité et du surpoids, à l’inclusion puis après 24 mois d’ARV. Nous avons ensuite calculé le score de risque cardio vasculaire selon l’équation de Framingham, avec et sans lipides à l’inclusion et à la fin du suivi. Il existait(i) une bonne corrélation des 2 équations (ii) une augmentation plus marquée du risque cardiovasculaire chez les femmes et (iii) une absence de différence de l’augmentation du risque selon les stratégies thérapeutiques. Enfin, dans le suivi long terme de Temprano nous montrons une efficacité de l’IPT sur la réduction de la mortalité, ce qui apporte un espoir dans un contexte où, malgré la transition épidémiologique en cours, les causes de mortalité sont toujours dominées par la Tuberculose en Afrique sub-saharienne. / The international initiatives for promoting access to antiretroviral therapy (ART) have reduced HIV- related morbidity and mortality. Meanwhile, there are growing cardiovascular risk factors (CVRF) in developing countries, which are witnessing an epidemiological transition. Our objective was to assess the significance of CVRF before and after initiating antiretroviral therapy in HIV-infected people in Africa. Temprano trial aimed to assess the benefits and risks of early antiretroviral therapy and 6-month isoniazid preventive therapy (IPT) after 30-month follow-up. This study concluded that both interventions are effective to reduce severe morbidity, what led WHO, in 2015, to recommend starting ART immediately if CD4 count drop below 500 cells / mm3. In this study, we assessed the prevalence of CVRF and the significance of obesity and overweight at baseline and after 24 months of ART in particular. We then assess the cardiovascular risk score according to the Framingham equation, with and without lipids, at baseline and at the end of follow-up. There were: (i) a positive correlation between the 2 equations (ii) a sharper increase in cardiovascular risks among women and (iii) no difference in the risk increase according to treatment strategies. Finally, in the long-term follow-up of Temprano trial, we are showing the efficacy of IPT on the reduction of mortality, which brings hope in a context where, despite the on-going epidemiological transition, the causes of deaths are still dominated by Tuberculosis in sub- Saharan Africa.

Abstract Type 2 diabetes can be prevented if the impaired glucose tolerance is found. Oral glucose tolerance test is needed in clinical practise for that but it is expensive and inconvenient. Obesity, hypertension, dyslipidemia and hypertension in pregnancy are factors often found in persons with type 2 diabetes. When there are more than one factor in same person the risk of type 2 diabetes multiplies. The purpose of this study was to investigate the prevalence of abnormal glucose metabolism and risk factors of type 2 diabetes in middle aged Finnish population in Savitaipale municipality and develop a method to screen abnormal glucose metabolism in primary health care. It was also studied the correlation of blood pressure and body mass index during pregnancy and abnormal glucose metabolism in later life. The study population was 1561 people born 1933–1956. 77,5% participated and 1097 people of them not having known abnormal glucose metabolism were taken to the cross-sectional study to develop the screening method. All 325 women who have had childbirth and files of that were taken to the prospective pregnancy cohort study. Information was collected with interview, measurements, laboratory research and from childbirth files. According the World Health Organisation criteria 1999 the prevalence of diabetes was 8,7% in men and 7,4% in women, previously undiagnosed 3,9% and 3,1%. Every fourth had abnormal glucose metabolism (men 23,2%, women 23,5%). The prevalence of obesity, hypertension, use of long-term antihypertensive medication and dyslipidemia (only in women) was higher among those, who had abnormal glucose metabolism. Logistic models were made for the classified risk factors. The model (AUC 0.718 for men, 0.761 for women) containing age, gender, waist circumference, systolic blood pressure and use of long-term antihypertensive medication was as good as model containing in addition family history of diabetes, smoking habits, serum lipids and long-term use of lipid lowering medication. Risk score tables were made from classified risk factors to evaluate the probability of the abnormal glucose metabolism. The blood pressure level and body mass index in pregnancy correlated independently with abnormal glucose metabolism in later life, blood pressure also adjusted with body mass index. Hypertension in pregnancy or after delivery correlated with abnormal glucose metabolism adjusted with body mass index. Hypertension in pregnancy doubled the risk of abnormal glucose metabolism in later life adjusted for body mass index in pregnancy and hypertension in later life. This information is important in prevention of type 2 diabetes. / Tiivistelmä Tyypin 2 diabetesta voidaan estää, mikäli heikentynyt glukoosinsieto tunnistetaan. Siihen tarvitaan glukoosirasituskoetta, jota on pidetty kalliina ja hankalana toteuttaa. Lihavuus, kohonnut verenpaine, dyslipidemia ja raskausdiabetes ovat tyypin 2 diabeteksen riskitekijöitä ja niiden ryvästyminen samaan henkilöön lisää diabetekseen sairastumisen todennäköisyyttä. Tyypin 2 diabeteksen riskitekijöiden ja poikkeavan glukoosiaineenvaihdunnan määrää ja raskauden aikaisen verenpaineen yhteyttä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan tutkittiin 1933–1956 syntyneessä savitaipalelaisessa väestössä. Tavoitteena oli kehittää perusterveydenhuoltoon soveltuva poikkeavan glukoosiaineenvaihdunnan seulontamenetelmä. Kohdejoukosta (n = 1561) osallistui 77,5 %, joista 1097:llä henkilöllä ei tiedetty olevan diabetesta. Heistä kerättiin tietoa haastattelulla, mittauksilla ja laboratoriotutkimuksilla sekä äitiysneuvolakorteista. Raskausaineistoon ja takenevaan kohorttitutkimukseen otettiin kaikki ne 325 naista, myös diabeetikot, joista raskaudesta oli tiedot käytettävissä. Diabetesta sairasti 8,7 % miehistä ja 7,4 % naisista, aiemmin diagnosoimattomia oli 3,9 % ja 3,1 %. Poikkeava glukoosiaineenvaihdunta oli joka neljännellä. Lihavuutta, kohonnutta verenpainetta, verenpainelääkkeen käyttöä ja naisilla dyslipidemiaa oli enemmän niillä, joilla oli poikkeava glukoosiaineenvaihdunta. Tutkimuksessa luotiin luokitelluista muuttujista logistisia malleja. Malli, johon muuttujiksi valittiin ikä, sukupuoli, vyötärön ympärys, systolinen verenpaine ja verenpainelääkkeen käyttö, todettiin yhtä hyväksi (miesten ROC -käyrän AUC 0.718, naisten 0.761) ennustamaan heikentynyt glukoosinsieto ja diabetes kuin malli, johon lisäksi valittiin suvun diabetes, tupakointi, rasva-arvoja ja lipidilääkityksen käyttö. Muuttujista tehtiin taulut, joista voi nähdä poikkeavan glukoosiaineenvaihdunnan todennäköisyyden. Raskauden aikainen verenpaine ja painoindeksi olivat yhteydessä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan, samoin loppuraskauden verenpaine painoindeksillä vakioituna. Raskaudessa todettu kohonnut verenpaine oli, mutta raskauden aiheuttama kohonnut verenpaine ei ollut, yhteydessä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan painoindeksistä riippumatta, samoin loppuraskauden diastolinen verenpaine seulonnan diastolisesta verenpaineesta riippumatta. Raskaudessa tai sen jälkeen todettu kohonnut verenpaine kaksinkertaisti poikkeavan glukoosiaineenvaihdunnan riskin loppuraskauden painoindeksistä tai seulonnassa todetusta kohonneesta verenpaineesta riippumatta. Kahdella helposti mitattavalla muuttujalla voidaan päätellä glukoosirasituskokeen tarve. Diabetesta ehkäistäessä on tärkeä tietää, että raskauden kohonnut verenpaine ja ylipaino lisäävät myöhempää poikkeavaa glukoosiaineenvaihduntaa.

Coronary heart disease (CHD) is one of the main causes of death in the world and Framingham Risk Score (FRS) is the most used tool to assess the risk of CHD in asymptomatic patients. However, it underestimates the cardiovascular (CDV) risk in some individuals. To address this problem, Brazilian Society of Cardiology proposes further risk stratification tests, using emerging risk factors - known as aggravating risk factors - that, when present, reclassify the risk category to a higher one than that initially estimated by the FRS. One does not know which of these aggravating risk factors have more influence in this reclassification, nor the frequency of each CDV risk category after their use and its financial cost. In an observational, descriptive study, 66 patients (54,8 ± 13,9 years, 33 men and 33 women) from a private clinic at Aracaju, Sergipe, had been evaluated during their routine medical exams. Forty three (65.2%) patients were at low-risk category and 23 (34.8%) at the intermediate risk. All of them had been submitted to the screening of the following aggravating risk factors: familiar history of premature CHD (FHCHD), metabolic syndrome (MS), left ventricular hypertrophy (LVH), high sensitivity C reactive protein (CPRus), chronic renal failure (CHF) and subclinical carotid atherosclerosis (SCA). Fifty seven individuals (86.4%) had presented some aggravating risk factors, and MS was the most frequent (68.2%), followed by LVH (34.9%), high CPRus (27.3%), SCA (25.8%), FHCHD (16.7%) and CHF (15.2%). After the reclassification, eight patients (12.1%) were of low risk, 36 (54.6%) of intermediate risk and 22 (33.3%) of high CDV risk. The combined diagnosis of MS and FHCHD was the less expensive strategy of reclassification, changing the risk of 48 patients (72.2%) with a cost of US$ 4,60 per each reclassified individual. The most expensive (US$ 327,52 each patient) was the isolated diagnostic of SCA, that changed the risk of only 17 patients (25.8%). Therefore, FRS underestimated CDV risk in the majority of the evaluated patients, because the frequency of risk enhancers was high, especially metabolic syndrome. Combined screening of the aggravating risk factors seems to be the better strategy. However, this screening must be individualized so as not to have unnecessary expenses. / A doença arterial coronariana (DAC) é uma das principais causas de morte no mundo e o Escore de Risco de Framingham (ERF) é uma das ferramentas mais utilizada para identificar indivíduos assintomáticos predispostos a essa patologia. Entretanto, ele subestima o risco cardiovascular (CDV) em determinados pacientes. Para contornar esse problema, a Sociedade Brasileira de Cardiologia preconiza a pesquisa de algumas variáveis clínicas e laboratoriais - conhecidas como critérios agravantes de risco que, quando presentes, reclassificam os pacientes numa categoria de risco superior aquela inicialmente estimada pelo ERF. Não se sabe quais dos critérios agravantes propostos têm maior influência nessa reclassificação, a freqüência de cada faixa de risco CDV nem o custo financeiro após a utilização desses agravantes. Trata-se de um estudo observacional, descritivo, foram avaliados 66 indivíduos com idade média de 54,8 ± 13,9 anos, atendidos em um serviço privado de Aracaju, Sergipe, para check-up cardiológico rotineiro. Eram 43 (65,2%) pacientes de baixo e 23 (34,8%) de médio risco pelo ERF, sendo 33 homens e 33 mulheres. Todos foram submetidos à pesquisa dos seguintes critérios agravantes: história familiar de DAC precoce (HFDAC), síndrome metabólica (SM), hipertrofia ventricular esquerda (HVE), proteína C reativa de alta sensibilidade elevada (PCRas), insuficiência renal crônica (IRC) e aterosclerose subclínica de carótidas (ATCL). Cinqüenta e sete indivíduos (86,4%) apresentaram algum agravante de risco, sendo a SM o mais frequente (68,2%), seguida pela HVE (34,9%), PCRas elevada (27,3%), ATCL (25,8%), HFDAC (16,7%) e IRC (15,2%). Após a reclassificação, oito pacientes (12,1%) eram de baixo risco, 36 (54,6%) de médio risco e 22 (33,3%) de alto risco CDV. A pesquisa combinada de SM e HFDAC foi a estratégia mais barata de reestratificação, mudando o risco de 48 pacientes (72,2%) a um custo de US$ 4,60 por indivíduo reclassificado. A mais cara (US$ 327,52 por paciente) foi a investigação isolada de ATCL, que mudou a categoria do risco em apenas 17 pessoas (25,8%). Em suma, o ERF subestimou o risco CDV na maioria dos pacientes estudados devido à elevada freqüência de critérios agravantes. Todavia, a solicitação de exames deve ser criteriosa para que não haja gastos desnecessários. A pesquisa combinada de SM e HFDAC foi a estratégia com melhor relação custo benefício.

Cardiovascular diseases (CVD) are responsible for more deaths than any other disease, continue to threaten the quality of life for many, and is a major burden to the health care system. The Framingham Heart Study (FHS) identified the major CVD risk factors that became essential to effective CVD screening strategies and the Framingham Risk Score (FRS), is used to assess CVD risk. Based on the concepts of the health behavior model and CVD as a cardiometabolic disorder, multivariate logistic regression analysis was used to evaluate the association between fasting blood glucose (FBG) levels and a CHD event, and to determine the value of FBG replacing a diagnosis of diabetes (DM2) in the FRS. The data set consisted of the 2,677 subjects of the FHS III cohort. In the univariate analysis, both DM2 and FBG were statistically significant (both p =.000), but the association was stronger for DM2, b = 2.138, OR = 8.483 (95% CI: 4.229, 17.105) than for FBG, b = .015, p = .000, OR=1.015 (95% CI: 1.009, 1.022). When adjusted for age, blood pressure, cholesterol, and smoking status, only DM2 remained statistically significant, OR = 2.295, p = .041, (95% CI: 1.035, 5.087) in the model. The FBG version of the FRS did not provide any improvement in performance, as it was marginally inferior to the DM2 version. Furthermore, the interactions between FBG and the metabolic risk factors were not statistically significant for this given data set. The results imply that a diagnosis of diabetes remains the factor of choice for inclusion in the FRS model for predicting the 10-year risk of CHD and replacing it with FBG provides little to no practical benefit. These findings support the use of CVD risk factor reduction and the use of effective screening tools in CVD prevention and promotion heart health.

Coronary heart disease, an inflammatory disease, is the leading cause of death globally. White blood cell counts (including monocytes) are easily available biomarkers of systemic inflammation. Monocyte subtypes can be measured by flow cytometry and classified into classical (CD14high, CD16neg), intermediate (CD14high, CD16+) and non-classical (CD14+, CD16high) with distinct functional properties. The goal of this study was to investigate the association of monocyte total count and its subtypes with cardiovascular risk groups defined by the Framingham Risk Score, which is used to estimate the 10-year risk of developing myocardial infarction or predict mortality following coronary heart disease. We also aimed to investigate whether monocyte counts are associated with relevant cardiovascular risk factors not included in the Framingham Risk Score, such as carotid atherosclerotic plaque and intima-media thickness. Our data came from the LIFE-Adult study, a population-based cohort study of 10,000 randomly selected participants in Leipzig, Germany. Data was gathered using self-administered questionnaires and physical examinations. Carotid plaques and intima-media thickness were measured using carotid artery sonography. Monocyte subtypes in blood were determined by 10-color flow cytometry for a total of 690 individuals. In a multivariate regression analysis adjusting for the risk factors BMI, intima-media thickness, presence of carotid plaques and diabetes mellitus, monocyte subtypes and total count were found to be significantly associated with the dichotomized Framingham Risk Score (≥10% versus <10%): Odds ratios [95% confidence interval] for monocyte subtypes: classical: 11.19 [3.79–34.26]; intermediate: 2.27 [1.11–4.71]; non-classical: 4.18 [1.75–10.20]; total: 14.59 [4.61–47.95]. In absence of prospective data, the FRS was used as a surrogate for CHD. Our results indicate that monocyte counts could provide useful predictive value for cardiovascular disease risk.

No description available.

Yes / Objectives: To develop a logistic regression model to predict the risk of sepsis following emergency medical admission using the patient’s first, routinely collected, electronically recorded vital signs and blood test results and to validate this novel computer-aided risk of sepsis model, using data from another hospital. Design: Cross-sectional model development and external validation study reporting the C-statistic based on a validated optimized algorithm to identify sepsis and severe sepsis (including septic shock) from administrative hospital databases using International Classification of Diseases, 10th Edition, codes. Setting: Two acute hospitals (York Hospital - development data; Northern Lincolnshire and Goole Hospital - external validation data). Patients: Adult emergency medical admissions discharged over a 24-month period with vital signs and blood test results recorded at admission. Interventions: None. Main Results: The prevalence of sepsis and severe sepsis was lower in York Hospital (18.5% = 4,861/2,6247; 5.3% = 1,387/2,6247) than Northern Lincolnshire and Goole Hospital (25.1% = 7,773/30,996; 9.2% = 2,864/30,996). The mortality for sepsis (York Hospital: 14.5% = 704/4,861; Northern Lincolnshire and Goole Hospital: 11.6% = 899/7,773) was lower than the mortality for severe sepsis (York Hospital: 29.0% = 402/1,387; Northern Lincolnshire and Goole Hospital: 21.4% = 612/2,864). The C-statistic for computer-aided risk of sepsis in York Hospital (all sepsis 0.78; sepsis: 0.73; severe sepsis: 0.80) was similar in an external hospital setting (Northern Lincolnshire and Goole Hospital: all sepsis 0.79; sepsis: 0.70; severe sepsis: 0.81). A cutoff value of 0.2 gives reasonable performance. Conclusions: We have developed a novel, externally validated computer-aided risk of sepsis, with reasonably good performance for estimating the risk of sepsis for emergency medical admissions using the patient’s first, electronically recorded, vital signs and blood tests results. Since computer-aided risk of sepsis places no additional data collection burden on clinicians and is automated, it may now be carefully introduced and evaluated in hospitals with sufficient informatics infrastructure. / Health Foundation