The Secure Anonymised Information Linkage databank Dementia e-cohort (SAIL-DeC).

INTRODUCTION: The rising burden of dementia is a global concern, and there is a need to study its causes, natural history and outcomes. The Secure Anonymised Information Linkage (SAIL) Databank contains anonymised, routinely-collected healthcare data for the population of Wales, UK. It has potential to be a valuable resource for dementia research owing to its size, long follow-up time and prospective collection of data during clinical care. OBJECTIVES: We aimed to apply reproducible methods to create the SAIL dementia e-cohort (SAIL-DeC). We created SAIL-DeC with a view to maximising its utility for a broad range of research questions whilst minimising duplication of effort for researchers. METHODS: SAIL contains individual-level, linked primary care, hospital admission, mortality and demographic data. Data are currently available until 2018 and future updates will extend participant follow-up time. We included participants who were born between 1st January 1900 and 1st January 1958 and for whom primary care data were available. We applied algorithms consisting of International Classification of Diseases (versions 9 and 10) and Read (version 2) codes to identify participants with and without all-cause dementia and dementia subtypes. We also created derived variables for comorbidities and risk factors. RESULTS: From 4.4 million unique participants in SAIL, 1.2 million met the cohort inclusion criteria, resulting in 18.8 million person-years of follow-up. Of these, 129,650 (10%) developed all-cause dementia, with 77,978 (60%) having dementia subtype codes. Alzheimer's disease was the most common subtype diagnosis (62%). Among the dementia cases, the median duration of observation time was 14 years. CONCLUSION: We have created a generalisable, national dementia e-cohort, aimed at facilitating epidemiological dementia research.

Matched population-based study examining the risk of type 2 diabetes in people with and without diagnosed hepatitis C virus infection.

Meta-analyses have found hepatitis C virus (HCV) infection to be associated with an increased risk of type 2 diabetes mellitus (T2DM). Here, we examine this association within a large population-based study, according to HCV RNA status. A data-linkage approach was used to examine the excess risk of diagnosed T2DM in people diagnosed with antibodies to HCV (anti-HCV) in Scotland (21 929 anti-HCV(+ves) ; involving 15 827 HCV RNA(+ves) , 3927 HCV RNA(-ves) and 2175 with unknown RNA-status) compared to that of a threefold larger general population sample matched for gender, age and postcode (65 074 anti-HCV(-ves) ). To investigate effects of ascertainment bias the following periods were studied: up to 1 year before (pre-HCV)/within 1 year of (peri-HCV)/more than 1 year post (post-HCV) the date of HCV-diagnosis. T2DM had been diagnosed in 2.9% of anti-HCV(+ves) (including 3.2% of HCV RNA(+ves) and 2.3% of HCV RNA(-ves) ) and 2.7% of anti-HCV(-ves) . A higher proportion of T2DM was diagnosed in the peri-HCV period (i.e. around the time of HCV-diagnosis) for the anti-HCV(+ves) (22%) compared to anti-HCV(-ves) (10%). In both the pre-HCV and post-HCV periods, only those anti-HCV(+ves) living in less deprived areas (13% of the cohort) were found to have a significant excess risk of T2DM compared to anti-HCV(-ves) (adjusted odds ratio in the pre-HCV period: 4.0 for females and 2.3 for males; adjusted hazard ratio in the post-HCV period: 1.5). These findings were similarly observed for both HCV RNA(+ves) (chronic) and HCV RNA(-ves) (resolved). In the largest study of T2DM among chronic HCV-infected individuals to date, there was no evidence to indicate that infection conveyed an appreciable excess risk of T2DM at the population level.

Use of laboratory-based surveillance data to estimate the number of people chronically infected with hepatitis B living in Scotland.

It is paramount to understand the epidemiology of chronic hepatitis B to inform national policies on vaccination and screening/testing as well as cost-effectiveness studies. However, information on the national (Scottish) prevalence of chronic hepatitis B by ethnic group is lacking. To estimate the number of people with chronic hepatitis B in Scotland in 2009 by ethnicity, gender and age, the test data from virology laboratories in the four largest cities in Scotland were combined with estimates of the ethnic distribution of the Scottish population. Ethnicity in both the test data and the Scottish population was derived using a name-based ethnicity classification software (OnoMAP; Publicprofiler Ltd, UK). For 2009, we estimated 8720 [95% confidence interval (CI) 7490-10 230] people aged ⩾15 years were living with chronic hepatitis B infection in Scotland. This corresponds to 0·2% (95% CI 0·17-0·24) of the Scottish population aged ⩾15 years. Although East and South Asians make up a small proportion of the Scottish population, they make up 44% of the infected population. In addition, 75% of those infected were aged 15-44 years with almost 60% male. This study quantifies for the first time on a national level the burden of chronic hepatitis B infection by ethnicity, gender and age. It confirms the importance of promoting and targeting ethnic minority groups for hepatitis B testing.

Estimating the number of injecting drug users in Scotland's HCV-diagnosed population using capture-recapture methods.

In countries maintaining national hepatitis C virus (HCV) surveillance systems, a substantial proportion of individuals report no risk factors for infection. Our goal was to estimate the proportion of diagnosed HCV antibody-positive persons in Scotland (1991-2010) who probably acquired infection through injecting drug use (IDU), by combining data on IDU risk from four linked data sources using log-linear capture-recapture methods. Of 25,521 HCV-diagnosed individuals, 14,836 (58%) reported IDU risk with their HCV diagnosis. Log-linear modelling estimated a further 2484 HCV-diagnosed individuals with IDU risk, giving an estimated prevalence of 83. Stratified analyses indicated variation across birth cohort, with estimated prevalence as low as 49% in persons born before 1960 and greater than 90% for those born since 1960. These findings provide public-health professionals with a more complete profile of Scotland's HCV-infected population in terms of transmission route, which is essential for targeting educational, prevention and treatment interventions.

Comparison of the breeding performance of cows in cold and warm loose-housing systems in Finland.

Finland's cold loose-housing systems for dairy cows were compared with the more traditional warm loose-housing systems regarding the number of days from calving-to-first-service, the first-service-pregnancy risk and the repeated-service-conception hazard. 3131 calvings registered during the indoor periods in 1996 and 1997 on 208 farms were modelled using multilevel survival analysis and logistic regression in a retrospective cohort study. Compared to cows in a warm loose-housing system, cows in a cold loose-housing system had the same period from calving-to-first-service, a significant 6% lower first-service-pregnancy risk and the same repeated-service-conception hazard.

Comparison of the disease incidences of Finnish Ayrshire and Finnish Black and White dairy cows.

Finnish Ayrshire and Finnish Black and White cows were compared regarding the incidences of early and late mastitis, parturient paresis, ketosis, ovarian disorders, metritis and the risk of having a test-day somatic-cell count >200,000 cells ml(-1) at any of the first three monthly test days in lactation. In a retrospective cohort study 101,793 cows from 5844 tie stalls and 11,811 cows from 437 loose-housing systems from all over Finland were followed from calving in 2000 until the end of lactation. The observed incidences of those cows were then analysed using generalised linear mixed models. Finnish Black and White cows had higher incidences of all diseases except ovarian disorders. Although the differences were statistically significant in all models except metritis and early mastitis in loose-housing systems, they were, in our view, only important on the national level (for the breeding organisations), and of little importance for the farmers.

Comparison of milk production of dairy cows kept in cold and warm loose-housing systems.

A retrospective cohort study was conducted to test whether the lactation curves of cows kept in cold loose-housing systems (CLHs) were the same as for cows in warm loose-housing systems (WLHs) in the Nordic countries. Approximately 40000 test-day records from 5366 Ayrshire or Black and White cows kept on 38 CLHs and 166 WLHs in Finland during 1996 and 1997 were used. Analysis used a random-coefficient model (correcting for parity, breed and calving-year-season and the correlation-structure between test-days of the same cow and cows of the same herd). Cows in a CLH produced up to 1l less milk per test-day, but this difference was not statistically significant. Surprisingly, the difference in milk yield was not affected by calving-year-season, parity or breed.

Comparison of the disease incidences of dairy cows kept in cold and warm loose-housing systems.

Finland's cold loose-housing systems for dairy cows were compared with the more traditional warm loose-housing systems regarding the incidences of ketosis, mastitis, metritis, parturient paresis and ovarian disorders. Approximately 5000 calvings on 210 farms during the years 1996 and 1997 were modelled, using multilevel Poisson regression and multilevel logistic-regression in a retrospective observational cohort study. Cows in a cold loose-housing system were at lower odds for developing late mastitis (15-305 days in milk), and metritis (Friesian breed); of the same odds for ketosis and early mastitis (0-14 days in milk); but at higher odds for developing parturient paresis and metritis (Ayrshire breed). The estimated odds ratio for ovarian disorders depended on the definition for exposure. Although one of the differences was statistically significant and many of them of veterinary interest, none of them appear to be substantial for the economy of a median-sized dairy farm in Finland.

Radiolabelling of parenteral O/W emulsions by means of neutron activation.

Parenteral O/W emulsions containing lanthanide fatty acid derivatives were prepared. With regard to enhancing the incorporation efficiency of the neutron activatable excipients, the addition of the non-ionic co-emulsifier Solutol HS 15 proved to be most suitable. Comparing the different chain lengths of the fatty acids, the long chain fatty acid derivative lanthanide(tri)stearate seemed to be superior in strengthening the interfacial layer. After neutron activation, the physical and chemical stability of the irradiated formulations was evaluated. The chemical stability, indicated by the concentration of lyso phosphatidylcholine as the degradation product of the main emulsifier, was shown to be dependent on the irradiation time. By applying a neutron flux of 2.1 x 10(13) neutrons/cm2 per s, the maximum should not rise above 60 s. The physical stability indicated by the particle size distribution was affected by the presence of the non-ionic co-emulsifier. Concerning the amount of radiation necessary for in vivo biodistribution studies the maximum load of Samarium fatty acid derivatives did not yield sufficient radioactivity levels. However, Europium derivatives could be shown to be suitable for in vivo studies.

[Biliary, renal and fecal elimination and distribution of gold after a single oral administration of auranofin, quantified by the instrumental neutron activation analysis method]. / Biliäre, renale und fäkale Elimination und Verteilung von Gold nach einmaliger oraler Gabe von Auranofin, quantifiziert mit der Methode der instrumentellen Neutronenaktivierungsanalyse (INAA).

Three days after cholecystectomy, seven patients received a single dose of auranofin (5 tablets Ridaura = 4.35 mg gold). At defined time points thereafter the gold content in samples of blood, plasma, urine, bile, and feces was determined by instrumental neutron activation analysis (INAA). Maxima of the mean gold concentrations in blood (140 +/- 42 ng/ml) and plasma (173 +/- 54 ng/ml) are found 2 h after oral administration of the antirheumatic agent, after 16 h in urine (43 +/- 28 ng/ml) and bile (65 +/- 50 ng/ml), and after 24 h in erythrocytes (greater than 200 ng/ml). The mean terminal half-lives are 7.6 days (blood), 15 days (plasma), 5 days (erythrocytes), and 6.5 days (bile). The cumulative biliary gold excretion within 8 days after the administration of auranofin was 1.6%, compared with 4% and 40% for renal and fecal elimination, respectively. The gold concentration in plasma is always higher than that in bile. There is a close correlation between the areas under the concentration curves (AUC) in bile and plasma (r = 0.864).

Whole body elimination routes of gold in humans after a single-dose application of the antirheumatic auranofin.

After removal of the gallbladder (cholecystectomy) 7 patients were administered the antirheumatic agent Auranofin in its commercially available tablet form (Ridaura) 3 d postoperative. The single dose consisted of 5 tablets (4.35 mg of gold). Gold was determined in samples of blood, plasma, urine, bile, and feces (1-2 mL and 2.5 g, respectively). The specimens were drawn 10 min to 8 d p.a. and on d 14 p.a. The determinations were performed by instrumental neutron activation analysis (INAA). The limit of detection was less than 1 ng of gold. The courses of the mean gold concentrations show maxima after 1.9 h in blood and plasma, and after 16 h in urine and bile. The mean half-lives (terminal phases) are 7.6 d (blood), 23 d (plasma), and 6.5 d (bile).

Pharmacokinetics of auranofin a single dose study in man.

Three days after cholecystectomy 7 patients were given a single dose of auranofin (5 tablets Ridaura = 4.35 mg gold). Gold was detected in samples of blood, plasma, urine, bile and feces. The determinations were carried out using instrumental neutron activation analysis. The mean gold concentrations reached maximum in blood and plasma after 2 h and in urine and bile after 16 h. The mean terminal half-lives were 7.6 days (blood), 15 days (plasma) and 6.5 days (bile). Cumulative amounts of gold excreted in bile, urine, and feces were 1.6, 4 and 40%, respectively.